|
1
|
Reichmann R, Nimptsch K, Pischon T, Gunter MJ, Jenab M, Eriksen AK, Tjonneland A, Janke J, Katzke V, Kaaks R, Schulze MB, Eichelmann F, Masala G, Sieri S, Pasanisi F, Tumino R, Giraudo MT, Rothwell J, Severi G, Jakszyn P, Sanchez-Perez MJ, Amiano P, Colorado-Yohar SM, Guevara M, van Guelpen B, Aglago EK, Heath AK, Smith-Byrne K, Weiderpass E, Aleksandrova K. Sex- and site-specific associations of circulating lipocalin 2 and incident colorectal cancer: Results from the EPIC cohort. Int J Cancer 2025; 156:930-942. [PMID: 39511728 DOI: 10.1002/ijc.35205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2024] [Revised: 07/17/2024] [Accepted: 07/18/2024] [Indexed: 11/15/2024]
Abstract
Experimental research has uncovered lipocalin 2 (LCN2) as a novel biomarker implicated in the modulation of intestinal inflammation, metabolic homeostasis, and colon carcinogenesis. However, evidence from human research has been scant. We, therefore, explored the association of pre-diagnostic circulating LCN2 concentrations with incident colorectal cancer (CRC) in a nested case-control study within the in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. LCN2 was measured in 1267 incident CRC cases matched to 1267 controls using incidence density sampling. Conditional logistic regression was used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95% CIs) according to tumor subsite and sex. Weighted Cox proportional hazard regression was used to explore associations by adiposity status. In multivariable-adjusted analyses, the IRR [95% CI] per doubling in LCN2 concentration was 1.16 [0.98-1.37] for CRC overall, 1.26 [1.00-1.59] for colon cancer, and 1.08 [0.85-1.38] for rectal cancer. The association for colon cancer was more pronounced in women (IRR [95% CI], 1.66 [1.20-2.30]) and for proximal colon cancer (IRR [95% CI], 1.96 [1.15-3.34]), whereas no association was seen in men and distal colon cancer. The association for colon cancer was positive in individuals with high waist circumference (hazard ratio [95% CI], 1.69 [1.52-1.88]) and inverse in individuals with low waist circumference (hazard ratio [95% CI], 0.86 [0.76-0.98], P interaction<0.01). Overall, these data suggest that pre-diagnostic LCN2 concentrations were positively associated with colon cancer, particularly occurring in the proximal colon, in women and among individuals with abdominal adiposity.
Collapse
Grants
- Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands)
- German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany)
- Danish Cancer Society (Denmark)
- Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France)
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London
- 001 World Health Organization
- Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy)
- International Agency for Research on Cancer (IARC)
- Cancer Research UK (14,136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1,000,143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom).
- Health Research Fund (FIS)-Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology-ICO (Spain)
- Swedish Cancer Society, Swedish Research Council, Region Skåne and Region Västerbotten (Sweden)
Collapse
Affiliation(s)
- Robin Reichmann
- Biomarkers and Metabolism Research Group, Department of Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology, Bremen, Germany
| | - Katharina Nimptsch
- Molecular Epidemiology Research Group, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- Biobank Technology Platform, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
| | - Tobias Pischon
- Molecular Epidemiology Research Group, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- Biobank Technology Platform, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- Core Facility Biobank, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Marc J Gunter
- International Agency for Research on Cancer, World Health Organization, Lyon, France
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Mazda Jenab
- International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Anne Kirstine Eriksen
- Diet, Cancer and Health Research Group, Danish Cancer Institute, Danish Cancer Society, Copenhagen, Denmark
| | - Anne Tjonneland
- Diet, Cancer and Health Research Group, Danish Cancer Institute, Danish Cancer Society, Copenhagen, Denmark
- Department of Public Health, University of Copenhagen, Copenhagen, Denmark
| | - Jürgen Janke
- Molecular Epidemiology Research Group, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- Biobank Technology Platform, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
| | - Verena Katzke
- Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Rudolf Kaaks
- Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Matthias B Schulze
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
- Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Fabian Eichelmann
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Giovanna Masala
- Prevention and Clinical Network, Institute for the Study and Prevention of Cancer (ISPRO), Florenz, Italy
| | - Sabina Sieri
- Epidemiology and Prevention Unit, Fondazione IRCCS Instituto Nazionale dei Tumori, Milan, Italy
| | - Fabrizio Pasanisi
- Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
| | - Rosario Tumino
- Hyblean Association for Epidemiological Research, Associazione Iblea per la Ricerca Epidemiologica (A.I.R.E.-ONLUS), Ragusa, Italy
| | - Maria Teresa Giraudo
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Joseph Rothwell
- CESP-Univ. Paris-Saclay, UVSQ, Inserm-"Exposome, heredity, cancer and health" Team, The Centre for Research in Epidemiology and Population Health, Villejuif, France
| | - Gianluca Severi
- CESP-Univ. Paris-Saclay, UVSQ, Inserm-"Exposome, heredity, cancer and health" Team, The Centre for Research in Epidemiology and Population Health, Villejuif, France
- Department of Statistics, Computer Science, Applications "G. Parenti" (DISIA), University of Florence, Florence, Italy
| | - Paula Jakszyn
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain
- Blanquerna School of Health Sciences, Ramon Llull University, Barcelona, Spain
| | - Maria Jose Sanchez-Perez
- CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Public Health Research and Health Services Research Group, Andalusian School of Public Health (EASP), Granada, Andalucía, Spain
- Epidemiology, Prevention and Control of Cancer Research Group, Biosanitary Research Institute of Granada (ibs.Granada), Granada, Spain
- Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain
| | - Pilar Amiano
- Sub Directorate for Public Health and Addictions of Gipuzkoa, Ministry of Health of the Basque Government, San Sebastian, Spain
- Epidemiology of Chronic and Communicable Diseases Group, Biodonostia Health Research Institute, San Sebastian, Spain
- Instituto de Salud Carlos III, CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
| | - Sandra M Colorado-Yohar
- Department of Epidemiology, Murcia Regional Health Council, Instituto Murciano de Investigación Biosanitaria, Murcia, Spain
- Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellin, Colombia
| | - Marcela Guevara
- CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Epidemiology and Health Prevention Service, Institute of Public Health and Labor of Navarre, Pamplona, Navarra, Spain
- Epidemiology of Cancer and Other Chronic Diseases Research Group, Healthcare Research Institute of Navarre (IdiSNA), Pamplona, Spain
| | - Bethany van Guelpen
- Department of Radiation Sciences, Umeå University, Umeå, Sweden
- Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden
| | - Elom K Aglago
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Alicia K Heath
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Karl Smith-Byrne
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Elisabete Weiderpass
- International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Krasimira Aleksandrova
- Biomarkers and Metabolism Research Group, Department of Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology, Bremen, Germany
- Faculty of Human and Health Sciences, University of Bremen, Bremen, Germany
| |
Collapse
|
|
2
|
González-Gil EM, Peruchet-Noray L, Sedlmeier AM, Christakoudi S, Biessy C, Navionis AS, Mahamat-Saleh Y, Jaafar RF, Baurecht H, Guevara M, Etxezarreta PA, Verschuren WMM, Boer JMA, Olsen A, Tjønneland A, Simeon V, Castro-Espin C, Aune D, Heath AK, Gunter M, Colorado-Yohar SM, Zilhão NR, Dahm CC, Llanaj E, Schulze MB, Petrova D, Sieri S, Ricceri F, Masala G, Key T, Viallon V, Rinaldi S, Freisling H, Dossus L. Association of body shape phenotypes and body fat distribution indexes with inflammatory biomarkers in the European Prospective Investigation into Cancer and Nutrition (EPIC) and UK Biobank. BMC Med 2024; 22:334. [PMID: 39148045 PMCID: PMC11328449 DOI: 10.1186/s12916-024-03544-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 07/29/2024] [Indexed: 08/17/2024] Open
Abstract
BACKGROUND The allometric body shape index (ABSI) and hip index (HI), as well as multi-trait body shape phenotypes, have not yet been compared in their associations with inflammatory markers. The aim of this study was to examine the relationship between novel and traditional anthropometric indexes with inflammation using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) and UK Biobank cohorts. METHODS Participants from EPIC (n = 17,943, 69.1% women) and UK Biobank (n = 426,223, 53.2% women) with data on anthropometric indexes and C-reactive protein (CRP) were included in this cross-sectional analysis. A subset of women in EPIC also had at least one measurement for interleukins, tumour necrosis factor alpha, interferon gamma, leptin, and adiponectin. Four distinct body shape phenotypes were derived by a principal component (PC) analysis on height, weight, body mass index (BMI), waist (WC) and hip circumferences (HC), and waist-to-hip ratio (WHR). PC1 described overall adiposity, PC2 tall with low WHR, PC3 tall and centrally obese, and PC4 high BMI and weight with low WC and HC, suggesting an athletic phenotype. ABSI, HI, waist-to-height ratio and waist-to-hip index (WHI) were also calculated. Linear regression models were carried out separately in EPIC and UK Biobank stratified by sex and adjusted for age, smoking status, education, and physical activity. Results were additionally combined in a random-effects meta-analysis. RESULTS Traditional anthropometric indexes, particularly BMI, WC, and weight were positively associated with CRP levels, in men and women. Body shape phenotypes also showed distinct associations with CRP. Specifically, PC2 showed inverse associations with CRP in EPIC and UK Biobank in both sexes, similarly to height. PC3 was inversely associated with CRP among women, whereas positive associations were observed among men. CONCLUSIONS Specific indexes of body size and body fat distribution showed differential associations with inflammation in adults. Notably, our results suggest that in women, height may mitigate the impact of a higher WC and HC on inflammation. This suggests that subtypes of adiposity exhibit substantial variation in their inflammatory potential, which may have implications for inflammation-related chronic diseases.
Collapse
Affiliation(s)
- Esther M González-Gil
- Nutrition and Metabolism Branch, International Agency for Research On Cancer, World Health Organization, 69372, Lyon, CEDEX 08, France
| | - Laia Peruchet-Noray
- Nutrition and Metabolism Branch, International Agency for Research On Cancer, World Health Organization, 69372, Lyon, CEDEX 08, France
- Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain
| | - Anja M Sedlmeier
- Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany
- Center for Translational Oncology, University Hospital Regensburg, Regensburg, Germany
- Bavarian Cancer Research Center (BZKF), Regensburg, Germany
| | - Sofia Christakoudi
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Carine Biessy
- Nutrition and Metabolism Branch, International Agency for Research On Cancer, World Health Organization, 69372, Lyon, CEDEX 08, France
| | - Anne-Sophie Navionis
- Nutrition and Metabolism Branch, International Agency for Research On Cancer, World Health Organization, 69372, Lyon, CEDEX 08, France
| | - Yahya Mahamat-Saleh
- Nutrition and Metabolism Branch, International Agency for Research On Cancer, World Health Organization, 69372, Lyon, CEDEX 08, France
| | - Rola F Jaafar
- Nutrition and Metabolism Branch, International Agency for Research On Cancer, World Health Organization, 69372, Lyon, CEDEX 08, France
| | - Hansjörg Baurecht
- Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany
| | - Marcela Guevara
- Instituto de Salud Pública y Laboral de Navarra, 31003, Pamplona, Spain
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029, Madrid, Spain
- Navarra Institute for Health Research (IdiSNA), 31008, Pamplona, Spain
| | - Pilar Amiano Etxezarreta
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029, Madrid, Spain
- Sub Directorate for Public Health and Addictions of Gipuzkoa, Ministry of Health of the Basque Government, San Sebastian, Spain
- Epidemiology of Chronic and Communicable Diseases Group, BioGipuzkoa (BioDonostia) Health Research Institute, San Sebastián, Spain
| | - W M Monique Verschuren
- Centre forPrevention, Lifestyle and Health, National Institute for Public Health and the Environment, PO Box 1, 3720 BA, Bilthoven, the Netherlands
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Jolanda M A Boer
- Centre forPrevention, Lifestyle and Health, National Institute for Public Health and the Environment, PO Box 1, 3720 BA, Bilthoven, the Netherlands
| | - Anja Olsen
- Danish Cancer Institute, Danish Cancer Society, Diet, Cancer and Health Strandboulevarden 49 2100, Copenhagen, Denmark
- Department of Public Health, University of Aarhus, Copenhagen, Denmark
| | - Anne Tjønneland
- Danish Cancer Institute, Danish Cancer Society, Diet, Cancer and Health Strandboulevarden 49 2100, Copenhagen, Denmark
- Department of Public Health, University of Copenhagen, Copenhagen, Denmark
| | - Vittorio Simeon
- Dipartimento Di Salute Mentale E Fisica E Medicina Preventiva, Università Degli Studi Della Campania 'Luigi Vanvitelli', Napoli, Italy
| | - Carlota Castro-Espin
- Unit of Nutrition and Cancer, Catalan Institute of Oncology-ICO, L'Hospitalet de Llobregat, Barcelona, Spain
- Nutrition and Cancer Group, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Dagfinn Aune
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- Department of Research, The Cancer Registry of Norway, Oslo, Norway
- Department of Nutrition, Oslo New University College, Oslo, Norway
| | - Alicia K Heath
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Marc Gunter
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Sandra M Colorado-Yohar
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029, Madrid, Spain
- Department of Epidemiology, Murcia Regional Health Council-IMIB, Murcia, Spain
- Research Group On Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia
| | - Nuno R Zilhão
- Department of Public Health, Aarhus University, Aarhus, Denmark
| | | | - Erand Llanaj
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
- German Center for Diabetes Research (DZD), Munchen-Neuherberg, Germany
| | - Matthias B Schulze
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
- Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany
| | - Dafina Petrova
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029, Madrid, Spain
- Escuela Andaluza de Salud Pública (EASP), 18011, Granada, Spain
- Instituto de Investigación Biosanitaria Ibs, GRANADA, 18012, Granada, Spain
| | - Sabina Sieri
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori Di Milano, Milan, Italy
| | - Fulvio Ricceri
- Centre for Biostatistics, Epidemiology, and Public Health (C-BEPH) Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Giovanna Masala
- Clinical Epidemiology Unit, Institute for Cancer Research, Prevention, and Clinical Network (ISPRO), Florence, Italy
| | - Tim Key
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Vivian Viallon
- Nutrition and Metabolism Branch, International Agency for Research On Cancer, World Health Organization, 69372, Lyon, CEDEX 08, France
| | - Sabina Rinaldi
- Nutrition and Metabolism Branch, International Agency for Research On Cancer, World Health Organization, 69372, Lyon, CEDEX 08, France
| | - Heinz Freisling
- Nutrition and Metabolism Branch, International Agency for Research On Cancer, World Health Organization, 69372, Lyon, CEDEX 08, France
| | - Laure Dossus
- Nutrition and Metabolism Branch, International Agency for Research On Cancer, World Health Organization, 69372, Lyon, CEDEX 08, France
| |
Collapse
|
|
3
|
Baldelli S, Aiello G, Mansilla Di Martino E, Campaci D, Muthanna FMS, Lombardo M. The Role of Adipose Tissue and Nutrition in the Regulation of Adiponectin. Nutrients 2024; 16:2436. [PMID: 39125318 PMCID: PMC11313710 DOI: 10.3390/nu16152436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 07/21/2024] [Accepted: 07/25/2024] [Indexed: 08/12/2024] Open
Abstract
Adipose tissue (AT), composed mainly of adipocytes, plays a critical role in lipid control, metabolism, and energy storage. Once considered metabolically inert, AT is now recognized as a dynamic endocrine organ that regulates food intake, energy homeostasis, insulin sensitivity, thermoregulation, and immune responses. This review examines the multifaceted role of adiponectin, a predominant adipokine released by AT, in glucose and fatty acid metabolism. We explore the regulatory mechanisms of adiponectin, its physiological effects and its potential as a therapeutic target for metabolic diseases such as type 2 diabetes, cardiovascular disease and fatty liver disease. Furthermore, we analyze the impact of various dietary patterns, specific nutrients, and physical activities on adiponectin levels, highlighting strategies to improve metabolic health. Our comprehensive review provides insights into the critical functions of adiponectin and its importance in maintaining systemic metabolic homeostasis.
Collapse
Affiliation(s)
- Sara Baldelli
- Department for the Promotion of Human Science and Quality of Life, San Raffaele Open University, Via di Val Cannuta, 247, 00166 Rome, Italy (E.M.D.M.)
- IRCCS San Raffaele Roma, 00166 Rome, Italy
| | - Gilda Aiello
- Department for the Promotion of Human Science and Quality of Life, San Raffaele Open University, Via di Val Cannuta, 247, 00166 Rome, Italy (E.M.D.M.)
| | - Eliana Mansilla Di Martino
- Department for the Promotion of Human Science and Quality of Life, San Raffaele Open University, Via di Val Cannuta, 247, 00166 Rome, Italy (E.M.D.M.)
| | - Diego Campaci
- Department for the Promotion of Human Science and Quality of Life, San Raffaele Open University, Via di Val Cannuta, 247, 00166 Rome, Italy (E.M.D.M.)
| | - Fares M. S. Muthanna
- Pharmacy Department, Faculty of Medicine and Health Sciences, University of Science and Technology-Aden, Alshaab Street, Enmaa City 22003, Yemen
| | - Mauro Lombardo
- Department for the Promotion of Human Science and Quality of Life, San Raffaele Open University, Via di Val Cannuta, 247, 00166 Rome, Italy (E.M.D.M.)
| |
Collapse
|
|
4
|
Watts EL, Moore SC, Gunter MJ, Chatterjee N. Adiposity and cancer: meta-analysis, mechanisms, and future perspectives. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.02.16.24302944. [PMID: 38405761 PMCID: PMC10889047 DOI: 10.1101/2024.02.16.24302944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/27/2024]
Abstract
Obesity is a recognised risk factor for many cancers and with rising global prevalence, has become a leading cause of cancer. Here we summarise the current evidence from both population-based epidemiologic investigations and experimental studies on the role of obesity in cancer development. This review presents a new meta-analysis using data from 40 million individuals and reports positive associations with 19 cancer types. Utilising major new data from East Asia, the meta-analysis also shows that the strength of obesity and cancer associations varies regionally, with stronger relative risks for several cancers in East Asia. This review also presents current evidence on the mechanisms linking obesity and cancer and identifies promising future research directions. These include the use of new imaging data to circumvent the methodological issues involved with body mass index and the use of omics technologies to resolve biologic mechanisms with greater precision and clarity.
Collapse
Affiliation(s)
- Eleanor L Watts
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Shady Grove, MD, USA
| | - Steven C Moore
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Shady Grove, MD, USA
| | - Marc J Gunter
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Nilanjan Chatterjee
- Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, USA
- Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, USA
| |
Collapse
|
|
5
|
Nimptsch K, Aleksandrova K, Pham TT, Papadimitriou N, Janke J, Christakoudi S, Heath A, Olsen A, Tjønneland A, Schulze MB, Katzke V, Kaaks R, van Guelpen B, Harbs J, Palli D, Macciotta A, Pasanisi F, Yohar SMC, Guevara M, Amiano P, Grioni S, Jakszyn PG, Figueiredo JC, Samadder NJ, Li CI, Moreno V, Potter JD, Schoen RE, Um CY, Weiderpass E, Jenab M, Gunter MJ, Pischon T. Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer. BMC Med 2023; 21:391. [PMID: 37833736 PMCID: PMC10576353 DOI: 10.1186/s12916-023-03104-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 10/04/2023] [Indexed: 10/15/2023] Open
Abstract
BACKGROUND Fatty acid binding protein 4 (FABP-4) is a lipid-binding adipokine upregulated in obesity, which may facilitate fatty acid supply for tumor growth and promote insulin resistance and inflammation and may thus play a role in colorectal cancer (CRC) development. We aimed to investigate the association between circulating FABP-4 and CRC and to assess potential causality using a Mendelian randomization (MR) approach. METHODS The association between pre-diagnostic plasma measurements of FABP-4 and CRC risk was investigated in a nested case-control study in 1324 CRC cases and the same number of matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A two-sample Mendelian randomization study was conducted based on three genetic variants (1 cis, 2 trans) associated with circulating FABP-4 identified in a published genome-wide association study (discovery n = 20,436) and data from 58,131 CRC cases and 67,347 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. RESULTS In conditional logistic regression models adjusted for potential confounders including body size, the estimated relative risk, RR (95% confidence interval, CI) per one standard deviation, SD (8.9 ng/mL) higher FABP-4 concentration was 1.01 (0.92, 1.12) overall, 0.95 (0.80, 1.13) in men and 1.09 (0.95, 1.25) in women. Genetically determined higher FABP-4 was not associated with colorectal cancer risk (RR per FABP-4 SD was 1.10 (0.95, 1.27) overall, 1.03 (0.84, 1.26) in men and 1.21 (0.98, 1.48) in women). However, in a cis-MR approach, a statistically significant association was observed in women (RR 1.56, 1.09, 2.23) but not overall (RR 1.23, 0.97, 1.57) or in men (0.99, 0.71, 1.37). CONCLUSIONS Taken together, these analyses provide no support for a causal role of circulating FABP-4 in the development of CRC, although the cis-MR provides some evidence for a positive association in women, which may deserve to be investigated further.
Collapse
Affiliation(s)
- Katharina Nimptsch
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany.
| | - Krasimira Aleksandrova
- Department Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology, Bremen, Germany
- Faculty of Human and Health Sciences, University of Bremen, Bremen, Germany
| | - Thu Thi Pham
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany
- Charité - Universitaetsmedizin Berlin, Corporate Member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, Berlin, Germany
| | - Nikos Papadimitriou
- Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Jürgen Janke
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany
- Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Biobank Technology Platform, Berlin, Germany
| | - Sofia Christakoudi
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- Department of Inflammation Biology, School of Immunology and Microbial Sciences, King's College London, London, UK
| | - Alicia Heath
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Anja Olsen
- Danish Cancer Society Research Center, Copenhagen, Denmark
- Department of Public Health, University of Århus, Århus, Denmark
| | - Anne Tjønneland
- Danish Cancer Society Research Center, Copenhagen, Denmark
- Department of Public Health, University of Copenhagen, Copenhagen, Denmark
| | - Matthias B Schulze
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nutehtal, Germany
- Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany
| | - Verena Katzke
- Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Rudolf Kaaks
- Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Bethany van Guelpen
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
- Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden
| | - Justin Harbs
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
| | - Domenico Palli
- Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy
| | - Alessandra Macciotta
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Fabrizio Pasanisi
- Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
| | - Sandra Milena Colorado Yohar
- Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain
- CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia
| | - Marcela Guevara
- CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Instituto de Salud Pública de Navarra, Pamplona, 31003, Spain
- Navarra Institute for Health Research (IdiSNA), Pamplona, 31008, Spain
| | - Pilar Amiano
- CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Ministry of Health of the Basque Government, Sub Directorate for Public Health and Addictions of Gipuzkoa, San Sebastian, Spain
- Epidemiology of Chronic and Communicable Diseases Group, Biodonostia Health Research Institute, San Sebastián, Spain
| | - Sara Grioni
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, 20133, Italy
| | - Paula Gabriela Jakszyn
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain
- Blanquerna School of Health Sciences, Ramon Llull University, Barcelona, Spain
| | - Jane C Figueiredo
- Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USA
| | - N Jewel Samadder
- Division of Gastroenterology and Hepatology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Phoenix, AZ, USA
| | - Christopher I Li
- Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Victor Moreno
- CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Oncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
- Department of Clinical Sciences, Faculty of Medicine and Health Sciences and Universitat de Barcelona Institute of Complex Systems (UBICS), University of Barcelona (UB), L'Hospitalet de Llobregat, Barcelona, Spain
| | - John D Potter
- Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Research Centre for Hauora and Health, Massey University, Wellington, New Zealand
| | - Robert E Schoen
- Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Caroline Y Um
- Department of Population Science, American Cancer Society, Atlanta, GA, USA
| | - Elisabete Weiderpass
- International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Mazda Jenab
- Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Marc J Gunter
- Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Tobias Pischon
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany
- Charité - Universitaetsmedizin Berlin, Corporate Member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, Berlin, Germany
- Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Biobank Technology Platform, Berlin, Germany
| |
Collapse
|
|
6
|
Lécuyer L, Laouali N, Viallon V, Artaud F, Hébert JR, Shivappa N, Agudo A, Tjønneland A, Mellemkjær L, Kaaks R, Katzke VA, Schulze MB, Frenoy P, Mancini FR, De Magistris MS, Macciotta A, Masala G, Agnoli C, Tumino R, Boer JMA, Verschuren WMM, Enget Jensen TM, Olsen KS, Skeie G, Chirlaque MD, Petrova D, Castro-Espin C, Quirós JR, Guevara M, Amiano P, Borné Y, Sandström M, Nilsson LM, Heath AK, Mayen AL, Huybrechts I, Weiderpass E, Boutron-Ruault MC, Dossus L, Rinaldi S, Truong T. Associations between dietary inflammatory scores and biomarkers of inflammation in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Clin Nutr 2023; 42:1115-1125. [PMID: 37271707 DOI: 10.1016/j.clnu.2023.05.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 04/14/2023] [Accepted: 05/12/2023] [Indexed: 06/06/2023]
Abstract
BACKGROUND Since the first version of the dietary inflammatory index (DII®) developed in the past decade, several other versions have been developed. However, to date no study has attempted to compare these versions with respect to their associations with biomarkers of inflammation. OBJECTIVE We aimed to investigate the relationship between four dietary inflammatory scores [DII, two energy-adjusted derivatives (E-DII and E-DIIr), and the Inflammatory Score of the Diet (ISD)], and circulating levels of several inflammatory markers and adipokines. METHODS This study included 17 637 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with at least one marker of inflammation measured in blood. Associations between the four scores and C-reactive protein (CRP), interleukin (IL)6, IL10, IL1RA, tumor necrosis factor-α (TNFα), soluble tumor necrosis factor receptor-1 (sTNFR1), sTNFR2, leptin, soluble leptin receptor (sLeptin R), adiponectin, and High Molecular Weight (HMW) adiponectin were evaluated using multivariable linear regressions adjusted for potential confounders. RESULTS Positive associations were observed between the four dietary inflammatory scores and levels of CRP, IL6, sTNFR1, sTNFR2 and leptin. However, only the DII and the ISD were positively associated with IL1RA levels and only the DII and the E-DIIr were positively associated with TNFα levels. The proportion of variance of each biomarker explained by the scores was lower than 2%, which was equivalent to the variance explained by smoking status but much lower than that explained by body mass index. CONCLUSIONS Our results suggest that the four dietary inflammatory scores were associated with some biomarkers of inflammation and could be used to assess the inflammatory potential of diet in European adults but are not sufficient to capture the inflammatory status of an individual. These findings can help to better understand the inflammatory potential of diet, but they need to be replicated in studies with repeated dietary measurements.
Collapse
Affiliation(s)
- Lucie Lécuyer
- Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team "Exposome and Heredity", 94807, Villejuif, France
| | - Nasser Laouali
- Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team "Exposome and Heredity", 94807, Villejuif, France; Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA
| | - Vivian Viallon
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Fanny Artaud
- Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team "Exposome and Heredity", 94807, Villejuif, France
| | - James R Hébert
- Cancer Prevention and Control Program and Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC, USA; Department of Nutrition, Connecting Health Innovations LLC, Columbia, SC, USA
| | - Nitin Shivappa
- Cancer Prevention and Control Program and Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC, USA; Department of Nutrition, Connecting Health Innovations LLC, Columbia, SC, USA
| | - Antonio Agudo
- Unit of Nutrition and Cancer, Catalan Institute of Oncology - ICO, L'Hospitalet de Llobregat, Spain; Nutrition and Cancer Group, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute - IDIBELL, L'Hospitalet de Llobregat, Spain
| | - Anne Tjønneland
- Danish Cancer Society Research Center, "Diet, Cancer and Health", Copenhagen, Denmark; University of Copenhagen, Department of Public Health, Copenhagen, Denmark
| | - Lene Mellemkjær
- Danish Cancer Society Research Center, "Diet, Cancer and Health", Copenhagen, Denmark
| | - Rudolf Kaaks
- Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Verena A Katzke
- Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Matthias B Schulze
- German Institute of Human Nutrition Potsdam-Rehbruecke, Dept. of Molecular Epidemiology, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany
| | - Pauline Frenoy
- Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team "Exposome and Heredity", 94807, Villejuif, France
| | - Francesca Romana Mancini
- Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team "Exposome and Heredity", 94807, Villejuif, France
| | | | - Alessandra Macciotta
- Centre for Biostatistics, Epidemiology, and Public Health (C-BEPH), Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Giovanna Masala
- Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy
| | - Claudia Agnoli
- Epidemiology and Prevention Unit, Department of Epidemiology and Data Science, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Rosario Tumino
- Hyblean Association for Epidemiological Research, AIRE-ONLUS, Ragusa, Italy
| | - Jolanda M A Boer
- National Institute for Public Health and the Environment, Bilthoven, the Netherlands
| | - W M Monique Verschuren
- National Institute for Public Health and the Environment, Bilthoven, the Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, University Utrecht, Utrecht, the Netherlands
| | - Torill M Enget Jensen
- Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway
| | - Karina Standahl Olsen
- Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway
| | - Guri Skeie
- Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway
| | - María-Dolores Chirlaque
- Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain; CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain
| | - Dafina Petrova
- CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Escuela Andaluza de Salud Pública (EASP), 18011, Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, 18012, Granada, Spain
| | - Carlota Castro-Espin
- Unit of Nutrition and Cancer, Catalan Institute of Oncology - ICO, L'Hospitalet de Llobregat, Spain; Nutrition and Cancer Group, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute - IDIBELL, L'Hospitalet de Llobregat, Spain
| | | | - Marcela Guevara
- CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Navarra Public Health Institute, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
| | - Pilar Amiano
- CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Ministry of Health of the Basque Government, Sub Directorate for Public Health and Addictions of Gipuzkoa, San Sebastián, Spain; Biodonostia Health Research Institute, Epidemiology of Chronic and Communicable Diseases Group, San Sebastián, Spain
| | - Yan Borné
- Nutritional Epidemiology, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Malmö, Sweden
| | - Maria Sandström
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
| | - Lena Maria Nilsson
- Department of Epidemiology and Global Health/ Arcum, Arctic Centre, Umeå University, Umeå, Sweden
| | - Alicia K Heath
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Ana-Lucia Mayen
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Inge Huybrechts
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Elisabete Weiderpass
- International Agency for Research on Cancer, World Health Organization, Lyon, France
| | | | - Laure Dossus
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Sabina Rinaldi
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Thérèse Truong
- Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team "Exposome and Heredity", 94807, Villejuif, France.
| |
Collapse
|
|
7
|
Pham TT, Nimptsch K, Aleksandrova K, Jenab M, Reichmann R, Wu K, Tjønneland A, Kyrø C, Schulze MB, Kaaks R, Katzke V, Palli D, Pasanisi F, Ricceri F, Tumino R, Krogh V, Roodhart J, Castilla J, Sánchez MJ, Colorado-Yohar SM, Harbs J, Rutegård M, Papier K, Aglago EK, Dimou N, Mayen-Chacon AL, Weiderpass E, Pischon T. Pre-Diagnostic Circulating Resistin Concentrations Are Not Associated with Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition Study. Cancers (Basel) 2022; 14:5499. [PMID: 36428592 PMCID: PMC9688251 DOI: 10.3390/cancers14225499] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 10/31/2022] [Accepted: 11/01/2022] [Indexed: 11/12/2022] Open
Abstract
Resistin is a polypeptide implicated in inflammatory processes, and as such could be linked to colorectal carcinogenesis. In case-control studies, higher resistin levels have been found in colorectal cancer (CRC) patients compared to healthy individuals. However, evidence for the association between pre-diagnostic resistin and CRC risk is scarce. We investigated pre-diagnostic resistin concentrations and CRC risk within the European Prospective Investigation into Cancer and Nutrition using a nested case-control study among 1293 incident CRC-diagnosed cases and 1293 incidence density-matched controls. Conditional logistic regression models controlled for matching factors (age, sex, study center, fasting status, and women-related factors in women) and potential confounders (education, dietary and lifestyle factors, body mass index (BMI), BMI-adjusted waist circumference residuals) were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for CRC. Higher circulating resistin concentrations were not associated with CRC (RR per doubling resistin, 1.11; 95% CI 0.94-1.30; p = 0.22). There were also no associations with CRC subgroups defined by tumor subsite or sex. However, resistin was marginally associated with a higher CRC risk among participants followed-up maximally two years, but not among those followed-up after more than two years. We observed no substantial correlation between baseline circulating resistin concentrations and adiposity measures (BMI, waist circumference), adipokines (adiponectin, leptin), or metabolic and inflammatory biomarkers (C-reactive protein, C-peptide, high-density lipoprotein cholesterol, reactive oxygen metabolites) among controls. In this large-scale prospective cohort, there was little evidence of an association between baseline circulating resistin concentrations and CRC risk in European men and women.
Collapse
Affiliation(s)
- Thu-Thi Pham
- Molecular Epidemiology Research Group, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany
| | - Katharina Nimptsch
- Molecular Epidemiology Research Group, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany
| | - Krasimira Aleksandrova
- Department of Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology—BIPS, 28359 Bremen, Germany
- Faculty of Human and Health Sciences, University of Bremen, 28359 Bremen, Germany
| | - Mazda Jenab
- Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), World Health Organization, 150 Cours Albert Thomas, CEDEX 08, 69372 Lyon, France
| | - Robin Reichmann
- Department of Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology—BIPS, 28359 Bremen, Germany
| | - Kana Wu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
| | - Anne Tjønneland
- Danish Cancer Society Research Center, 2100 Copenhagen, Denmark
- Department of Public Health, University of Copenhagen, DK-1353 Copenhagen, Denmark
| | - Cecilie Kyrø
- Danish Cancer Society Research Center, 2100 Copenhagen, Denmark
| | - Matthias B. Schulze
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany
- Institute of Nutritional Science, University of Potsdam, 14558 Nuthetal, Germany
| | - Rudolf Kaaks
- Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Verena Katzke
- Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Domenico Palli
- Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), 50139 Florence, Italy
| | - Fabrizio Pasanisi
- Dipartimento di Medicina Clinica E Chirurgia, Federico Ii University, 80131 Naples, Italy
| | - Fulvio Ricceri
- Centre for Biostatistics, Epidemiology, and Public Health (C-BEPH), Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy
- Unit of Epidemiology, Regional Health Service ASL TO3, 10095 Grugliasco, Italy
| | - Rosario Tumino
- Hyblean Association for Epidemiological Research, AIRE ONLUS, 97100 Ragusa, Italy
| | - Vittorio Krogh
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Via Venezian 1, 20133 Milan, Italy
| | - Jeanine Roodhart
- Department of Medical Oncology, UMC Utrecht, 3584 CX Utrecht, The Netherlands
| | - Jesús Castilla
- Navarra Public Health Institute—IdiSNA, 31003 Pamplona, Spain
- CIBER Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain
| | - Maria-Jose Sánchez
- CIBER Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain
- Escuela Andaluza de Salud Pública (EASP), 18011 Granada, Spain
- Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain
- Department of Preventive Medicine and Public Health, University of Granada, 18071 Granada, Spain
| | - Sandra Milena Colorado-Yohar
- CIBER Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain
- Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, 30008 Murcia, Spain
- Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín 050010, Colombia
| | - Justin Harbs
- Department of Radiation Sciences, Oncology, Umeå University, SE-901 87 Umeå, Sweden
| | - Martin Rutegård
- Department of Surgical and Perioperative Sciences, Surgery, Umeå University, SE-901 87 Umeå, Sweden
- Wallenberg Centre for Molecular Medicine, Umeå University, SE-901 87 Umeå, Sweden
| | - Keren Papier
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK
| | - Elom K. Aglago
- Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK
| | - Niki Dimou
- Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), World Health Organization, 150 Cours Albert Thomas, CEDEX 08, 69372 Lyon, France
| | - Ana-Lucia Mayen-Chacon
- Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), World Health Organization, 150 Cours Albert Thomas, CEDEX 08, 69372 Lyon, France
| | - Elisabete Weiderpass
- International Agency for Research on Cancer, World Health Organization, 69372 Lyon, France
| | - Tobias Pischon
- Molecular Epidemiology Research Group, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany
- Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Biobank Technology Platform, 13125 Berlin, Germany
- Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Core Facility Biobank, 13125 Berlin, Germany
| |
Collapse
|
|
8
|
Wang Y, Li J, Fu X, Li J, Liu L, Alkohlani A, Tan SC, Low TY, Hou Y. Association of circulating leptin and adiponectin levels with colorectal cancer risk: A systematic review and meta-analysis of case-control studies. Cancer Epidemiol 2021; 73:101958. [PMID: 34020315 DOI: 10.1016/j.canep.2021.101958] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 05/02/2021] [Accepted: 05/05/2021] [Indexed: 02/06/2023]
Abstract
PURPOSE Leptin and adiponectin are adipokines which have been commonly implicated in carcinogenesis. As such, many studies have investigated the association of circulating leptin and adiponectin levels with colorectal cancer (CRC) risk. However, the results remained inconsistent. METHODS In this work, we performed a systematic review and meta-analysis to precisely examine the association between circulating levels of leptin and adiponectin and CRC risk. A systematic literature search was performed in PubMed/MEDLINE, Scopus, Web of Science, and EMBASE databases from inception until October 2020. The pooled effect size was then estimated by calculating the odds ratio (OR). RESULTS A total of 23 records (comprising 26 studies) were included in the meta-analysis. The overall analysis found that circulating levels of leptin and adiponectin were not significantly associated with CRC risk (P > 0.05). Interestingly, subgroup analysis revealed that a higher level of adiponectin was significantly associated with an increased CRC risk among overweight individuals (OR = 1.16; 95 % CI: 1.02, 1.32), and a decreased CRC risk among normal weight individuals (OR = 0.76; 95 % CI: 0.62, 0.92). Besides, a higher level of adiponectin was also significantly associated with a decreased risk of CRC in men (OR = 0.76; 95 % CI: 0.59, 0.98). CONCLUSIONS In conclusion, circulating leptin level was not associated with CRC risk, but that of adiponectin was associated with CRC risk only in specific subgroups.
Collapse
Affiliation(s)
- Yan Wang
- Department of Oncology and Hematology, The First People's Hospital of Longquanyi District, Chengdu, Chengdu, Sichuan, 510100, China
| | - Junyong Li
- Department of Oncology and Hematology, The First People's Hospital of Longquanyi District, Chengdu, Chengdu, Sichuan, 510100, China
| | - Xiaolin Fu
- Department of Oncology and Hematology, The First People's Hospital of Longquanyi District, Chengdu, Chengdu, Sichuan, 510100, China
| | - Jialing Li
- Department of Oncology and Hematology, The First People's Hospital of Longquanyi District, Chengdu, Chengdu, Sichuan, 510100, China
| | - Lihua Liu
- Department of Oncology and Hematology, The First People's Hospital of Longquanyi District, Chengdu, Chengdu, Sichuan, 510100, China
| | | | - Shing Cheng Tan
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Teck Yew Low
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Yue Hou
- Department of Oncology and Hematology, The First People's Hospital of Longquanyi District, Chengdu, Chengdu, Sichuan, 510100, China.
| |
Collapse
|
|
9
|
Association between pre-diagnostic circulating adipokines and colorectal cancer and adenoma in the CLUE II cohort. Cancer Causes Control 2021; 32:871-881. [PMID: 33999316 DOI: 10.1007/s10552-021-01441-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Accepted: 05/01/2021] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Obesity is a known risk factor for colorectal cancer (CRC) and adenoma. Obese individuals have higher circulating concentrations of certain endocrine and immune factors produced by adipocytes thought to partially underlie the association between obesity and colorectal neoplasia. Thus, we evaluated the association of plasma concentrations of adiponectin, leptin, and soluble tumor necrosis factor receptor-2 (sTNFR2) with CRC and adenoma. METHODS We ascertained 193 CRC cases and 193 matched controls, and 131 colorectal adenoma cases and 131 matched controls who had had an endoscopy nested in the CLUE II cohort of Washington County, MD. Plasma markers were measured using ELISA. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from conditional logistic regression for quartiles of the plasma markers separately for CRC and adenoma. RESULTS Adjusting for leptin and adiponectin, sTNFR2 was positively associated with CRC only in men (Q4 vs. Q1: OR = 3.14, 95% CI 1.11-8.86), which was unchanged adjusting for BMI (3.46, 95% CI 1.19-10.06). Leptin and adiponectin were not associated with CRC risk overall or in men or women. Adiponectin, leptin, and sTNFR2 were not associated with adenoma risk overall or in men or women. CONCLUSION In this study, leptin and adiponectin were not associated with colorectal carcinogenesis and thus do not appear to underlie the association between obesity and colorectal carcinogenesis. sTNFR2, which we measured as a correlate of TNF-α, was positively associated with CRC in men adjusting for BMI, suggesting that TNF-α may influence colorectal carcinogenesis independent of adipocyte production.
Collapse
|
|
10
|
Dimou NL, Papadimitriou N, Mariosa D, Johansson M, Brennan P, Peters U, Chanock SJ, Purdue M, Bishop DT, Gago‐Dominquez M, Giles GG, Moreno V, Platz EA, Tangen CM, Wolk A, Zheng W, Wu X, Campbell PT, Giovannucci E, Lin Y, Gunter MJ, Murphy N. Circulating adipokine concentrations and risk of five obesity-related cancers: A Mendelian randomization study. Int J Cancer 2021; 148:1625-1636. [PMID: 33038280 PMCID: PMC7894468 DOI: 10.1002/ijc.33338] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 08/27/2020] [Accepted: 09/17/2020] [Indexed: 12/20/2022]
Abstract
Obesity is considered a chronic inflammatory state characterized by continued secretion of adipokines and cytokines. Experimental and epidemiological evidence indicates that circulating adipokines may be associated with the development of obesity-related cancers, but it is unclear if these associations are causal or confounded. We examined potential causal associations of specific adipokines (adiponectin, leptin, soluble leptin receptor [sOB-R] and plasminogen activator inhibitor-1 [PAI-1]) with five obesity-related cancers (colorectal, pancreatic, renal cell carcinoma [RCC], ovarian and endometrial) using Mendelian randomization (MR) methods. We used summary-level data from large genetic consortia for 114 530 cancer cases and 245 284 controls. We constructed genetic instruments using 18 genetic variants for adiponectin, 2 for leptin and 4 for both sOB-R and PAI-1 (P value for inclusion<5 × 10-8 ). Causal estimates were obtained using two-sample MR methods. In the inverse-variance weighted models, we found an inverse association between adiponectin and risk of colorectal cancer (odds ratio per 1 μg/mL increment in adiponectin concentration: 0.90 [95% confidence interval = 0.84-0.97]; P = .01); but, evidence of horizontal pleiotropy was detected and the association was not present when this was taken into consideration. No association was found for adiponectin and risks of pancreatic cancer, RCC, ovarian cancer and endometrial cancer. Leptin, sOB-R and PAI-1 were also similarly unrelated to risk of obesity-related cancers. Despite the large sample size, our MR analyses do not support causal effects of circulating adiponectin, leptin, sOB-R and PAI-1 concentrations on the development of five obesity-related cancers.
Collapse
Affiliation(s)
- Niki L. Dimou
- Section of Nutrition and Metabolism, International Agency for Research on CancerLyonFrance
| | - Nikos Papadimitriou
- Section of Nutrition and Metabolism, International Agency for Research on CancerLyonFrance
| | - Daniela Mariosa
- Section of Genetics, International Agency for Research on CancerLyonFrance
| | - Mattias Johansson
- Section of Genetics, International Agency for Research on CancerLyonFrance
| | - Paul Brennan
- Section of Genetics, International Agency for Research on CancerLyonFrance
| | - Ulrike Peters
- Fred Hutchinson Cancer Research CenterSeattleWashingtonUSA
| | - Stephen J. Chanock
- Division of Cancer Epidemiology and Genetics, National Cancer InstituteNational Institutes of HealthBethesdaMarylandUSA
| | - Mark Purdue
- Division of Cancer Epidemiology and Genetics, National Cancer InstituteNational Institutes of HealthBethesdaMarylandUSA
| | | | - Manuela Gago‐Dominquez
- Fundación Gallega de Medicina Genómica, Grupo de Genéticadel CáncerInstituto de Investigación Sanitaria de Santiago IDISComplejo Hospitalario Univ. Santiago‐CHUS, SERGAS, Santiago de CompostelaSpain
- Moores Cancer CenterUniversity of California San DiegoLa JollaCaliforniaUSA
| | - Graham G. Giles
- Cancer Epidemiology DivisionCancer Council VictoriaMelbourneVictoriaAustralia
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global HealthThe University of MelbourneMelbourneVictoriaAustralia
- Precision MedicineSchool of Clinical Sciences at Monash Health, Monash UniversityClaytonVictoriaAustralia
| | - Victor Moreno
- Oncology Data Analytics ProgramCatalan Institute of Oncology‐IDIBELL, L'Hospitalet de LlobregatBarcelonaSpain
- CIBER Epidemiología y SaludPública (CIBERESP)MadridSpain
- Department of Clinical Sciences, Faculty of MedicineUniversity of BarcelonaBarcelonaSpain
- ONCOBEL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de LlobregatBarcelonaSpain
| | - Elizabeth A. Platz
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public HealthBaltimoreMarylandUSA
| | - Catherine M. Tangen
- SWOG Statistical Center, Fred Hutchinson Cancer Research CenterSeattleWashingtonUSA
| | - Alicja Wolk
- Institute of Environmental Medicine, Karolinska InstitutetStockholmSweden
- Department of Surgical SciencesUppsala UniversityUppsalaSweden
| | - Wei Zheng
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt‐Ingram Cancer CenterVanderbilt UniversityNashvilleTennesseeUSA
| | - Xifeng Wu
- Department of EpidemiologyThe University of Texas MD Anderson Cancer CenterHoustonTexasUSA
- Department of Precision Health and Data Science, School of Public Health and the Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Peter T. Campbell
- Behavioral and Epidemiology Research Group, American Cancer SocietyAtlantaGeorgiaUSA
| | - Edward Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public HealthHarvard UniversityBostonMassachusettsUSA
- Department of NutritionT.H. Chan School of Public HealthBostonMassachusettsUSA
- Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical SchoolBostonMassachusettsUSA
| | - Yi Lin
- Public Health Sciences Division, Fred Hutchinson Cancer Research CenterSeattleWashingtonUSA
| | | | - Marc J. Gunter
- Section of Nutrition and Metabolism, International Agency for Research on CancerLyonFrance
| | - Neil Murphy
- Section of Nutrition and Metabolism, International Agency for Research on CancerLyonFrance
| |
Collapse
|
|
11
|
Chang ML, Yang Z, Yang SS. Roles of Adipokines in Digestive Diseases: Markers of Inflammation, Metabolic Alteration and Disease Progression. Int J Mol Sci 2020; 21:E8308. [PMID: 33167521 PMCID: PMC7663948 DOI: 10.3390/ijms21218308] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 10/30/2020] [Accepted: 11/01/2020] [Indexed: 12/13/2022] Open
Abstract
Adipose tissue is a highly dynamic endocrine tissue and constitutes a central node in the interorgan crosstalk network through adipokines, which cause pleiotropic effects, including the modulation of angiogenesis, metabolism, and inflammation. Specifically, digestive cancers grow anatomically near adipose tissue. During their interaction with cancer cells, adipocytes are reprogrammed into cancer-associated adipocytes and secrete adipokines to affect tumor cells. Moreover, the liver is the central metabolic hub. Adipose tissue and the liver cooperatively regulate whole-body energy homeostasis via adipokines. Obesity, the excessive accumulation of adipose tissue due to hyperplasia and hypertrophy, is currently considered a global epidemic and is related to low-grade systemic inflammation characterized by altered adipokine regulation. Obesity-related digestive diseases, including gastroesophageal reflux disease, Barrett's esophagus, esophageal cancer, colon polyps and cancer, non-alcoholic fatty liver disease, viral hepatitis-related diseases, cholelithiasis, gallbladder cancer, cholangiocarcinoma, pancreatic cancer, and diabetes, might cause specific alterations in adipokine profiles. These patterns and associated bases potentially contribute to the identification of prognostic biomarkers and therapeutic approaches for the associated digestive diseases. This review highlights important findings about altered adipokine profiles relevant to digestive diseases, including hepatic, pancreatic, gastrointestinal, and biliary tract diseases, with a perspective on clinical implications and mechanistic explorations.
Collapse
Affiliation(s)
- Ming-Ling Chang
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
| | - Zinger Yang
- Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA;
| | - Sien-Sing Yang
- Liver Center, Cathay General Hospital Medical Center, Taipei 10630, Taiwan;
| |
Collapse
|
|
12
|
Lee CH, Lui DTW, Cheung CYY, Fong CHY, Yuen MMA, Chow WS, Woo YC, Xu A, Lam KSL. Higher Circulating Adiponectin Concentrations Predict Incident Cancer in Type 2 Diabetes - The Adiponectin Paradox. J Clin Endocrinol Metab 2020; 105:5740218. [PMID: 32072163 DOI: 10.1210/clinem/dgaa075] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Accepted: 02/18/2020] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Despite the beneficial cardiometabolic effects of adiponectin demonstrated in preclinical studies, paradoxically higher circulating adiponectin concentrations have been found in epidemiological studies to be associated with incident cardiovascular events, renal outcomes, and mortality in patients with diabetes. On the other hand, diabetes is also associated with an increased risk of cancer. Here, we investigated prospectively the association between circulating adiponectin concentrations and incident cancer using a cohort of exclusively individuals with type 2 diabetes. MATERIALS AND METHODS Baseline serum adiponectin concentrations were measured in 5658 participants recruited from the Hong Kong West Diabetes Registry. The associations of circulating adiponectin concentrations with incident cancer and cancer-related deaths were evaluated using multivariable Cox regression analysis, with hazard ratio (HR) for adiponectin referring to the respective risk per doubling of serum adiponectin concentration. RESULTS Over a median-follow up of 6.5 years, 7.53% and 3% of participants developed cancer and had cancer-related deaths, respectively. Serum adiponectin concentrations were significantly higher in those who had incident cancer (9.8 μg/mL vs 9.1 μg/mL, P < 0.001) and cancer-related deaths (11.5 μg/mL vs 9.3 μg/mL, P < 0.001) compared with those without. Moreover, in multivariable analyses, serum adiponectin concentration was independently associated with both incident cancer (hazard ratio, 1.19; 95% confidence interval, 1.05-1.35; P = 0.006) and cancer-related deaths (hazard ratio, 1.23; 95% confidence interval, 1.03-1.47; P = 0.024). CONCLUSIONS Higher serum adiponectin concentration was independently associated with incident cancer and cancer-related deaths in type 2 diabetes, indicating that adiponectin paradox can be observed in another major diabetic complication in addition to cardiovascular and kidney diseases.
Collapse
Affiliation(s)
- Chi Ho Lee
- Department of Medicine, University of Hong Kong, Hong Kong SAR
- Research Center of Heart, Brain, Hormone and Healthy Aging, University of Hong Kong, Hong Kong SAR
- State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong SAR
| | - David T W Lui
- Department of Medicine, University of Hong Kong, Hong Kong SAR
| | | | - Carol H Y Fong
- Department of Medicine, University of Hong Kong, Hong Kong SAR
| | | | - Wing Sun Chow
- Department of Medicine, University of Hong Kong, Hong Kong SAR
| | - Yu Cho Woo
- Department of Medicine, University of Hong Kong, Hong Kong SAR
| | - Aimin Xu
- Department of Medicine, University of Hong Kong, Hong Kong SAR
- Research Center of Heart, Brain, Hormone and Healthy Aging, University of Hong Kong, Hong Kong SAR
- State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong SAR
| | - Karen S L Lam
- Department of Medicine, University of Hong Kong, Hong Kong SAR
- Research Center of Heart, Brain, Hormone and Healthy Aging, University of Hong Kong, Hong Kong SAR
- State Key Laboratory of Pharmaceutical Biotechnology, University of Hong Kong, Hong Kong SAR
| |
Collapse
|
|
13
|
A longitudinal study of prediagnostic metabolic biomarkers and the risk of molecular subtypes of colorectal cancer. Sci Rep 2020; 10:5336. [PMID: 32210264 PMCID: PMC7093429 DOI: 10.1038/s41598-020-62129-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2019] [Accepted: 03/02/2020] [Indexed: 01/06/2023] Open
Abstract
Body fatness increases the risk of colorectal cancer (CRC). Insulin resistance and altered adipokines are potential mechanisms, but previous biomarker studies have been inconsistent. Intertumoral heterogeneity might provide an explanation. We investigated insulin, C-peptide, adiponectin, and leptin in relation to CRC molecular subtypes using a nested case-control design (1010 cases, 1010 matched controls, median 12.3 years from baseline to CRC diagnosis) from the population-based Northern Sweden Health and Disease Study. Repeated samples were available from 518 participants. Risks of CRC and subtypes, defined by tumor BRAF and KRAS mutations and microsatellite instability (MSI) status, were estimated using conditional logistic regression and linear mixed models. Higher C-peptide and lower adiponectin were associated with increased CRC risk (odds ratios per standard deviation increase (95% CI): 1.11 (1.01, 1.23) and 0.91 (0.83, 1.00), respectively), though weakened when adjusted for body mass index. Insulin and leptin were not associated with CRC risk. Within-individual time trajectories were similar in cases and controls, and no subtype-specific relationships were identified (all Pheterogeneity > 0.1). Adiponectin was weakly inversely associated with the risk of KRAS-mutated (P = 0.08) but not BRAF-mutated or KRAS/BRAF-wildtype CRC, consistent with the one previous study. These findings contribute to an increased understanding of the complex role of body size in CRC.
Collapse
|
|
14
|
Konigorski S, Yilmaz YE, Janke J, Bergmann MM, Boeing H, Pischon T. Powerful rare variant association testing in a copula-based joint analysis of multiple phenotypes. Genet Epidemiol 2019; 44:26-40. [PMID: 31732979 DOI: 10.1002/gepi.22265] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 08/13/2019] [Accepted: 09/16/2019] [Indexed: 12/16/2022]
Abstract
In genetic association studies of rare variants, the low power of association tests is one of the main challenges. In this study, we propose a new single-marker association test called C-JAMP (Copula-based Joint Analysis of Multiple Phenotypes), which is based on a joint model of multiple phenotypes given genetic markers and other covariates. We evaluated its performance and compared its empirical type I error and power with existing univariate and multivariate single-marker and multi-marker rare-variant tests in extensive simulation studies. C-JAMP yielded unbiased genetic effect estimates and valid type I errors with an adjusted test statistic. When strongly dependent traits were jointly analyzed, C-JAMP had the highest power in all scenarios except when a high percentage of variants were causal with moderate/small effect sizes. When traits with weak or moderate dependence were analyzed, whether C-JAMP or competing approaches had higher power depended on the effect size. When C-JAMP was applied with a misspecified copula function, it still achieved high power in some of the scenarios considered. In a real-data application, we analyzed sequencing data using C-JAMP and performed the first genome-wide association studies of high-molecular-weight and medium-molecular-weight adiponectin plasma concentrations. C-JAMP identified 20 rare variants with p-values smaller than 10-5 , while all other tests resulted in the identification of fewer variants with higher p-values. In summary, the results indicate that C-JAMP is a powerful, flexible, and robust method for association studies, and we identified novel candidate markers for adiponectin. C-JAMP is implemented as an R package and freely available from https://cran.r-project.org/package=CJAMP.
Collapse
Affiliation(s)
- Stefan Konigorski
- Molecular Epidemiology Research Group, Max Delbrück Center (MDC) for Molecular Medicine in the Helmholtz Association, Berlin, Germany.,Digital Health and Machine Learning Research Group, Hasso Plattner Institute for Digital Engineering, Potsdam, Germany
| | - Yildiz E Yilmaz
- Department of Mathematics and Statistics, Memorial University of Newfoundland, St. John's, NL, Canada.,Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.,Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada
| | - Jürgen Janke
- Molecular Epidemiology Research Group, Max Delbrück Center (MDC) for Molecular Medicine in the Helmholtz Association, Berlin, Germany
| | - Manuela M Bergmann
- Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Nuthetal, Germany
| | - Heiner Boeing
- Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Nuthetal, Germany
| | - Tobias Pischon
- Molecular Epidemiology Research Group, Max Delbrück Center (MDC) for Molecular Medicine in the Helmholtz Association, Berlin, Germany.,Charité-Universitätsmedizin Berlin, Berlin, Germany.,DZHK (German Center for Cardiovascular Research), partner site Berlin, Berlin, Germany
| |
Collapse
|
|
15
|
Maeda N, Funahashi T, Matsuzawa Y, Shimomura I. Adiponectin, a unique adipocyte-derived factor beyond hormones. Atherosclerosis 2019; 292:1-9. [PMID: 31731079 DOI: 10.1016/j.atherosclerosis.2019.10.021] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Revised: 10/01/2019] [Accepted: 10/31/2019] [Indexed: 12/11/2022]
Abstract
Visceral fat accumulation has a marked impact on atherosclerotic cardiovascular diseases and metabolic syndrome clustering diabetes, dyslipidemia, and hypertension. Adiponectin, an adipocyte-derived circulating protein, is a representative adipocytokine and uniquely possesses two major properties: 1) its circulating concentration is approximately 3-6 orders of magnitude greater than ordinary hormones and cytokines; 2) its concentration inversely correlates with body fat mass despite its adipocyte-specific production. Low serum levels of adiponectin correlate with cardiometabolic diseases. Extensive experimental evidence has demonstrated that adiponectin possesses multiple properties, such as anti-atherosclerotic, anti-diabetic, and anti-inflammatory activities. It has been shown to play a central role against the development of metabolic syndrome and its complications. However, even approximately 25 years after its discovery, the properties of adiponectin, including how and why it exerts multiple beneficial effects on various tissues and/or organs, remain unclear. Furthermore, the mechanisms responsible for the very high circulating concentrations of adiponectin in the bloodstream have not been elucidated. Several adiponectin-binding partners, such as AdipoR1/2, have been identified, but do not fully explain the multi-functional and beneficial properties of adiponectin. Recent advances in adiponectin research may resolve these issues. Adiponectin binds to and covers cell surfaces with T-cadherin, a unique glycosylphosphatidylinositol (GPI)-anchored cadherin. The adiponectin/T-cadherin complex enhances exosomal production and release, excreting cell-toxic products from cells, particularly in the vasculature. In this review, we discuss adiponectin and the role of the adiponectin/T-cadherin system in the maintenance of whole body homeostasis and cardiovascular protection.
Collapse
Affiliation(s)
- Norikazu Maeda
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamada-oka, Suita, Osaka, 565-0871, Japan; Department of Metabolism and Atherosclerosis, Graduate School of Medicine, Osaka University, 2-2, Yamada-oka, Suita, Osaka, 565-0871, Japan.
| | - Tohru Funahashi
- Division of Osaka Health Support Center, Sumitomo Mitsui Banking Corporation, 6-5, Kitahama 4-chome, Chuo-ku, Osaka, Osaka, 541-0041, Japan
| | - Yuji Matsuzawa
- Department of Endocrinology and Metabolism, Sumitomo Hospital, 5-3-20, Nakanoshima, Kita-ku, Osaka, Osaka, 530-0005, Japan
| | - Iichiro Shimomura
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamada-oka, Suita, Osaka, 565-0871, Japan
| |
Collapse
|
|
16
|
Cornish AJ, Tomlinson IPM, Houlston RS. Mendelian randomisation: A powerful and inexpensive method for identifying and excluding non-genetic risk factors for colorectal cancer. Mol Aspects Med 2019; 69:41-47. [PMID: 30710596 PMCID: PMC6856712 DOI: 10.1016/j.mam.2019.01.002] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 01/28/2019] [Indexed: 12/12/2022]
Abstract
Colorectal cancer (CRC) is the third most common cancer in economically developed countries and a major cause of cancer-related mortality. The importance of lifestyle and diet as major determinants of CRC risk is suggested by differences in CRC incidence between countries and in migration studies. Previous observational epidemiological studies have identified associations between modifiable environmental risk factors and CRC, but these studies can be susceptible to reverse causation and confounding, and their results can therefore conflict. Mendelian randomisation (MR) analysis represents an approach complementary to conventional observational studies examining associations between exposures and disease. The MR strategy employs allelic variants as instrumental variables (IVs), which act as proxies for non-genetic exposures. These allelic variants are randomly assigned during meiosis and can therefore inform on life-long exposure, whilst not being subject to reverse causation. In previous studies MR frameworks have associated several modifiable factors with CRC risk, including adiposity, hyperlipidaemia, fatty acid profile and alcohol consumption. In this review we detail the use of MR to investigate and discover CRC risk factors, and its future applications.
Collapse
Affiliation(s)
- Alex J Cornish
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
| | - Ian P M Tomlinson
- Cancer Genetics and Evolution Laboratory, Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK; Department of Histopathology, University Hospitals Birmingham, Birmingham, UK
| | - Richard S Houlston
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK; Division of Molecular Pathology, The Institute of Cancer Research, London, UK
| |
Collapse
|
|
17
|
Circulating adipokines and risk of obesity related cancers: A systematic review and meta-analysis. Obes Res Clin Pract 2019; 13:329-339. [DOI: 10.1016/j.orcp.2019.03.006] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 03/13/2019] [Accepted: 03/27/2019] [Indexed: 12/21/2022]
|
|
18
|
Zhao X, Zhang Y, Deng L, Wang Y, Li Y, Chen M. The association between Chinese patients' elevated omentin-1 levels, their clinicopathological features, and the risk of colorectal cancer. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2019; 12:2264-2274. [PMID: 31934050 PMCID: PMC6949648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Accepted: 04/18/2019] [Indexed: 06/10/2023]
Abstract
To investigate the association between plasma omentin-1 levels and the risk of colorectal cancer (CRC) and the pathological changes of CRC, a total of 358 colorectal adenocarcinoma patients were included in the experience group, and 286 people were included in the control group. Their levels of omentin-1, adiponectin, visfatin, leptin, and their anthropometric and metabolic parameters were determined, and we analyzed the tertile distributions in the control group, according to the different levels: low, medium, and high. The results showed that the omentin-1 levels in patients with CRC were higher than the levels in the controls [(67.28 ± 32.25) vs (33.16 ± 19.93) ng/mL, P = 0.005]. The patients with the highest concentration of omentin-1 presented significantly higher odds for CRC, adjusted for potential confounding factors for CRC (odds ratio: 5.76; 95% CI 1.81-8.95; P = 0.001). The plasma omentin-1 level in CRC yielded a receiver operating characteristic curve area of 88.4%. The optimal sensitivity and specificity were 81.2% and 69.8% in discriminating CRC from the normal control. A high omentin-1 level was significantly associated the increasing stage of colorectal adenocarcinomas and the depth of invasion (P = 0.005, 0.026, respectively). The present study suggests an increased level of omentin-1 not only was a strong risk factor for CRC but could also represent a potential biomarker for CRC stage progression and CRC diagnosis in Chinese patients.
Collapse
Affiliation(s)
- Xiaotong Zhao
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical UniversityHefei, Anhui, People’s Republic of China
| | - Yaqin Zhang
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical UniversityHefei, Anhui, People’s Republic of China
| | - Lili Deng
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical UniversityHefei, Anhui, People’s Republic of China
| | - Youming Wang
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical UniversityHefei, Anhui, People’s Republic of China
| | - Yongxiang Li
- Division of General Surgery, The First Affiliated Hospital of Anhui Medical UniversityHefei, Anhui, People’s Republic of China
| | - Mingwei Chen
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical UniversityHefei, Anhui, People’s Republic of China
- Institute of Diabetes Prevention and Control, Academy of Traditional Chinese Medicine of Anhui ProvinceHefei, Anhui, People’s Republic of China
| |
Collapse
|
|
19
|
Nimptsch K, Konigorski S, Pischon T. Diagnosis of obesity and use of obesity biomarkers in science and clinical medicine. Metabolism 2019; 92:61-70. [PMID: 30586573 DOI: 10.1016/j.metabol.2018.12.006] [Citation(s) in RCA: 175] [Impact Index Per Article: 29.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Revised: 12/10/2018] [Accepted: 12/20/2018] [Indexed: 12/19/2022]
Abstract
The global epidemic of obesity is a major public health problem today. Obesity increases the risk of many chronic diseases, such as type 2 diabetes, coronary heart disease, and certain types of cancer, and is associated with lower life expectancy. The body mass index (BMI), which is currently used to classify obesity, is only an imperfect measure of abnormal or excessive body fat accumulation. Studies have shown that waist circumference as a measure of fat distribution may improve disease prediction. More elaborate techniques such as magnetic resonance imaging are increasingly available to assess body fat distribution, but these measures are not readily available in routine clinical practice, and health-relevant cut-offs not yet been established. The measurement of biomarkers that reflect the underlying biological mechanisms for the increased disease risk may be an alternative approach to characterize the relevant obesity phenotype. The insulin/insulin-like growth factor (IGF) axis and chronic low-grade inflammation have been identified as major pathways. In addition, specific adipokines such as leptin, adiponectin and resistin have been related to obesity-associated health outcomes. This biomarker research, which is currently further developed with the application of high throughput methods, gives important insights in obesity-related disease etiology and pathophysiological pathways and may be used to better characterize obese persons at high risk of disease development and target disease-causing biomarkers in personalized prevention strategies.
Collapse
Affiliation(s)
- Katharina Nimptsch
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany.
| | - Stefan Konigorski
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany; Digital Health - Machine Learning Group, Hasso-Plattner-Institute for Digital Engineering, Potsdam, Germany
| | - Tobias Pischon
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany; Charité Universitätsmedizin, Berlin, Germany; Berlin Institute of Health, Berlin, Germany; DZHK (German Center for Cardiovascular Research), partner site Berlin, Berlin, Germany
| |
Collapse
|
|
20
|
Eichelmann F, Schulze MB, Wittenbecher C, Menzel J, Weikert C, di Giuseppe R, Biemann R, Isermann B, Fritsche A, Boeing H, Aleksandrova K. Association of Chemerin Plasma Concentration With Risk of Colorectal Cancer. JAMA Netw Open 2019; 2:e190896. [PMID: 30901045 PMCID: PMC6583278 DOI: 10.1001/jamanetworkopen.2019.0896] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
IMPORTANCE Inflammatory processes have been suggested to have an important role in colorectal cancer (CRC) etiology. Chemerin is a recently discovered inflammatory biomarker thought to exert chemotactic, adipogenic, and angiogenic functions. However, its potential link with CRC has not been sufficiently explored. OBJECTIVE To evaluate the prospective association of circulating plasma chemerin concentrations with incident CRC. DESIGN, SETTING, AND PARTICIPANTS Prospective case-cohort study based on 27 548 initially healthy participants from the European Prospective Investigation Into Cancer and Nutrition (EPIC)-Potsdam cohort who were followed for up to 16 years. Baseline study information and samples were collected between August 23, 1994, and September 25, 1998. Recruitment was according to random registry sampling from the geographical area of Potsdam, Germany, and surrounding municipalities. The last date of study follow-up was May 10, 2010. Statistical analysis was conducted in 2018. MAIN OUTCOMES AND MEASURES Incident CRC, colon cancer, and rectal cancer. Baseline chemerin plasma concentrations were measured by enzyme-linked immunosorbent assay. RESULTS A random subcohort of 221 incident CRC cases and 2329 participants free of CRC with available blood sample measurements were included in the analysis. The participants' mean (SD) age was 50 (9) years, 62.1% were female, and 16.5% had a body mass index greater than 30. In multivariable-adjusted Cox proportional hazards regression models taking into account established CRC risk factors, higher chemerin concentrations were associated with a greater risk of CRC, with a hazard ratio (HR) of 1.81 (95% CI, 1.08-3.05; P for trend = .007) for the highest chemerin quartile vs the lowest. Analyses by cancer subsite indicated a stronger association with colon cancer (HR, 2.27; 95% CI, 1.18-4.34 for the highest quartile vs the lowest; P for trend = .005) compared with rectal cancer (HR, 1.27; 95% CI, 0.57-2.85; P for trend = .35). The association was particularly strong for proximal colon cancer (HR, 3.97; 95% CI, 1.51-10.50; P for trend = .001). CONCLUSIONS AND RELEVANCE This study found that the association between chemerin concentration and the risk of incident CRC was linear and independent of established CRC risk factors. Further studies are warranted to evaluate chemerin as a novel immune-inflammatory agent in colorectal carcinogenesis.
Collapse
Affiliation(s)
- Fabian Eichelmann
- Senior Scientist Group Nutrition, Immunity and Metabolism, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam–Rehbrücke (DIfE), Nuthetal, Germany
| | - Matthias B. Schulze
- German Centre for Cardiovascular Research (DZHK), Berlin, Germany
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam–Rehbrücke (DIfE), Nuthetal, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute of Nutritional Science, University of Potsdam, Potsdam, Germany
| | - Clemens Wittenbecher
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam–Rehbrücke (DIfE), Nuthetal, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Juliane Menzel
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam–Rehbrücke (DIfE), Nuthetal, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Department of Food Safety, German Federal Institute for Risk Assessment, Berlin, Germany
| | - Cornelia Weikert
- Department of Food Safety, German Federal Institute for Risk Assessment, Berlin, Germany
- Institute for Social Medicine, Epidemiology and Health Economics, Charité University Medical Center, Berlin, Germany
| | - Romina di Giuseppe
- Institute of Epidemiology, Christian Albrechts University Kiel, Kiel, Germany
| | - Ronald Biemann
- Department of Clinical Chemistry and Pathobiochemistry, Otto von Guericke University Magdeburg, Magdeburg, Germany
| | - Berend Isermann
- Department of Clinical Chemistry and Pathobiochemistry, Otto von Guericke University Magdeburg, Magdeburg, Germany
| | - Andreas Fritsche
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, Department of Internal Medicine, University of Tübingen, Tübingen, Germany
| | - Heiner Boeing
- Department of Epidemiology, German Institute of Human Nutrition Potsdam–Rehbrücke (DIfE), Nuthetal, Germany
| | - Krasimira Aleksandrova
- Senior Scientist Group Nutrition, Immunity and Metabolism, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam–Rehbrücke (DIfE), Nuthetal, Germany
- Institute of Nutritional Science, University of Potsdam, Potsdam, Germany
| |
Collapse
|
|
21
|
Konigorski S, Janke J, Drogan D, Bergmann MM, Hierholzer J, Kaaks R, Boeing H, Pischon T. Prediction of Circulating Adipokine Levels Based on Body Fat Compartments and Adipose Tissue Gene Expression. Obes Facts 2019; 12:590-605. [PMID: 31698359 PMCID: PMC6940469 DOI: 10.1159/000502117] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Accepted: 07/15/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Adipokines are hormones secreted from adipose tissue (AT), and a number of them have been established as risk factors for chronic diseases. However, it is not clear whether and to what extent adiposity, gene expression, and other factors determine their circulating levels. OBJECTIVES To assess to what extent adiposity, as measured by the amount of subcutaneous AT (SAT) and visceral AT (VAT) using magnetic resonance imaging, and gene expression levels in SAT determine plasma concentrations of the adipokines adiponectin, leptin, soluble leptin receptor, resistin, interleukin 6, and fatty acid-binding protein 4 (FABP4). METHODS We performed a cross-sectional analysis of 156 participants from the EPIC Potsdam cohort study and analyzed multiple regression models and partial correlation coefficients. RESULTS For leptin and FABP4 concentrations, 81 and 45% variance were explained by SAT mass, VAT mass, and gene expression in SAT in multivariable regression models. For the remaining adipokines, AT mass and gene expression explained <16% variance of plasma concentrations. Gene expression in SAT was a less important predictor compared to AT mass. SAT mass was a better predictor than VAT mass for leptin (partial correlation r = 0.81, 95% confidence interval 0.75-0.86, vs. r = 0.58, 95% confidence interval 0.46-0.67), while differences between AT compartments were small for the other adipokines. CONCLUSIONS While plasma levels of leptin and FABP4 can be explained in a large and medium part by the amount of AT and SAT gene expression, surprisingly, these predictors explained only little variance for all other investigated adipokines.
Collapse
Affiliation(s)
- Stefan Konigorski
- Molecular Epidemiology Research Group, Max Delbrück Center (MDC) for Molecular Medicine in the Helmholtz Association, Berlin, Germany,
- Machine Learning Research Group, Hasso Plattner Institute for Digital Engineering, Potsdam, Germany,
| | - Jürgen Janke
- Molecular Epidemiology Research Group, Max Delbrück Center (MDC) for Molecular Medicine in the Helmholtz Association, Berlin, Germany
| | - Dagmar Drogan
- AOK Research Institute (WIdO), AOK Bundesverband, Berlin, Germany
| | - Manuela M Bergmann
- Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Nuthetal, Germany
| | - Johannes Hierholzer
- Department of Diagnostic and Interventional Radiology, Clinic Ernst von Bergmann, Potsdam, Germany
| | - Rudolf Kaaks
- Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Heiner Boeing
- Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Nuthetal, Germany
| | - Tobias Pischon
- Molecular Epidemiology Research Group, Max Delbrück Center (MDC) for Molecular Medicine in the Helmholtz Association, Berlin, Germany
- Charité Universitätsmedizin Berlin, Berlin, Germany
- German Center for Cardiovascular Research (DZHK) partner site Berlin, Berlin, Germany
| |
Collapse
|
|
22
|
Lu W, Huang Z, Li N, Liu H. Low circulating total adiponectin, especially its non-high-molecular weight fraction, represents a promising risk factor for colorectal cancer: a meta-analysis. Onco Targets Ther 2018; 11:2519-2531. [PMID: 29765231 PMCID: PMC5942166 DOI: 10.2147/ott.s157255] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Aim The principal goal of this meta-analysis is to test the hypothesis that circulating total adiponectin or certain fractions may represent a promising biological candidate in modulating the risk of colorectal cancer. Methods The processes of paper identification, paper selection and data extraction were accomplished independently by two authors. Effect-size estimates were expressed as weighted mean difference (WMD) and 95% confidence interval (95% CI). A total of 31 papers including 48 qualified studies (7,554 patients with colorectal cancer and 9,798 controls) were meta-analyzed. Results Pooling all studies found that circulating total adiponectin was significantly lower in patients with colorectal cancer than in controls (WMD: −0.76 µg/mL, 95% CI: −1.20 to −0.32, p=0.001), with significant heterogeneity (I2: 94.2%) and low publication bias (Egger’s p=0.336). By adiponectin fractions, the difference in high-molecular weight (HMW) adiponectin was comparable between the two groups (WMD: −0.22 µg/mL, 95% CI: −0.70 to 0.25, p=0.350), while non-HMW adiponectin was significantly lower in patients with colorectal cancer than in controls (WMD: −0.27 µg/mL, 95% CI: −0.35 to −0.19, p<0.001), with marginal heterogeneity (I2: 52.3%). Subgroup analysis revealed that effect-size estimates were heterogeneous when grouping studies by cancer subtype, region, study design, matching status, gender and obesity. Further meta-regression analysis indicated that age and gender were significant potential sources of heterogeneity. The results showed the studied subgroups were not subject to publication bias (Egger’s p<0.1). Conclusion Our data collectively indicate that low circulating total adiponectin, especially its non-HMW fraction, represents a promising risk factor for colorectal cancer. Further studies are needed to explore underlying mechanisms.
Collapse
Affiliation(s)
- Weiqun Lu
- Department of Gastrointestinal Surgery.,Guangzhou Key Laboratory of Translational Medicine on Malignant Tumor Treatment, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Zhiliang Huang
- Department of Gastrointestinal Surgery.,Guangzhou Key Laboratory of Translational Medicine on Malignant Tumor Treatment, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Nan Li
- Department of Gastrointestinal Surgery.,Guangzhou Key Laboratory of Translational Medicine on Malignant Tumor Treatment, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Haiying Liu
- Department of Gastrointestinal Surgery.,Guangzhou Key Laboratory of Translational Medicine on Malignant Tumor Treatment, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, People's Republic of China
| |
Collapse
|
|
23
|
Nimptsch K, Wu K. Is Timing Important? The Role of Diet and Lifestyle during Early Life on Colorectal Neoplasia. CURRENT COLORECTAL CANCER REPORTS 2018; 14:1-11. [PMID: 30140177 PMCID: PMC6101255 DOI: 10.1007/s11888-018-0396-7] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
PURPOSE OF THE REVIEW To summarize the current evidence on the most important dietary and lifestyle factors in colorectal carcinogenesis during different stages of a lifetime with special emphasis on studies investigating exposure during childhood, adolescence and young adulthood. RECENT FINDINGS A number of studies showed that independent of adult obesity, higher body fatness during childhood, adolescence and young adulthood is associated with risk of colorectal cancer later in life. In one large cohort study, the Nurses' Health Study II, adherence to a western pattern diet during adolescence was associated with higher risk of advanced adenoma. The current evidence relating consumption of individual foods and nutrients as well as physical activity during early life to colorectal cancer is sparse and less consistent, at least in part due to limitations in study design, such as sample size, limited data on potential confounders or lack of a validated dietary assessment instrument. SUMMARY As colorectal carcinogenesis is a long process and can take up to several decades to develop, early life risk factors may also be etiologically relevant. The recent rise in early-onset colorectal cancer incidence and mortality in the US, i.e., in individuals younger than 55 years at diagnosis, strongly supports that early life risk factors may influence colorectal carcinogenesis. Considering that the majority of colorectal cancers are preventable, there is an urgent need for well-designed investigations on the role of diet and lifestyle factors throughout the life course and risk of colorectal cancers.
Collapse
Affiliation(s)
- Katharina Nimptsch
- Molecular Epidemiology Research Group, Max Delbrück Center
for Molecular Medicine (MDC), Berlin, Germany
- Department of Nutrition, Harvard T.H. Chan School of Public Health,
Boston, Massachusetts, USA
| | - Kana Wu
- Department of Nutrition, Harvard T.H. Chan School of Public Health,
Boston, Massachusetts, USA
| |
Collapse
|
|
24
|
Schlesinger S, Aleksandrova K, Abar L, Vieria AR, Vingeliene S, Polemiti E, Stevens CAT, Greenwood DC, Chan DSM, Aune D, Norat T. Adult weight gain and colorectal adenomas-a systematic review and meta-analysis. Ann Oncol 2018; 28:1217-1229. [PMID: 28327995 DOI: 10.1093/annonc/mdx080] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background Colorectal adenomas are known as precursors for the majority of colorectal carcinomas. While weight gain during adulthood has been identified as a risk factor for colorectal cancer, the association is less clear for colorectal adenomas. We conducted a systematic review and meta-analysis to quantify the evidence on this association. Methods We searched Medline up to September 2016 to identify observational (prospective, cross-sectional and retrospective) studies on weight gain during adulthood and colorectal adenoma occurrence and recurrence. We conducted meta-analysis on high weight gain versus stable weight, linear and non-linear dose-response meta-analyses to analyze the association. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using a random effects model. Results For colorectal adenoma occurrence, the summary OR was 1.39 (95% CI: 1.17-1.65; I2: 43%, N = 9 studies, cases = 5507) comparing high (midpoint: 17.4 kg) versus stable weight gain during adulthood and with each 5 kg weight gain the odds increased by 7% (2%-11%; I2: 65%, N = 7 studies). Although there was indication of non-linearity (Pnon-linearity < 0.001) there was an increased odds of colorectal adenoma throughout the whole range of weight gain. Three studies were identified investigating the association between weight gain and colorectal adenoma recurrence and data were limited to draw firm conclusions. Conclusions Even a small amount of adult weight gain was related to a higher odds of colorectal adenoma occurrence. Our findings add to the benefits of weight control in adulthood regarding colorectal adenoma occurrence, which might be relevant for early prevention of colorectal cancer.
Collapse
Affiliation(s)
- S Schlesinger
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.,Junior Research Group Systematic Reviews, Institute for Biometrics and Epidemiology, German Diabetes Center, Düsseldorf
| | - K Aleksandrova
- Nutrition, Immunity and Metabolism Start-up Lab, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| | - L Abar
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - A R Vieria
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - S Vingeliene
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - E Polemiti
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - C A T Stevens
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - D C Greenwood
- Division of Epidemiology and Biostatistics, School of Medicine, University of Leeds, Leeds, UK
| | - D S M Chan
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - D Aune
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.,Bjørknes University College, Oslo, Norway
| | - T Norat
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| |
Collapse
|
|
25
|
Wei T, Ye P, Peng X, Wu LL, Yu GY. Circulating adiponectin levels in various malignancies: an updated meta-analysis of 107 studies. Oncotarget 2018; 7:48671-48691. [PMID: 27119501 PMCID: PMC5217047 DOI: 10.18632/oncotarget.8932] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Accepted: 04/16/2016] [Indexed: 01/11/2023] Open
Abstract
Early detection of cancers is challenging for lack of specific biomarkers. Adiponectin is an adipokine predominantly derived from adipocytes and hypoadiponectinemia has been reported to associate with risk of many types of cancers. However, available evidence is controversial. Some studies show that increased adiponectin levels correlate with cancer risk. Therefore, we performed a meta-analysis of the association between circulating adiponectin levels and cancer development. A systematic search of PubMed, EMBASE, Wiley Online Library and Cochrane Library was conducted for eligible studies involving circulating adiponectin and malignancies from inception to August 8, 2015. Standard mean differences (SMDs) with 95% confidence intervals (95% CIs) were calculated by use of a random-effect model. Funnel plot and Egger's linear regression test were conducted to examine the risk of publication bias. 107 studies were included with 19,319 cases and 25,675 controls. The pooled analysis indicated that circulating adiponectin levels were lower in patients with various cancers than in controls, with a pooled SMD of −0.334 μg/ml (95% CI, −0.465 to −0.203, P = 0.000). No evidence of publication bias was observed. Circulating high molecular weight adiponectin levels were also lower in cancer patients than in controls, with a pooled SMD of −0.502 μg/ml (95% CI, −0.957 to −0.047, P = 0.000). This meta-analysis provides further evidence that decreased adiponectin levels is associated with risk of various cancers. Hypoadiponectinemia may represent a useful biomarker for early detection of cancers.
Collapse
Affiliation(s)
- Tai Wei
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China
| | - Peng Ye
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China
| | - Xin Peng
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China
| | - Li-Ling Wu
- Department of Physiology and Pathophysiology, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, and Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, China
| | - Guang-Yan Yu
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China
| |
Collapse
|
|
26
|
Aleksandrova K, Mozaffarian D, Pischon T. Addressing the Perfect Storm: Biomarkers in Obesity and Pathophysiology of Cardiometabolic Risk. Clin Chem 2018; 64:142-153. [DOI: 10.1373/clinchem.2017.275172] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Accepted: 10/25/2017] [Indexed: 02/06/2023]
Abstract
AbstractBACKGROUNDThe worldwide rise of obesity has provoked intensified research to better understand its pathophysiology as a means for disease prevention. Several biomarkers that may reflect various pathophysiological pathways that link obesity and cardiometabolic diseases have been identified over the past decades.CONTENTWe summarize research evidence regarding the role of established and novel obesity-related biomarkers, focusing on recent epidemiological evidence for detrimental associations with cardiometabolic diseases including obesity-related cancer. The reviewed biomarkers include biomarkers of glucose–insulin homeostasis (insulin, insulin-like growth factors, and C-peptide), adipose tissue biomarkers (adiponectin, omentin, apelin, leptin, resistin, and fatty-acid-binding protein-4), inflammatory biomarkers (C-reactive protein, interleukin 6, tumor necrosis factor α), and omics-based biomarkers (metabolites and microRNAs).SUMMARYAlthough the evidence for many classical obesity biomarkers, including adiponectin and C-reactive protein (CRP), in disease etiology has been initially promising, the evidence for a causal role in humans remains limited. Further, there has been little demonstrated ability to improve disease prediction beyond classical risk factors. In the era of “precision medicine,” there is an increasing interest in novel biomarkers, and the extended list of potentially promising biomarkers, such as adipokines, cytokines, metabolites, and microRNAs, implicated in obesity may bring new promise for improved, personalized prevention. To further evaluate the role of obesity-related biomarkers as etiological and early-disease-prediction targets, well-designed studies are needed to evaluate temporal associations, replicate findings, and test clinical utility of novel biomarkers. In particular, studies to determine the therapeutic implications of novel biomarkers beyond established metabolic risk factors are highly warranted.
Collapse
Affiliation(s)
- Krasimira Aleksandrova
- Nutrition, Immunity and Metabolism Start-up Lab, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
| | | | - Tobias Pischon
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
- Charité – Universitätsmedizin Berlin, Berlin, Germany
- MDC/BIH Biobank, Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Berlin Institute of Health (BIH), Berlin, Germany
- German Center for Cardiovascular Research (DZHK), partner site Berlin, Berlin, Germany
| |
Collapse
|
|
27
|
Ortega LS, Bradbury KE, Cross AJ, Morris JS, Gunter MJ, Murphy N. A Prospective Investigation of Body Size, Body Fat Composition and Colorectal Cancer Risk in the UK Biobank. Sci Rep 2017; 7:17807. [PMID: 29259258 PMCID: PMC5736687 DOI: 10.1038/s41598-017-17997-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2017] [Accepted: 12/04/2017] [Indexed: 12/26/2022] Open
Abstract
Obesity has been consistently associated with a greater colorectal cancer risk, but this relationship is weaker among women. In the UK Biobank, we investigated the associations between body size (body mass index [BMI], height, waist circumference, and waist-to-hip ratio) and body fat composition (total body fat percentage and trunk fat percentage) measurements with colorectal cancer risk among 472,526 men and women followed for 5.6 years on average. Multivariable hazard ratios (HRs) and 95% confidence intervals (95%CI) for developing colorectal cancer (2,636 incident cases) were estimated using Cox proportional hazards models. Among men, when the highest and lowest fifths were compared, BMI (HR = 1.35, 95%CI: 1.13-1.61; Ptrend < 0.0001), waist circumference (HR = 1.66, 95%CI: 1.39-1.99; Ptrend < 0.0001), waist-to-hip ratio (HR = 1.58, 95%CI: 1.31-1.91; Ptrend < 0.0001), total body fat percentage (HR = 1.27, 95%CI: 1.06-1.53; Ptrend = 0.002), and trunk fat percentage (HR = 1.31, 95%CI: 1.09-1.58; Ptrend = 0.002) were associated with greater colorectal cancer risk. For women, only waist-to-hip ratio (HR for highest versus lowest fifth = 1.33, 95%CI: 1.08-1.65; Ptrend = 0.005) was positively associated with colorectal cancer risk. Greater body size (overall and abdominal adiposity) was positively associated with colorectal cancer development in men. For women, abdominal adiposity, rather than overall body size, was associated with a greater colorectal cancer risk.
Collapse
Affiliation(s)
- Luisa Saldana Ortega
- Primary Care Clinical Trials Unit, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
| | - Kathryn E Bradbury
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Amanda J Cross
- School of Public Health, Imperial College London, London, UK
| | | | - Marc J Gunter
- Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France
| | - Neil Murphy
- Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
| |
Collapse
|
|
28
|
Aleksandrova K, Jenab M, Leitzmann M, Bueno-de-Mesquita B, Kaaks R, Trichopoulou A, Bamia C, Lagiou P, Rinaldi S, Freisling H, Carayol M, Pischon T, Drogan D, Weiderpass E, Jakszyn P, Overvad K, Dahm CC, Tjønneland A, Bouton-Ruault MC, Kühn T, Peppa E, Valanou E, La Vecchia C, Palli D, Panico S, Sacerdote C, Agnoli C, Tumino R, May A, van Vulpen J, Benjaminsen Borch K, Oluwafemi Oyeyemi S, Quirós JR, Bonet C, Sánchez MJ, Dorronsoro M, Navarro C, Barricarte A, van Guelpen B, Wennberg P, Key TJ, Khaw KT, Wareham N, Assi N, Ward HA, Aune D, Riboli E, Boeing H. Physical activity, mediating factors and risk of colon cancer: insights into adiposity and circulating biomarkers from the EPIC cohort. Int J Epidemiol 2017; 46:1823-1835. [PMID: 29025032 PMCID: PMC6241846 DOI: 10.1093/ije/dyx174] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/08/2017] [Indexed: 12/11/2022] Open
Abstract
Background There is convincing evidence that high physical activity lowers the risk of colon cancer; however, the underlying biological mechanisms remain largely unknown. We aimed to determine the extent to which body fatness and biomarkers of various biologically plausible pathways account for the association between physical activity and colon cancer. Methods We conducted a nested case-control study in a cohort of 519 978 men and women aged 25 to 70 years followed from 1992 to 2003. A total of 713 incident colon cancer cases were matched, using risk-set sampling, to 713 controls on age, sex, study centre, fasting status and hormonal therapy use. The amount of total physical activity during the past year was expressed in metabolic equivalent of task [MET]-h/week. Anthropometric measurements and blood samples were collected at study baseline. Results High physical activity was associated with a lower risk of colon cancer: relative risk ≥91 MET-h/week vs <91 MET-h/week = 0.75 [95% confidence interval (CI): 0.57 to 0.96]. In mediation analyses, this association was accounted for by waist circumference: proportion explained effect (PEE) = 17%; CI: 4% to 52%; and the biomarkers soluble leptin receptor (sOB-R): PEE = 15%; 95% CI: 1% to 50% and 5-hydroxyvitamin D (25[OH]D): PEE = 30%; 95% CI: 12% to 88%. In combination, these factors explained 45% (95% CI: 20% to 125%) of the association. Beyond waist circumference, sOB-R and 25[OH]D additionally explained 10% (95% CI: 1%; 56%) and 23% (95% CI: 6%; 111%) of the association, respectively. Conclusions Promoting physical activity, particularly outdoors, and maintaining metabolic health and adequate vitamin D levels could represent a promising strategy for colon cancer prevention.
Collapse
Affiliation(s)
- Krasimira Aleksandrova
- Nutrition, Immunity and Metabolism Start-up Lab, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| | - Mazda Jenab
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Michael Leitzmann
- Department of Epidemiology and Preventive Medicine, Regensburg University Medical Center, Regensburg, Germany
| | - Bas Bueno-de-Mesquita
- National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
- Department of Gastroenterology and Hepatology, University Medical Center, Utrecht, the Netherlands
- Division of Epidemiology, Public Health and Primary Care, Imperial College, London, United Kingdom
- Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Rudolf Kaaks
- Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany
| | - Antonia Trichopoulou
- Hellenic Health Foundation, Athens, Greece
- WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, National and Kapodistrian University of Athens (NKUA), Medical School, Athens, Greece
| | - Christina Bamia
- Hellenic Health Foundation, Athens, Greece
- WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, National and Kapodistrian University of Athens (NKUA), Medical School, Athens, Greece
| | - Pagona Lagiou
- Hellenic Health Foundation, Athens, Greece
- Department of Epidemiology, Harvard School of Public Health, Boston, USA
| | - Sabina Rinaldi
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Heinz Freisling
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Marion Carayol
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Tobias Pischon
- Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany
| | - Dagmar Drogan
- Quality and Health Services Research Unit, AOK Research Institute, Berlin, Germany (DD)
| | - Elisabete Weiderpass
- Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
- Department of Research, Cancer Registry of Norway, Oslo, Norway
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Genetic Epidemiology Group, Folkhalsan Research Center, Helsinki, Finland
| | - Paula Jakszyn
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, Barcelona, Spain
| | - Kim Overvad
- Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark
| | - Christina C Dahm
- Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark
| | - Anne Tjønneland
- Diet, Genes and Environment, Danish Cancer Society Research Center Copenhagen, Denmark
| | - Marie-Christine Bouton-Ruault
- Inserm, Centre for research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health team,F-94805, Villejuif, France
- Univ Paris Sud, UMRS 1018, F-94805, Villejuif, France
- IGR, F-94805, Villejuif, France
| | - Tilman Kühn
- German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany
| | | | | | - Carlo La Vecchia
- Hellenic Health Foundation, Athens, Greece
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano
| | - Domenico Palli
- Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy
| | - Salvatore Panico
- Department of clinical and experimental medicine-Federico II University, Naples, Italy
| | - Carlotta Sacerdote
- Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy
| | - Claudia Agnoli
- Epidemiology and Prevention Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy
| | - Rosario Tumino
- Cancer Registry and Histopathology Unit, “M.P.Arezzo” Hospital, Ragusa, Italy
| | - Anne May
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht
| | - Jonna van Vulpen
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht
| | - Kristin Benjaminsen Borch
- Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
| | - Sunday Oluwafemi Oyeyemi
- Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
| | | | - Catalina Bonet
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, Barcelona, Spain
| | - María-José Sánchez
- Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Granada, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Spain
| | - Miren Dorronsoro
- Epidemiology and Health Information, Public Health Division of Gipuzkoa, Basque Regional Health Department, San Sebastian, Spain
| | - Carmen Navarro
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Spain
- Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain
- Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain
| | - Aurelio Barricarte
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Spain
- Navarre Public Health Institute, Pamplona, Navarra, Spain
- Navarra Institute for Health Research (IdiSNA) Pamplona, Spain
| | | | - Patrik Wennberg
- Department of Public Health and Clinical Medicine, Family Medicine, Umeå University, Umeå, Sweden
| | - Timothy J Key
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford
| | - Kay-Tee Khaw
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Nicholas Wareham
- MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, United Kingdom
| | - Nada Assi
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Heather A Ward
- Division of Epidemiology, Public Health and Primary Care, Imperial College, London, United Kingdom
| | - Dagfinn Aune
- Division of Epidemiology, Public Health and Primary Care, Imperial College, London, United Kingdom
| | - Elio Riboli
- Division of Epidemiology, Public Health and Primary Care, Imperial College, London, United Kingdom
| | - Heiner Boeing
- Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| |
Collapse
|
|
29
|
Aleksandrova K, Schlesinger S, Fedirko V, Jenab M, Bueno-de-Mesquita B, Freisling H, Romieu I, Pischon T, Kaaks R, Gunter MJ, Dahm CC, Overvad K, Rostgaard-Hansen AL, Tjønneland A, Trichopoulou A, Bamia C, Lagiou P, Agnoli C, Mattiello A, Bradbury K, Khaw KT, Riboli E, Boeing H. Metabolic Mediators of the Association Between Adult Weight Gain and Colorectal Cancer: Data From the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort. Am J Epidemiol 2017; 185:751-764. [PMID: 28387787 DOI: 10.1093/aje/kww194] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2015] [Accepted: 04/01/2016] [Indexed: 12/28/2022] Open
Abstract
Evidence indicates that gaining weight in adult life is associated with an elevated risk of colorectal cancer; however, biological mechanisms that may explain this association remain unclear. We evaluated the mediation effect of 20 different biomarkers on the relationship between adult weight gain and colorectal cancer, using data from a prospective nested case-control study of 452 incident cases diagnosed between 1992 and 2003 and matched within risk sets to 452 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The proportions of mediated effects (%) were estimated on the basis of differences in percent effect changes in conditional logistic regression models with and without additional adjustment for individual biomarkers. Greater adult weight gain (≥300 g/year vs. <300 g/year) was associated with a higher risk of colon cancer (multivariable-adjusted relative risk = 1.54, 95% confidence interval: 1.07, 2.24) but not rectal cancer (relative risk = 1.07, 95% confidence interval: 0.68, 1.66). This association was accounted for mostly by attained waist circumference (reduction of 61%) and by the biomarkers soluble leptin receptor (reduction of 43%) and glycated hemoglobin (reduction of 28%). These novel data suggest that the observed association between adult weight gain and colon cancer could be primarily explained by attained abdominal fatness and biomarkers of metabolic dysfunction.
Collapse
|
|
30
|
Nimptsch K, Song M, Aleksandrova K, Katsoulis M, Freisling H, Jenab M, Gunter MJ, Tsilidis KK, Weiderpass E, Bueno-De-Mesquita HB, Chong DQ, Jensen MK, Wu C, Overvad K, Kühn T, Barrdahl M, Melander O, Jirström K, Peeters PH, Sieri S, Panico S, Cross AJ, Riboli E, Van Guelpen B, Myte R, Huerta JM, Rodriguez-Barranco M, Quirós JR, Dorronsoro M, Tjønneland A, Olsen A, Travis R, Boutron-Ruault MC, Carbonnel F, Severi G, Bonet C, Palli D, Janke J, Lee YA, Boeing H, Giovannucci EL, Ogino S, Fuchs CS, Rimm E, Wu K, Chan AT, Pischon T. Genetic variation in the ADIPOQ gene, adiponectin concentrations and risk of colorectal cancer: a Mendelian Randomization analysis using data from three large cohort studies. Eur J Epidemiol 2017; 32:419-430. [PMID: 28550647 PMCID: PMC5535815 DOI: 10.1007/s10654-017-0262-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2016] [Accepted: 05/18/2017] [Indexed: 12/20/2022]
Abstract
Higher levels of circulating adiponectin have been related to lower risk of colorectal cancer in several prospective cohort studies, but it remains unclear whether this association may be causal. We aimed to improve causal inference in a Mendelian Randomization meta-analysis using nested case-control studies of the European Prospective Investigation into Cancer and Nutrition (EPIC, 623 cases, 623 matched controls), the Health Professionals Follow-up Study (HPFS, 231 cases, 230 controls) and the Nurses' Health Study (NHS, 399 cases, 774 controls) with available data on pre-diagnostic adiponectin concentrations and selected single nucleotide polymorphisms in the ADIPOQ gene. We created an ADIPOQ allele score that explained approximately 3% of the interindividual variation in adiponectin concentrations. The ADIPOQ allele score was not associated with risk of colorectal cancer in logistic regression analyses (pooled OR per score-unit unit 0.97, 95% CI 0.91, 1.04). Genetically determined twofold higher adiponectin was not significantly associated with risk of colorectal cancer using the ADIPOQ allele score as instrumental variable (pooled OR 0.73, 95% CI 0.40, 1.34). In a summary instrumental variable analysis (based on previously published data) with higher statistical power, no association between genetically determined twofold higher adiponectin and risk of colorectal cancer was observed (0.99, 95% CI 0.93, 1.06 in women and 0.94, 95% CI 0.88, 1.01 in men). Thus, our study does not support a causal effect of circulating adiponectin on colorectal cancer risk. Due to the limited genetic determination of adiponectin, larger Mendelian Randomization studies are necessary to clarify whether adiponectin is causally related to lower risk of colorectal cancer.
Collapse
Affiliation(s)
- Katharina Nimptsch
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany.
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
| | - Mingyang Song
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Krasimira Aleksandrova
- Nutrition, Immunity and Metabolism Start-up Lab, Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbruecke, Nuthetal, Germany
| | - Michail Katsoulis
- Hellenic Health Foundation, Athens, Greece
- Farr Institute of Health Informatics Research at London, UCL, London, UK
| | - Heinz Freisling
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Mazda Jenab
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Marc J Gunter
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Konstantinos K Tsilidis
- Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, UK
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | - Elisabete Weiderpass
- Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
- Department of Research, Cancer Registry of Norway, Oslo, Norway
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Samfundet Folkhälsan, Helsinki, Finland
| | - H Bas Bueno-De-Mesquita
- Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, UK
- Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
- Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Dawn Q Chong
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Majken K Jensen
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
| | - Chunsen Wu
- Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
- Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
- Odense University Hospital, Odense, Denmark
| | - Kim Overvad
- Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
| | - Tilman Kühn
- Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
| | - Myrto Barrdahl
- Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
| | - Olle Melander
- Department of Clinical Sciences Lund, Lund University, Malmö, Sweden
| | - Karin Jirström
- Department of Clinical Sciences Lund, Lund University, Malmö, Sweden
| | - Petra H Peeters
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
- MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK
| | - Sabina Sieri
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Salvatore Panico
- Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
| | - Amanda J Cross
- Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, UK
| | - Elio Riboli
- Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, UK
| | | | - Robin Myte
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
| | - José María Huerta
- Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain
- CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - Miguel Rodriguez-Barranco
- CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs, GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain
| | | | - Miren Dorronsoro
- Public Health Direction and Biodonostia Research Institute- Ciberesp, Basque Regional Health Department, San Sebastian, Spain
| | | | - Anja Olsen
- Danish Cancer Society Research Center, Copenhagen, Denmark
| | - Ruth Travis
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Marie-Christine Boutron-Ruault
- Université Paris-Sud, UVSQ, CESP, INSERM, Université Paris-Saclay, Villejuif, France
- Gustave Roussy, 94805, Villejuif, France
| | - Franck Carbonnel
- Université Paris-Sud, UVSQ, CESP, INSERM, Université Paris-Saclay, Villejuif, France
- Gustave Roussy, 94805, Villejuif, France
- Department of Gastroenterology, Assistance Publique-Hôpitaux de Paris (AP-HP), University hospitals Paris-Sud, Site de Bicêtre, Paris Sud University, Paris XI, Le Kremlin Bicêtre, Villejuif, France
| | - Gianluca Severi
- Université Paris-Sud, UVSQ, CESP, INSERM, Université Paris-Saclay, Villejuif, France
- Gustave Roussy, 94805, Villejuif, France
- Human Genetics Foundation (HuGeF), Turin, Italy
- Cancer Council Victoria, Melbourne, Australia
- University of Melbourne, Melbourne, Australia
| | - Catalina Bonet
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO), Barcelona, Spain
| | - Domenico Palli
- Cancer Research and Prevention Institute (ISPO), Florence, Italy
| | - Jürgen Janke
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany
| | - Young-Ae Lee
- Genetics of Allergic Disease Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany
| | - Heiner Boeing
- Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbruecke, Nuthetal, Germany
| | - Edward L Giovannucci
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
| | - Shuji Ogino
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
- Division of MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
| | - Charles S Fuchs
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Eric Rimm
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
| | - Kana Wu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Andrew T Chan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
- Broad Institute, Cambridge, MA, USA
| | - Tobias Pischon
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany
- Charité Universitätsmedizin, Berlin, Germany
| |
Collapse
|
|
31
|
|
|
32
|
Murphy N, Falk RT, Messinger DB, Pollak M, Xue X, Lin J, Sgueglia R, Strickler HD, Gaudet MM, Gunter MJ. Influence of Fasting Status and Sample Preparation on Metabolic Biomarker Measurements in Postmenopausal Women. PLoS One 2016; 11:e0167832. [PMID: 27930694 PMCID: PMC5145182 DOI: 10.1371/journal.pone.0167832] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Accepted: 11/21/2016] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Epidemiologic data linking metabolic markers-such as insulin, insulin-like growth factors (IGFs)-and adipose tissue-derived factors with cancer are inconsistent. Between-study differences in blood collection protocols, in particular participant's fasting status, may influence measurements. METHODS We investigated the impact of fasting status and blood sample processing time on components of the insulin/IGF axis and in adipokines in a controlled feeding study of 45 healthy postmenopausal-women aged 50-75 years. Fasting blood samples were drawn (T0), after which subjects ate a standardized breakfast; subsequent blood draws were made at 1 hour (T1), 3 hours (T3), and 6 hours (T6) after breakfast. Serum samples were assayed for insulin, C-peptide, total- and free-IGF-I, IGF-binding protein [BP]-1 and -3, total and high molecular weight (HMW)-adiponectin, retinol binding protein-4, plasminogen activator inhibitor (PAI)-1, and resistin. RESULTS Insulin and C-peptide levels followed similar postprandial trajectories; intra-class correlation coefficients [ICC] for insulin = 0.75, (95%CI:0.64-0.97) and C-peptide (ICC = 0.66, 95%CI:0.54-0.77) were similarly correlated in fasting (Spearman correlation, r = 0.78, 95%CI:0.64-0.88) and postprandial states (T1, r = 0.77 (95%CI: 0.62-0.87); T3,r = 0.78 (95%CI: 0.63-0.87); T6,r = 0.77 (95%CI: 0.61-0.87)). Free-IGF-I and IGFBP-1 levels were also affected by fasting status, whereas total-IGF-I and IGFBP-3 levels remained unchanged. Levels of adipokines were largely insensitive to fasting status and blood sample processing delays. CONCLUSION Several components of the insulin/IGF axis were significantly impacted by fasting state and in particular, C-peptide levels were substantially altered postprandially and in a similar manner to insulin.
Collapse
Affiliation(s)
- Neil Murphy
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
- International Agency for Research on Cancer, Lyon, France
| | - Roni T. Falk
- Division of Cancer Epidemiology and Genetics, Hormonal and Reproductive Epidemiology Branch, National Cancer Institute, Bethesda, Maryland, United States of America
| | - Diana B. Messinger
- The Rockefeller University Hospital, New York, New York, United States of America
| | - Michael Pollak
- Department of Oncology, McGill University, Montreal, Quebec, Canada
| | - Xiaonan Xue
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America
| | - Juan Lin
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America
| | - Robin Sgueglia
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America
| | - Howard D. Strickler
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America
| | - Mia M. Gaudet
- Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, United States of America
| | - Marc J. Gunter
- International Agency for Research on Cancer, Lyon, France
| |
Collapse
|
|
33
|
Eichelmann F, Schwingshackl L, Fedirko V, Aleksandrova K. Effect of plant-based diets on obesity-related inflammatory profiles: a systematic review and meta-analysis of intervention trials. Obes Rev 2016; 17:1067-1079. [PMID: 27405372 DOI: 10.1111/obr.12439] [Citation(s) in RCA: 136] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Revised: 05/11/2016] [Accepted: 05/23/2016] [Indexed: 12/24/2022]
Abstract
Plant-based dietary interventions have been proposed to reduce obesity induced chronic low-grade inflammation and hence prevent chronic disease risk; however, human evidence remains unclear. This systematic review and meta-analysis of intervention trials aimed to assess the effect of plant-based diets on obesity-related inflammatory biomarker profiles. Medline, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for articles published until January 2016 and mean differences in biomarkers of inflammatory status were assessed for: C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-ɑ), soluble intercellular adhesion molecule 1 (sICAM), leptin, adiponectin and resistin. Of initially identified 2,583 publications, 29 met the meta-analysis inclusion criteria [a total of 2,689 participants]. Consumption of plant-based diets was associated with a reduction in the mean concentrations of the following biomarkers: CRP [effect size, -0.55 mg/l, 95% confidence intervals (CI): -0.78; -0.32, I2 = 94.4%], IL-6 [effect size, -0.25 ng/l, 95% CI: -0.56; 0.06, I2 = 74%], and, to some degree, sICAM (-25.07 ng/ml [95% CI: -52.32; 2.17, I2 = 93.2%]). No substantial effects were revealed for TNF-ɑ, resistin, adiponectin and leptin. Plant-based diets are associated with an improvement in obesity-related inflammatory profiles and could provide means for therapy and prevention of chronic disease risk.
Collapse
Affiliation(s)
- F Eichelmann
- Nutrition, Immunity and Metabolism Start-up Lab, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| | - L Schwingshackl
- Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| | - V Fedirko
- Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, USA
| | - K Aleksandrova
- Nutrition, Immunity and Metabolism Start-up Lab, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
| |
Collapse
|
|
34
|
Beg MS, Saleem S, Turer A, Ayers C, de Lemos JA, Khera A, Scherer PE, Lakoski SG. A Prospective Analysis of Plasma Adiponectin and Risk of Incident Cancer: The Dallas Heart Study. J Natl Compr Canc Netw 2016; 13:873-8. [PMID: 26150581 DOI: 10.6004/jnccn.2015.0104] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Adiponectin dysregulation is postulated to affect cancer risk via modulation of insulin resistance and inflammation. Epidemiologic studies evaluating this relationship have conflicting results and data from non-white cohorts are lacking. We examined the association between adiponectin and risk of cancer incidence in the multiethnic Dallas Heart Study (DHS). METHODS Participants enrolled in the DHS and known adiponectin values were included. Incident cancer cases were identified through a systematic linkage of the DHS and the Texas Cancer Registry. Univariate/multivariate analysis were performed to test the association between adiponectin and incident cancer after adjusting for age, diabetes status, gender, ethnicity, C-reactive protein level, smoking status, and body mass index. Adiponectin level was evaluated both as a continuous variable and in race/ethnicity specific quartiles. RESULTS Of 3444 individuals, there were 152 incident cancers. The study population was comprised of 44.4% men, and 51.05% were black. Baseline median adiponectin levels were 6.43 mcg/mL (interquartile range [IQR], 4.37-9.45 mcg/mL) in the incident cancer group versus 6.33 mcg/mL (IQR, 4.57-9.97 mcg/mL) in those without cancer. In multivariable analysis, adiponectin level was not associated with cancer incidence after adjusting for covariates. In analyses stratified by race/ethnic group, no association was observed in white, Hispanic, or African American subgroups. CONCLUSIONS In this study of a predominant ethnic minority population, no association between adiponectin and cancer incidence was demonstrated. Despite preclinical rationale and confirmatory findings in other studies, this association may not replicate across all ethnic populations. Additional studies with strong minority representation are warranted to further examine this association.
Collapse
Affiliation(s)
- Muhammad Shaalan Beg
- From the Department of Internal Medicine, Division of Hematology/Oncology, UT Southwestern Medical Center, Dallas; Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston; Department of Internal Medicine, Division of Cardiology, UT Southwestern Medical Center, Dallas, and Department of Internal Medicine, Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, Texas; and the Division of Hematology/Oncology, Vermont Cancer Center, University of Vermont, Burlington, Vermont
| | - Sadia Saleem
- From the Department of Internal Medicine, Division of Hematology/Oncology, UT Southwestern Medical Center, Dallas; Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston; Department of Internal Medicine, Division of Cardiology, UT Southwestern Medical Center, Dallas, and Department of Internal Medicine, Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, Texas; and the Division of Hematology/Oncology, Vermont Cancer Center, University of Vermont, Burlington, Vermont
| | - Aslan Turer
- From the Department of Internal Medicine, Division of Hematology/Oncology, UT Southwestern Medical Center, Dallas; Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston; Department of Internal Medicine, Division of Cardiology, UT Southwestern Medical Center, Dallas, and Department of Internal Medicine, Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, Texas; and the Division of Hematology/Oncology, Vermont Cancer Center, University of Vermont, Burlington, Vermont
| | - Colby Ayers
- From the Department of Internal Medicine, Division of Hematology/Oncology, UT Southwestern Medical Center, Dallas; Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston; Department of Internal Medicine, Division of Cardiology, UT Southwestern Medical Center, Dallas, and Department of Internal Medicine, Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, Texas; and the Division of Hematology/Oncology, Vermont Cancer Center, University of Vermont, Burlington, Vermont
| | - James A de Lemos
- From the Department of Internal Medicine, Division of Hematology/Oncology, UT Southwestern Medical Center, Dallas; Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston; Department of Internal Medicine, Division of Cardiology, UT Southwestern Medical Center, Dallas, and Department of Internal Medicine, Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, Texas; and the Division of Hematology/Oncology, Vermont Cancer Center, University of Vermont, Burlington, Vermont
| | - Amit Khera
- From the Department of Internal Medicine, Division of Hematology/Oncology, UT Southwestern Medical Center, Dallas; Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston; Department of Internal Medicine, Division of Cardiology, UT Southwestern Medical Center, Dallas, and Department of Internal Medicine, Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, Texas; and the Division of Hematology/Oncology, Vermont Cancer Center, University of Vermont, Burlington, Vermont
| | - Philipp E Scherer
- From the Department of Internal Medicine, Division of Hematology/Oncology, UT Southwestern Medical Center, Dallas; Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston; Department of Internal Medicine, Division of Cardiology, UT Southwestern Medical Center, Dallas, and Department of Internal Medicine, Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, Texas; and the Division of Hematology/Oncology, Vermont Cancer Center, University of Vermont, Burlington, Vermont
| | - Susan G Lakoski
- From the Department of Internal Medicine, Division of Hematology/Oncology, UT Southwestern Medical Center, Dallas; Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston; Department of Internal Medicine, Division of Cardiology, UT Southwestern Medical Center, Dallas, and Department of Internal Medicine, Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, Texas; and the Division of Hematology/Oncology, Vermont Cancer Center, University of Vermont, Burlington, Vermont
| |
Collapse
|
|
35
|
Otani K, Ishihara S, Yamaguchi H, Murono K, Yasuda K, Nishikawa T, Tanaka T, Kiyomatsu T, Hata K, Kawai K, Nozawa H, Watanabe T. Adiponectin and colorectal cancer. Surg Today 2016; 47:151-158. [PMID: 27061803 DOI: 10.1007/s00595-016-1334-4] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2015] [Accepted: 02/16/2016] [Indexed: 12/21/2022]
Abstract
Colorectal cancer is an obesity-related malignancy. Adiponectin is an adipokine produced exclusively by adipose tissue, and its concentration in the serum is reduced in obesity. A low serum level of adiponectin is associated with an increased risk of various types of malignancies including colorectal cancer. These facts suggest that the epidemiological link between obesity and cancer may have a significant association with adiponectin. Although numerous studies of colorectal cancer have been reported, the results are conflicting about the anti-cancer effect of adiponectin, and how adiponectin affects carcinogenesis or cancer development remains controversial. Because adiponectin has multiple systemic effects and exists as a high serum concentration protein, the main role of adiponectin should be regulation of homeostasis, and it would not likely act as an anti-cancerous hormone. However, as epidemiological evidence shows, a low adiponectin level may be a basic risk factor for colorectal cancer. We speculate that when the colonic epithelium is stimulated or damaged by another carcinogen under the condition of a low adiponectin level, carcinogenesis is promoted and cancer development is facilitated. In this report, we summarize recent findings of the correlation between adiponectin and colorectal cancer and investigate the effect of adiponectin on colorectal cancer.
Collapse
Affiliation(s)
- Kensuke Otani
- Department of Surgical Oncology, The University of Tokyo, Hongo7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Soichiro Ishihara
- Department of Surgical Oncology, The University of Tokyo, Hongo7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Hironori Yamaguchi
- Department of Surgical Oncology, The University of Tokyo, Hongo7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Koji Murono
- Department of Surgical Oncology, The University of Tokyo, Hongo7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Koji Yasuda
- Department of Surgical Oncology, The University of Tokyo, Hongo7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Takeshi Nishikawa
- Department of Surgical Oncology, The University of Tokyo, Hongo7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Toshiaki Tanaka
- Department of Surgical Oncology, The University of Tokyo, Hongo7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Tomomichi Kiyomatsu
- Department of Surgical Oncology, The University of Tokyo, Hongo7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Keisuke Hata
- Department of Surgical Oncology, The University of Tokyo, Hongo7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Kazushige Kawai
- Department of Surgical Oncology, The University of Tokyo, Hongo7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Hiroaki Nozawa
- Department of Surgical Oncology, The University of Tokyo, Hongo7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Toshiaki Watanabe
- Department of Surgical Oncology, The University of Tokyo, Hongo7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan
| |
Collapse
|
|
36
|
Nimptsch K, Pischon T. Obesity Biomarkers, Metabolism and Risk of Cancer: An Epidemiological Perspective. Recent Results Cancer Res 2016; 208:199-217. [PMID: 27909909 DOI: 10.1007/978-3-319-42542-9_11] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Obesity is associated with metabolic alterations that may pose a biological link between body fatness and risk of cancer. Elucidating the role of obesity-related biomarkers in cancer development is essential for developing targeted strategies aiming at obesity-associated cancer prevention. Molecular epidemiological studies of the past decades have provided evidence that major hormonal pathways linking obesity and cancer risk include the insulin and insulin-like growth factor-1 (IGF-1) axis, sex-steroid hormones, adipokines and chronic low-grade inflammation. These pathways are interrelated with each other, and their importance varies by obesity-related cancer type. The insulin/IGF-1 axis has been implicated to play an important mediating role in the association between obesity and risk of pancreatic, colorectal and prostate cancer. Endogenous sex-steroid hormone concentrations, in particular obesity-associated pre-diagnostic elevations of estrogens and androgens, play an important role in postmenopausal breast cancer and endometrial cancer development. The adipokines adiponectin and leptin and adipocyte-mediated chronic low-grade inflammation represented by the acute-phase C-reactive protein may explain a substantial part of the association between obesity and risk of colorectal cancer. There is less evidence on whether these hormonal pathways play a mediating role in other obesity-associated types of cancer. In this chapter, the molecular epidemiologic evidence from prospective studies relating circulating obesity-related biomarkers to cancer risk is summarized, taking into account available evidence from Mendelian Randomization investigations aiming at improving causal inference.
Collapse
Affiliation(s)
- Katharina Nimptsch
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany.
| | - Tobias Pischon
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany
| |
Collapse
|
|
37
|
Inamura K, Song M, Jung S, Nishihara R, Yamauchi M, Lochhead P, Qian ZR, Kim SA, Mima K, Sukawa Y, Masuda A, Imamura Y, Zhang X, Pollak MN, Mantzoros CS, Harris CC, Giovannucci E, Fuchs CS, Cho E, Chan AT, Wu K, Ogino S. Prediagnosis Plasma Adiponectin in Relation to Colorectal Cancer Risk According to KRAS Mutation Status. J Natl Cancer Inst 2015; 108:djv363. [PMID: 26598515 DOI: 10.1093/jnci/djv363] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2014] [Accepted: 10/27/2015] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Low levels of adiponectin (ADIPOQ; HGNC ID; HGNC:13633), an adipokine, are associated with obesity, adiposity, excess energy balance, and increased risk of colorectal neoplasia. Given the reported association of increased body mass index (BMI) and low-level physical activity with KRAS-mutated colorectal tumor, we hypothesized that low-level plasma adiponectin might be associated with increased risk of KRAS-mutant colorectal carcinoma but not with risk of KRAS wild-type carcinoma. METHODS We conducted molecular pathological epidemiology research using a nested case-control study design (307 incident rectal and colon cancer case patients and 593 matched control individuals) within prospective cohort studies, the Nurses' Health Study (152 case patients and 297 control individuals, with blood collection in 1989-1990) and the Health Professionals Follow-up Study (155 case patients and 296 control individuals, with blood collection in 1993-1995). Multivariable conditional logistic regression models and two-sided likelihood ratio tests were used to assess etiologic heterogeneity of the associations. RESULTS The association of low-level plasma adiponectin with colorectal cancer risk statistically significantly differed by KRAS mutation status (P heterogeneity = .004). Low levels of plasma adiponectin were associated with KRAS-mutant colorectal cancer (for the lowest vs highest tertile: multivariable odds ratio [OR] = 2.83, 95% confidence interval [CI] = 1.50 to 5.34, P trend = .002) but not with KRAS wild-type cancer (for the lowest vs highest tertile: multivariable OR = 0.83, 95% CI = 0.49 to 1.43, P trend = .48). In secondary analyses, the association between plasma adiponectin and colorectal cancer did not appreciably differ by BRAF or PIK3CA oncogene mutation status. CONCLUSIONS Low-level plasma adiponectin is associated with KRAS-mutant colorectal cancer risk but not with KRAS wild-type cancer risk.
Collapse
Affiliation(s)
- Kentaro Inamura
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (KI, RN, MY, PL, ZRQ, SAK, KM, YS, YI, CSF, SO); Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD (KI, CCH); Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan (KI); Department of Nutrition (MS, RN, EG, KW), Department of Epidemiology (MS, EG, SO), and Department of Biostatistics (RN), Harvard T. H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine (SJ, XZ, EG, CSF, EC, ATC) and Department of Pathology (SO), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA (PL, ATC); Department of Oncology, McGill University, Montreal, Quebec, Canada (MNP); Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (CSM); Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA (CSM); Department of Dermatology, Warren Alpert Medical School of Brown University, Province, RI (EC)
| | - Mingyang Song
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (KI, RN, MY, PL, ZRQ, SAK, KM, YS, YI, CSF, SO); Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD (KI, CCH); Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan (KI); Department of Nutrition (MS, RN, EG, KW), Department of Epidemiology (MS, EG, SO), and Department of Biostatistics (RN), Harvard T. H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine (SJ, XZ, EG, CSF, EC, ATC) and Department of Pathology (SO), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA (PL, ATC); Department of Oncology, McGill University, Montreal, Quebec, Canada (MNP); Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (CSM); Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA (CSM); Department of Dermatology, Warren Alpert Medical School of Brown University, Province, RI (EC)
| | - Seungyoun Jung
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (KI, RN, MY, PL, ZRQ, SAK, KM, YS, YI, CSF, SO); Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD (KI, CCH); Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan (KI); Department of Nutrition (MS, RN, EG, KW), Department of Epidemiology (MS, EG, SO), and Department of Biostatistics (RN), Harvard T. H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine (SJ, XZ, EG, CSF, EC, ATC) and Department of Pathology (SO), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA (PL, ATC); Department of Oncology, McGill University, Montreal, Quebec, Canada (MNP); Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (CSM); Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA (CSM); Department of Dermatology, Warren Alpert Medical School of Brown University, Province, RI (EC)
| | - Reiko Nishihara
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (KI, RN, MY, PL, ZRQ, SAK, KM, YS, YI, CSF, SO); Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD (KI, CCH); Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan (KI); Department of Nutrition (MS, RN, EG, KW), Department of Epidemiology (MS, EG, SO), and Department of Biostatistics (RN), Harvard T. H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine (SJ, XZ, EG, CSF, EC, ATC) and Department of Pathology (SO), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA (PL, ATC); Department of Oncology, McGill University, Montreal, Quebec, Canada (MNP); Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (CSM); Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA (CSM); Department of Dermatology, Warren Alpert Medical School of Brown University, Province, RI (EC)
| | - Mai Yamauchi
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (KI, RN, MY, PL, ZRQ, SAK, KM, YS, YI, CSF, SO); Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD (KI, CCH); Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan (KI); Department of Nutrition (MS, RN, EG, KW), Department of Epidemiology (MS, EG, SO), and Department of Biostatistics (RN), Harvard T. H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine (SJ, XZ, EG, CSF, EC, ATC) and Department of Pathology (SO), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA (PL, ATC); Department of Oncology, McGill University, Montreal, Quebec, Canada (MNP); Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (CSM); Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA (CSM); Department of Dermatology, Warren Alpert Medical School of Brown University, Province, RI (EC)
| | - Paul Lochhead
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (KI, RN, MY, PL, ZRQ, SAK, KM, YS, YI, CSF, SO); Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD (KI, CCH); Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan (KI); Department of Nutrition (MS, RN, EG, KW), Department of Epidemiology (MS, EG, SO), and Department of Biostatistics (RN), Harvard T. H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine (SJ, XZ, EG, CSF, EC, ATC) and Department of Pathology (SO), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA (PL, ATC); Department of Oncology, McGill University, Montreal, Quebec, Canada (MNP); Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (CSM); Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA (CSM); Department of Dermatology, Warren Alpert Medical School of Brown University, Province, RI (EC)
| | - Zhi Rong Qian
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (KI, RN, MY, PL, ZRQ, SAK, KM, YS, YI, CSF, SO); Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD (KI, CCH); Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan (KI); Department of Nutrition (MS, RN, EG, KW), Department of Epidemiology (MS, EG, SO), and Department of Biostatistics (RN), Harvard T. H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine (SJ, XZ, EG, CSF, EC, ATC) and Department of Pathology (SO), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA (PL, ATC); Department of Oncology, McGill University, Montreal, Quebec, Canada (MNP); Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (CSM); Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA (CSM); Department of Dermatology, Warren Alpert Medical School of Brown University, Province, RI (EC)
| | - Sun A Kim
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (KI, RN, MY, PL, ZRQ, SAK, KM, YS, YI, CSF, SO); Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD (KI, CCH); Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan (KI); Department of Nutrition (MS, RN, EG, KW), Department of Epidemiology (MS, EG, SO), and Department of Biostatistics (RN), Harvard T. H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine (SJ, XZ, EG, CSF, EC, ATC) and Department of Pathology (SO), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA (PL, ATC); Department of Oncology, McGill University, Montreal, Quebec, Canada (MNP); Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (CSM); Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA (CSM); Department of Dermatology, Warren Alpert Medical School of Brown University, Province, RI (EC)
| | - Kosuke Mima
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (KI, RN, MY, PL, ZRQ, SAK, KM, YS, YI, CSF, SO); Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD (KI, CCH); Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan (KI); Department of Nutrition (MS, RN, EG, KW), Department of Epidemiology (MS, EG, SO), and Department of Biostatistics (RN), Harvard T. H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine (SJ, XZ, EG, CSF, EC, ATC) and Department of Pathology (SO), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA (PL, ATC); Department of Oncology, McGill University, Montreal, Quebec, Canada (MNP); Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (CSM); Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA (CSM); Department of Dermatology, Warren Alpert Medical School of Brown University, Province, RI (EC)
| | - Yasutaka Sukawa
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (KI, RN, MY, PL, ZRQ, SAK, KM, YS, YI, CSF, SO); Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD (KI, CCH); Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan (KI); Department of Nutrition (MS, RN, EG, KW), Department of Epidemiology (MS, EG, SO), and Department of Biostatistics (RN), Harvard T. H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine (SJ, XZ, EG, CSF, EC, ATC) and Department of Pathology (SO), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA (PL, ATC); Department of Oncology, McGill University, Montreal, Quebec, Canada (MNP); Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (CSM); Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA (CSM); Department of Dermatology, Warren Alpert Medical School of Brown University, Province, RI (EC)
| | - Atsuhiro Masuda
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (KI, RN, MY, PL, ZRQ, SAK, KM, YS, YI, CSF, SO); Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD (KI, CCH); Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan (KI); Department of Nutrition (MS, RN, EG, KW), Department of Epidemiology (MS, EG, SO), and Department of Biostatistics (RN), Harvard T. H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine (SJ, XZ, EG, CSF, EC, ATC) and Department of Pathology (SO), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA (PL, ATC); Department of Oncology, McGill University, Montreal, Quebec, Canada (MNP); Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (CSM); Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA (CSM); Department of Dermatology, Warren Alpert Medical School of Brown University, Province, RI (EC)
| | - Yu Imamura
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (KI, RN, MY, PL, ZRQ, SAK, KM, YS, YI, CSF, SO); Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD (KI, CCH); Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan (KI); Department of Nutrition (MS, RN, EG, KW), Department of Epidemiology (MS, EG, SO), and Department of Biostatistics (RN), Harvard T. H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine (SJ, XZ, EG, CSF, EC, ATC) and Department of Pathology (SO), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA (PL, ATC); Department of Oncology, McGill University, Montreal, Quebec, Canada (MNP); Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (CSM); Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA (CSM); Department of Dermatology, Warren Alpert Medical School of Brown University, Province, RI (EC)
| | - Xuehong Zhang
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (KI, RN, MY, PL, ZRQ, SAK, KM, YS, YI, CSF, SO); Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD (KI, CCH); Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan (KI); Department of Nutrition (MS, RN, EG, KW), Department of Epidemiology (MS, EG, SO), and Department of Biostatistics (RN), Harvard T. H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine (SJ, XZ, EG, CSF, EC, ATC) and Department of Pathology (SO), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA (PL, ATC); Department of Oncology, McGill University, Montreal, Quebec, Canada (MNP); Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (CSM); Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA (CSM); Department of Dermatology, Warren Alpert Medical School of Brown University, Province, RI (EC)
| | - Michael N Pollak
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (KI, RN, MY, PL, ZRQ, SAK, KM, YS, YI, CSF, SO); Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD (KI, CCH); Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan (KI); Department of Nutrition (MS, RN, EG, KW), Department of Epidemiology (MS, EG, SO), and Department of Biostatistics (RN), Harvard T. H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine (SJ, XZ, EG, CSF, EC, ATC) and Department of Pathology (SO), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA (PL, ATC); Department of Oncology, McGill University, Montreal, Quebec, Canada (MNP); Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (CSM); Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA (CSM); Department of Dermatology, Warren Alpert Medical School of Brown University, Province, RI (EC)
| | - Christos S Mantzoros
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (KI, RN, MY, PL, ZRQ, SAK, KM, YS, YI, CSF, SO); Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD (KI, CCH); Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan (KI); Department of Nutrition (MS, RN, EG, KW), Department of Epidemiology (MS, EG, SO), and Department of Biostatistics (RN), Harvard T. H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine (SJ, XZ, EG, CSF, EC, ATC) and Department of Pathology (SO), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA (PL, ATC); Department of Oncology, McGill University, Montreal, Quebec, Canada (MNP); Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (CSM); Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA (CSM); Department of Dermatology, Warren Alpert Medical School of Brown University, Province, RI (EC)
| | - Curtis C Harris
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (KI, RN, MY, PL, ZRQ, SAK, KM, YS, YI, CSF, SO); Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD (KI, CCH); Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan (KI); Department of Nutrition (MS, RN, EG, KW), Department of Epidemiology (MS, EG, SO), and Department of Biostatistics (RN), Harvard T. H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine (SJ, XZ, EG, CSF, EC, ATC) and Department of Pathology (SO), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA (PL, ATC); Department of Oncology, McGill University, Montreal, Quebec, Canada (MNP); Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (CSM); Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA (CSM); Department of Dermatology, Warren Alpert Medical School of Brown University, Province, RI (EC)
| | - Edward Giovannucci
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (KI, RN, MY, PL, ZRQ, SAK, KM, YS, YI, CSF, SO); Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD (KI, CCH); Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan (KI); Department of Nutrition (MS, RN, EG, KW), Department of Epidemiology (MS, EG, SO), and Department of Biostatistics (RN), Harvard T. H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine (SJ, XZ, EG, CSF, EC, ATC) and Department of Pathology (SO), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA (PL, ATC); Department of Oncology, McGill University, Montreal, Quebec, Canada (MNP); Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (CSM); Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA (CSM); Department of Dermatology, Warren Alpert Medical School of Brown University, Province, RI (EC)
| | - Charles S Fuchs
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (KI, RN, MY, PL, ZRQ, SAK, KM, YS, YI, CSF, SO); Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD (KI, CCH); Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan (KI); Department of Nutrition (MS, RN, EG, KW), Department of Epidemiology (MS, EG, SO), and Department of Biostatistics (RN), Harvard T. H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine (SJ, XZ, EG, CSF, EC, ATC) and Department of Pathology (SO), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA (PL, ATC); Department of Oncology, McGill University, Montreal, Quebec, Canada (MNP); Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (CSM); Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA (CSM); Department of Dermatology, Warren Alpert Medical School of Brown University, Province, RI (EC)
| | - Eunyoung Cho
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (KI, RN, MY, PL, ZRQ, SAK, KM, YS, YI, CSF, SO); Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD (KI, CCH); Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan (KI); Department of Nutrition (MS, RN, EG, KW), Department of Epidemiology (MS, EG, SO), and Department of Biostatistics (RN), Harvard T. H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine (SJ, XZ, EG, CSF, EC, ATC) and Department of Pathology (SO), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA (PL, ATC); Department of Oncology, McGill University, Montreal, Quebec, Canada (MNP); Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (CSM); Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA (CSM); Department of Dermatology, Warren Alpert Medical School of Brown University, Province, RI (EC)
| | - Andrew T Chan
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (KI, RN, MY, PL, ZRQ, SAK, KM, YS, YI, CSF, SO); Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD (KI, CCH); Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan (KI); Department of Nutrition (MS, RN, EG, KW), Department of Epidemiology (MS, EG, SO), and Department of Biostatistics (RN), Harvard T. H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine (SJ, XZ, EG, CSF, EC, ATC) and Department of Pathology (SO), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA (PL, ATC); Department of Oncology, McGill University, Montreal, Quebec, Canada (MNP); Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (CSM); Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA (CSM); Department of Dermatology, Warren Alpert Medical School of Brown University, Province, RI (EC)
| | - Kana Wu
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (KI, RN, MY, PL, ZRQ, SAK, KM, YS, YI, CSF, SO); Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD (KI, CCH); Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan (KI); Department of Nutrition (MS, RN, EG, KW), Department of Epidemiology (MS, EG, SO), and Department of Biostatistics (RN), Harvard T. H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine (SJ, XZ, EG, CSF, EC, ATC) and Department of Pathology (SO), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA (PL, ATC); Department of Oncology, McGill University, Montreal, Quebec, Canada (MNP); Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (CSM); Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA (CSM); Department of Dermatology, Warren Alpert Medical School of Brown University, Province, RI (EC)
| | - Shuji Ogino
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (KI, RN, MY, PL, ZRQ, SAK, KM, YS, YI, CSF, SO); Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD (KI, CCH); Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan (KI); Department of Nutrition (MS, RN, EG, KW), Department of Epidemiology (MS, EG, SO), and Department of Biostatistics (RN), Harvard T. H. Chan School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine (SJ, XZ, EG, CSF, EC, ATC) and Department of Pathology (SO), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA (PL, ATC); Department of Oncology, McGill University, Montreal, Quebec, Canada (MNP); Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (CSM); Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA (CSM); Department of Dermatology, Warren Alpert Medical School of Brown University, Province, RI (EC)
| |
Collapse
|
|
38
|
DeClercq V, McMurray DN, Chapkin RS. Obesity promotes colonic stem cell expansion during cancer initiation. Cancer Lett 2015; 369:336-43. [PMID: 26455770 DOI: 10.1016/j.canlet.2015.10.001] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Revised: 09/29/2015] [Accepted: 10/01/2015] [Indexed: 02/08/2023]
Abstract
There is an urgent need to elucidate the mechanistic links between obesity and colon cancer. Convincing evidence for the role of Lgr5(+) stem cells in colon tumorigenesis has been established; however, the influence of obesity on stem cell maintenance is unknown. We assessed the effects of high fat (HF) feeding on colonic stem cell maintenance during cancer initiation (AOM induced) and the responsiveness of stem cells to adipokine signaling pathways. The number of colonic GFP(+) stem cells was significantly higher in the AOM-injected HF group compared to the LF group. The Lgr5(+) stem cells of the HF fed mice exhibited statistically significant increases in cell proliferation and decreases in apoptosis in response to AOM injection compared to the LF group. Colonic organoid cultures from lean mice treated with an adiponectin receptor agonist exhibited a reduction in Lgr5-GPF(+) stem cell number and an increase in apoptosis; however, this response was diminished in the organoid cultures from obese mice. These results suggest that the responsiveness of colonic stem cells to adiponectin in diet-induced obesity is impaired and may contribute to the stem cell accumulation observed in obesity.
Collapse
Affiliation(s)
- V DeClercq
- Program in Integrative Nutrition and Complex Diseases, Texas A&M University, College Station, TX, USA
| | - D N McMurray
- Program in Integrative Nutrition and Complex Diseases, Texas A&M University, College Station, TX, USA; Department of Microbial Pathogenesis and Immunology, School of Medicine, Texas A&M University Health Science Center, College Station, TX, USA
| | - R S Chapkin
- Program in Integrative Nutrition and Complex Diseases, Texas A&M University, College Station, TX, USA; Department of Microbial Pathogenesis and Immunology, School of Medicine, Texas A&M University Health Science Center, College Station, TX, USA; Department of Nutrition and Food Science, Texas A&M University, College Station, MS 2253, Cater Mattil, TX 77843-2253, USA; Center for Translational Environmental Health Research, Texas A&M University, College Station, TX, USA.
| |
Collapse
|
|
39
|
Nimptsch K, Aleksandrova K, Boeing H, Janke J, Lee YA, Jenab M, Kong SY, Tsilidis KK, Weiderpass E, Bueno-De-Mesquita HBA, Siersema PD, Jansen EHJM, Trichopoulou A, Tjønneland A, Olsen A, Wu C, Overvad K, Boutron-Ruault MC, Racine A, Freisling H, Katzke V, Kaaks R, Lagiou P, Trichopoulos D, Severi G, Naccarati A, Mattiello A, Palli D, Grioni S, Tumino R, Peeters PH, Ljuslinder I, Nyström H, Brändstedt J, Sánchez MJ, Gurrea AB, Bonet CB, Chirlaque MD, Dorronsoro M, Quirós JR, Travis RC, Khaw KT, Wareham N, Riboli E, Gunter MJ, Pischon T. Plasma fetuin-A concentration, genetic variation in the AHSG gene and risk of colorectal cancer. Int J Cancer 2015; 137:911-20. [PMID: 25611809 DOI: 10.1002/ijc.29448] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Accepted: 11/27/2014] [Indexed: 12/30/2022]
Abstract
Fetuin-A, also referred to as α2-Heremans-Schmid glycoprotein (AHSG), is a liver protein known to inhibit insulin actions. Hyperinsulinemia is a possible risk factor for colorectal cancer; however, the role of fetuin-A in the development of colorectal cancer is unclear. We investigated the association between circulating fetuin-A and colorectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Fetuin-A concentrations were measured in prediagnostic plasma samples from 1,367 colorectal cancer cases and 1,367 matched controls. In conditional logistic regression models adjusted for potential confounders, the estimated relative risk (95% confidence interval) of colorectal cancer per 40 µg/mL higher fetuin-A concentrations (approximately one standard deviation) was 1.13 (1.02-1.24) overall, 1.21 (1.05-1.39) in men, 1.06 (0.93-1.22) in women, 1.13 (1.00-1.27) for colon cancer and 1.12 (0.94-1.32) for rectal cancer. To improve causal inference in a Mendelian Randomization approach, five tagging single nucleotide polymorphisms of the AHSG gene were genotyped in a subset of 456 case-control pairs. The AHSG allele-score explained 21% of the interindividual variation in plasma fetuin-A concentrations. In instrumental variable analysis, genetically raised fetuin-A was not associated with colorectal cancer risk (relative risk per 40 µg/mL genetically determined higher fetuin-A was 0.98, 95% confidence interval: 0.73-1.33). The findings of our study indicate a modest linear association between fetuin-A concentrations and risk of colorectal cancer but suggest that fetuin-A may not be causally related to colorectal cancer development.
Collapse
Affiliation(s)
- Katharina Nimptsch
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany
- Department of Nutrition, Harvard School of Public Health, Boston, MA
| | - Krasimira Aleksandrova
- Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbruecke, Nuthetal, Germany
| | - Heiner Boeing
- Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbruecke, Nuthetal, Germany
| | - Jürgen Janke
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany
| | - Young-Ae Lee
- Genetics of Allergic Disease Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany
| | - Mazda Jenab
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - So Yeon Kong
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Konstantinos K Tsilidis
- Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | - Elisabete Weiderpass
- Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
- Department of Research, Cancer Registry of Norway, Oslo, Norway
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Samfundet Folkhälsan, Helsinki, Finland
| | - H B As Bueno-De-Mesquita
- National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
- Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands
- Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, United Kingdom
| | - Peter D Siersema
- Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands
| | - Eugène H J M Jansen
- Center for Health Protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
| | - Antonia Trichopoulou
- Hellenic Health Foundation, Athens, Greece
- Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece
| | | | - Anja Olsen
- Danish Cancer Society Research Center, Copenhagen, Denmark
| | - Chunsen Wu
- Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
| | - Kim Overvad
- Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
| | - Marie-Christine Boutron-Ruault
- INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health team, Villejuif, France
- Université Paris Sud, UMRS, 1018, Villejuif, France
- Institut Gustave Roussy (IGR), Villejuif, France
| | - Antoine Racine
- INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health team, Villejuif, France
- Université Paris Sud, UMRS, 1018, Villejuif, France
- Institut Gustave Roussy (IGR), Villejuif, France
| | - Heinz Freisling
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Verena Katzke
- Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
| | - Rudolf Kaaks
- Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
| | - Pagona Lagiou
- Hellenic Health Foundation, Athens, Greece
- Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece
- Department of Epidemiology, Harvard School of Public Health, Boston, MA
| | - Dimitrios Trichopoulos
- Hellenic Health Foundation, Athens, Greece
- Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece
- Department of Epidemiology, Harvard School of Public Health, Boston, MA
| | | | | | - Amalia Mattiello
- Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
| | - Domenico Palli
- Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy
| | - Sara Grioni
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Rosario Tumino
- Cancer Registry and Histopathology Unit, "Civic - M.P. Arezzo" Hospital, ASP Ragusa, Italy
| | - Petra H Peeters
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands
| | - Ingrid Ljuslinder
- Department of Radio Sciences, Oncology, Umeå University, Umea, Sweden
| | - Hanna Nyström
- Department of Surgery, Department of Surgical and Perioperative Sciences, Umeå University, Sweden
| | - Jenny Brändstedt
- Department of Clinical Sciences, Lund Oncology and Pathology, Lund University, Skåne University Hospital, Lund, Sweden
| | - María-José Sánchez
- Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Granada, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER de Epidemiologia y Salud Publica-CIBERESP), Spain
| | - Aurelio Barricarte Gurrea
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER de Epidemiologia y Salud Publica-CIBERESP), Spain
- Navarre Public Health Institute, Pamplona, Spain
| | - Catalina Bonet Bonet
- Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Barcelona, Spain
| | - María-Dolores Chirlaque
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBER de Epidemiologia y Salud Publica-CIBERESP), Spain
- Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain
| | - Miren Dorronsoro
- Public Health Direction and Biodonostia-Ciberesp, Basque Regional Health Department, San Sebastian, Spain
| | | | - Ruth C Travis
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
| | - Kay-Tee Khaw
- Clinical Gerontology, Department of Public Health and Primary care, School of Clinical Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
| | - Nick Wareham
- Medical Research Council, Epidemiology Unit, University of Cambridge, United Kingdom
| | - Elio Riboli
- Division of Epidemiology, Public Health and Primary Care, Imperial College, London, United Kingdom
| | - Marc J Gunter
- Division of Epidemiology, Public Health and Primary Care, Imperial College, London, United Kingdom
| | - Tobias Pischon
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany
| |
Collapse
|
|
40
|
Schlesinger S, Lieb W, Koch M, Fedirko V, Dahm CC, Pischon T, Nöthlings U, Boeing H, Aleksandrova K. Body weight gain and risk of colorectal cancer: a systematic review and meta-analysis of observational studies. Obes Rev 2015; 16:607-19. [PMID: 25925734 DOI: 10.1111/obr.12286] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2015] [Revised: 04/01/2015] [Accepted: 04/01/2015] [Indexed: 12/21/2022]
Abstract
While the relationship between body mass index as an indicator of excess body weight and the risk of colorectal cancer (CRC) is well established, the association between body weight gain in adulthood and risk of CRC remains unresolved. We quantified this association in a meta-analysis of 12 observational studies published until November 2014 with a total of 16,151 incident CRC cases. Random effect models were used to obtain summary relative risks (RR) and 95% confidence intervals (95% CIs). Between-study heterogeneity was assessed using I(2) statistics. Overall, the summary RR (95% CI) was 1.22 (1.14-1.30) for high body weight gain (midpoint: 15.2 kg) compared with stable weight (P for heterogeneity = 0.182; I(2) = 21.2%). In a dose-response analysis, each 5 kg weight gain was associated with a 4% (95% CI: 2%-5%) higher risk of CRC. The association persisted after adjustment for body weight at younger age and was present for both men and women, as well as for colon and rectal cancer. Differences by sex were detected for colon cancer (P for interaction = 0.003, with higher risk for men than women), but not for rectal cancer (P for interaction = 0.613). In conclusion, these data underscore the importance of body weight management from early adulthood onwards for the prevention of CRC development.
Collapse
Affiliation(s)
- S Schlesinger
- Institute of Epidemiology, Christian-Albrechts University of Kiel, Kiel, Germany
| | - W Lieb
- Institute of Epidemiology, Christian-Albrechts University of Kiel, Kiel, Germany
| | - M Koch
- Institute of Epidemiology, Christian-Albrechts University of Kiel, Kiel, Germany
| | - V Fedirko
- Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - C C Dahm
- Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
| | - T Pischon
- Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany
| | - U Nöthlings
- Department of Nutrition and Food Sciences, Nutritional Epidemiology, University of Bonn, Bonn, Germany
| | - H Boeing
- Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| | - K Aleksandrova
- Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| |
Collapse
|
|
41
|
Song M, Gong J, Giovannucci EL, Berndt SI, Brenner H, Chang-Claude J, Curtis KR, Harrison TA, Hoffmeister M, Hsu L, Jiao S, Le Marchand L, Potter JD, Schoen RE, Seminara D, Slattery ML, White E, Wu K, Ogino S, Fuchs CS, Hunter DJ, Tworoger SS, Hu FB, Rimm E, Jensen M, Peters U, Chan AT. Genetic variants of adiponectin and risk of colorectal cancer. Int J Cancer 2015; 137:154-64. [PMID: 25431318 PMCID: PMC4405454 DOI: 10.1002/ijc.29360] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2014] [Accepted: 11/05/2014] [Indexed: 01/18/2023]
Abstract
Circulating adiponectin has been associated with lower risk of colorectal cancer (CRC). Genome-wide association studies have identified several single-nucleotide polymorphisms (SNPs) associated with adiponectin levels. However, it is unclear whether these SNPs are associated with CRC risk. In addition, previous data on SNPs in the adiponectin pathway and their associations with CRC are inconsistent. Therefore, we examined 19 SNPs in genes related to adiponectin or its receptors and their associations with CRC using logistic regression among 7,020 cases and 7,631 controls drawn from ten studies included in the Genetics and Epidemiology of Colorectal Cancer Consortium. Using data from a subset of two large cohort studies, we also assessed the contribution of individual SNPs and an adiponectin genetic score to plasma adiponectin after accounting for lifestyle factors among 2,217 women and 619 men. We did not find any statistically significant association between the 19 adiponectin-associated SNPs and CRC risk (multivariable-adjusted odds ratios ranged from 0.89 to 1.05, all p > 0.05). Each SNP explained less than 2.50% of the variance of plasma adiponectin, and the genetic score collectively accounted for 2.95 and 1.42% of the variability of adiponectin in women and men, respectively, after adjustment for age, body mass index, physical activity, smoking, alcohol consumption, regular use of aspirin or nonsteroidal anti-inflammatory drug and postmenopausal hormone use. In conclusion, our findings do not support an association between known adiponectin-related common SNPs and CRC incidence. However, known common SNPs account for only a limited proportion of the interindividual variance in circulating adiponectin. Further work is warranted to investigate the relationship between adiponectin and CRC while accounting for other components in the pathway.
Collapse
Affiliation(s)
- Mingyang Song
- Department of Nutrition, Harvard School of Public Health, Boston, MA
- Department of Epidemiology, Harvard School of Public Health, Boston, MA
| | - Jian Gong
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Edward L. Giovannucci
- Department of Nutrition, Harvard School of Public Health, Boston, MA
- Department of Epidemiology, Harvard School of Public Health, Boston, MA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
| | - Sonja I. Berndt
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Jenny Chang-Claude
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Keith R. Curtis
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Tabitha A. Harrison
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Li Hsu
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
- Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA
| | - Shuo Jiao
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
| | | | - John D. Potter
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
- Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA
- Centre for Public Health Research, Massey University, Wellington, New Zealand
| | - Robert E. Schoen
- Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Daniela Seminara
- Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Martha L. Slattery
- Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT
| | - Emily White
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
- Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA
| | - Kana Wu
- Department of Nutrition, Harvard School of Public Health, Boston, MA
| | - Shuji Ogino
- Department of Epidemiology, Harvard School of Public Health, Boston, MA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
| | - Charles S. Fuchs
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
| | - David J. Hunter
- Department of Nutrition, Harvard School of Public Health, Boston, MA
- Department of Epidemiology, Harvard School of Public Health, Boston, MA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
| | - Shelley S. Tworoger
- Department of Epidemiology, Harvard School of Public Health, Boston, MA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
| | - Frank B. Hu
- Department of Nutrition, Harvard School of Public Health, Boston, MA
- Department of Epidemiology, Harvard School of Public Health, Boston, MA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
| | - Eric Rimm
- Department of Nutrition, Harvard School of Public Health, Boston, MA
- Department of Epidemiology, Harvard School of Public Health, Boston, MA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
| | - Majken Jensen
- Department of Nutrition, Harvard School of Public Health, Boston, MA
| | - Ulrike Peters
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
- Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA
| | - Andrew T. Chan
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| |
Collapse
|
|
42
|
Norris L, Malkar A, Horner-Glister E, Hakimi A, Ng LL, Gescher AJ, Creaser C, Sale S, Jones DJL. Search for novel circulating cancer chemopreventive biomarkers of dietary rice bran intervention in ApcMin
mice model of colorectal carcinogenesis, using proteomic and metabolic profiling strategies. Mol Nutr Food Res 2015; 59:1827-36. [DOI: 10.1002/mnfr.201400818] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2014] [Revised: 04/30/2015] [Accepted: 05/05/2015] [Indexed: 12/19/2022]
Affiliation(s)
- Leonie Norris
- Department of Cancer Studies and Molecular Medicine; Leicester Royal Infirmary; University of Leicester; Leicester UK
| | - Aditya Malkar
- Centre for Analytical Science; Department of Chemistry; Loughborough University; Loughborough Leicestershire UK
| | - Emma Horner-Glister
- Department of Cancer Studies and Molecular Medicine; Leicester Royal Infirmary; University of Leicester; Leicester UK
| | - Amirmansoor Hakimi
- Department of Cancer Studies and Molecular Medicine; Leicester Royal Infirmary; University of Leicester; Leicester UK
| | - Leong L. Ng
- Department of Cardiovascular Sciences, NIHR Leicester Cardiovascular Biomedical Research Unit; Glenfield Hospital; Leicester UK
| | - Andreas J. Gescher
- Department of Cancer Studies and Molecular Medicine; Leicester Royal Infirmary; University of Leicester; Leicester UK
| | - Colin Creaser
- Department of Cancer Studies and Molecular Medicine; Leicester Royal Infirmary; University of Leicester; Leicester UK
| | - Stewart Sale
- Department of Cancer Studies and Molecular Medicine; Leicester Royal Infirmary; University of Leicester; Leicester UK
| | - Donald J. L. Jones
- Department of Cancer Studies and Molecular Medicine; Leicester Royal Infirmary; University of Leicester; Leicester UK
- Department of Cardiovascular Sciences, NIHR Leicester Cardiovascular Biomedical Research Unit; Glenfield Hospital; Leicester UK
| |
Collapse
|
|
43
|
Young MRI, Levingston C, Johnson SD. Cytokine and Adipokine Levels in Patients with Premalignant Oral Lesions or in Patients with Oral Cancer Who Did or Did Not Receive 1α,25-Dihydroxyvitamin D3 Treatment upon Cancer Diagnosis. Cancers (Basel) 2015; 7:1109-24. [PMID: 26120967 PMCID: PMC4586760 DOI: 10.3390/cancers7030827] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2015] [Revised: 06/09/2015] [Accepted: 06/17/2015] [Indexed: 12/17/2022] Open
Abstract
Differences in levels of inflammation-modulating cytokines and adipokines in patients with premalignant oral lesions versus in patients that develop squamous cell carcinoma of the head and neck (HNSCC) were assessed. Also assessed was the impact of treating HNSCC patients with the immune regulatory mediator, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], on modulators of inflammation. Compared to healthy controls, patients with premalignant oral lesions had increases in their systemic levels of the inflammatory cytokines IL-6 and IL-17, and increases in the adipokine, leptin. However, levels of these pro-inflammatory cytokines and adipokine were reduced in patients with HNSCC. Treatment of HNSCC patients with 1,25(OH)2D3 increased levels of each of the measured immune mediators. Levels of the anti-inflammatory adipokine, adiponectin, were shifted inversely with the levels of the pro-inflammatory cytokines and with leptin. These studies demonstrate heightened immune reactivity in patients with premalignant lesions, which wanes in patients with HNSCC, but which is restored by treatment with 1,25(OH)2D3.
Collapse
Affiliation(s)
- M Rita I Young
- Medical Research Service (151), Ralph H. Johnson Veterans Affairs Medical Center, 109 Bee Street, Charleston, SC 29401, USA.
- Department of Otolaryngology, Head and Neck Surgery, Medical University of South Carolina, 135 Rutledge Avenue, Charleston, SC 29425, USA.
| | - Corinne Levingston
- Medical Research Service (151), Ralph H. Johnson Veterans Affairs Medical Center, 109 Bee Street, Charleston, SC 29401, USA.
| | - Sara D Johnson
- Department of Otolaryngology, Head and Neck Surgery, Medical University of South Carolina, 135 Rutledge Avenue, Charleston, SC 29425, USA.
| |
Collapse
|
|
44
|
Katira A, Tan PH. Adiponectin and its receptor signaling: an anti-cancer therapeutic target and its implications for anti-tumor immunity. Expert Opin Ther Targets 2015; 19:1105-25. [DOI: 10.1517/14728222.2015.1035710] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
|
|
45
|
Chandler PD, Buring JE, Manson JE, Moorthy MV, Zhang S, Lee IM, Lin JH. Association between plasma adiponectin levels and colorectal cancer risk in women. Cancer Causes Control 2015; 26:1047-52. [PMID: 25941065 DOI: 10.1007/s10552-015-0590-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2015] [Accepted: 04/21/2015] [Indexed: 01/02/2023]
Abstract
BACKGROUND Adiponectin, an adipocyte-secreted hormone, has insulin-sensitizing characteristics. It remains unclear whether adiponectin may influence colorectal cancer development. METHODS To determine whether prediagnostic levels of adiponectin were associated with risk of incident colorectal cancer in the Women's Health Study, we conducted a nested case-control study of 275 colorectal cancer cases and 275 matched controls. Each case was matched to a control by age, ethnicity, fasting status at the time of blood collection, time of day when blood was drawn, and month of blood draw. Multivariable logistic regression with adjustment for colorectal cancer risk factors was used to estimate the odds ratio (OR) and 95 % confidence interval (CI) for risk of colorectal cancer incidence and mortality by adiponectin quartiles based on the control distribution. RESULTS Median plasma adiponectin level was similar in cases versus controls (6.00 vs. 6.24 μg/mL). In multivariable-adjusted logistic regression models, high plasma adiponectin levels were not significantly associated with risk of colorectal cancer [quartile 4 (Q4) vs. quartile 1 (Q1): OR (95 % CI) 0.86 (0.48-1.56), p trend = 0.63]. CONCLUSIONS These results suggest no appreciable association between plasma adiponectin and risk of colorectal cancer in women. Confirmation of these observations in larger studies is needed.
Collapse
Affiliation(s)
- Paulette D Chandler
- Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Avenue, 3rd Floor, Boston, MA, 02215, USA,
| | | | | | | | | | | | | |
Collapse
|
|
46
|
Association of adulthood weight gain with circulating adipokine and insulin resistance in the Japanese population. Eur J Clin Nutr 2014; 69:462-6. [DOI: 10.1038/ejcn.2014.257] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2014] [Revised: 10/12/2014] [Accepted: 10/29/2014] [Indexed: 02/07/2023]
|
|
47
|
Joshi RK, Lee SA. Obesity related adipokines and colorectal cancer: a review and meta-analysis. Asian Pac J Cancer Prev 2014; 15:397-405. [PMID: 24528064 DOI: 10.7314/apjcp.2014.15.1.397] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Obesity has been considered as an important risk factor for the development of colorectal cancer (CRC), but the association has not been fully elucidated. Obesity is linked significantly to adipose tissue dysfunction and to alteration of adipokines in blood; in particular, obesity-induced inflammation is thought to be an important link between obesity and colorectal cancer. Based on epidemiological studies, we undertook a systematic review to understand the association of circulating levels of selected adipokines, including adiponectin, leptin, resistin, IL-6 and TNF-α, with the level of CRC risk. Most prospective studies suggested protective effects of adiponectin, but these were attenuated by body mass index (BMI) and waist circumference (WC) data in our meta-analysis. On the other hand, meta-analyses for leptin and CRC did not demonstrate any association, similar to the results of systematic review. Although it proved difficult to determine whether other selected adipokines (resistin, IL-6 and TNF-α) were related to CRC risk due to small number of reports, the present systematic review suggested a positive association with elevated resistin levels but null associations with IL-6 and TNF-α.
Collapse
Affiliation(s)
- Rakhi Kumari Joshi
- Department of Preventive Medicine, Kangwon National University School of Medicine, Chuncheon-si, Gangwon-do, South Korea E-mail :
| | | |
Collapse
|
|
48
|
Muc-Wierzgoń M, Nowakowska-Zajdel E, Dzięgielewska-Gęsiak S, Kokot T, Klakla K, Fatyga E, Grochowska-Niedworok E, Waniczek D, Wierzgoń J. Specific metabolic biomarkers as risk and prognostic factors in colorectal cancer. World J Gastroenterol 2014; 20:9759-9774. [PMID: 25110413 PMCID: PMC4123364 DOI: 10.3748/wjg.v20.i29.9759] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Revised: 11/05/2013] [Accepted: 04/23/2014] [Indexed: 02/06/2023] Open
Abstract
Advances in genomics, molecular pathology and metabolism have generated many candidate biomarkers of colorectal cancer with potential clinical value. Epidemiological and biological studies suggest a role for adiposity, dyslipidaemia, hyperinsulinemia, altered glucose homeostasis, and elevated expression of insulin-like growth factor (IGF) axis members in the risk and prognosis of cancer. This review discusses some recent past and current approaches being taken by researches in obesity and metabolic disorders. The authors describe three main systems as the most studied metabolic candidates of carcinogenesis: dyslipidemias, adipokines and insulin/IGF axis. However, each of these components is unsuccessful in defining the diseases risk and progression, while their co-occurrence increases cancer incidence and mortality in both men and women.
Collapse
|
|
49
|
Tilg H, Moschen AR. Mechanisms behind the link between obesity and gastrointestinal cancers. Best Pract Res Clin Gastroenterol 2014; 28:599-610. [PMID: 25194178 DOI: 10.1016/j.bpg.2014.07.006] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2014] [Revised: 06/27/2014] [Accepted: 07/05/2014] [Indexed: 01/31/2023]
Abstract
Obesity and obesity-related disorders such as non-alcoholic fatty liver disease (NAFLD), metabolic syndrome and type 2 diabetes exhibit an increased risk of developing various gastrointestinal cancers. These malignancies include mainly esophageal, gastric, colorectal, pancreatic and hepatocellular carcinoma. Whereas underlying pathomechanisms remain unclear, chronic inflammation accompanying obesity has evolved in the last years as a crucial contributing factor. Obesity is also commonly characterized by inflammation in the organ where those cancers appear. Various pathways might participate involving rather diverse components such as innate immunity, (adipo)-cytokines such as adiponectin or leptin, insulin, insulin-like growth factors, the gut's microbiota and others. An imbalance in these systems could substantially contribute to chronic inflammation and subsequent cancer development. Future studies have to elucidate in more detail underlying mechanisms in the development of obesity-related carcinogensis and potential therapeutic strategies besides weight loss.
Collapse
Affiliation(s)
- Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Endocrinology & Metabolism, Medical University Innsbruck, Austria.
| | - Alexander R Moschen
- Department of Internal Medicine I, Gastroenterology, Endocrinology & Metabolism, Medical University Innsbruck, Austria
| |
Collapse
|
|
50
|
Joshi RK, Kim WJ, Lee SA. Association between obesity-related adipokines and colorectal cancer: A case-control study and meta-analysis. World J Gastroenterol 2014; 20:7941-7949. [PMID: 24976730 PMCID: PMC4069321 DOI: 10.3748/wjg.v20.i24.7941] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2013] [Revised: 01/24/2014] [Accepted: 04/09/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To examine the association between obesity-related adipokines (adiponectin, leptin, resistin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and colorectal cancer (CRC) risk.
METHODS: Serum levels of adipokines were measured in 100 CRC patients and age- and sex-matched controls for the data analysis. Unconditional logistic regression models were used for estimating ORs and 95%CIs related to each adipokine. For the meta-analysis, studies published before July 2013 available on Medline/PubMed and EMBASE were retrieved. The analysis included a total of 17 relevant studies (including the present case-control study): nine studies on adiponectin and eight on leptin. The effect sizes of ORs and 95%CIs were estimated using RevMan 5.1. Heterogeneity was evaluated using Cochran’s Q-test and I2 statistics.
RESULTS: Among the five adipokines, only resistin levels were significantly higher in cases than in controls (P < 0.001). The case-control study results showed no association between adiponectin and CRC and a negative association between leptin and CRC. However, the results of the meta-analysis showed a significant inverse association between adiponectin and CRC (OR = 0.91, 95%CI: 0.83-1.00, P = 0.04) and no association between CRC and leptin. After stratification by study design, an inverse association between adiponectin and CRC was observed in prospective studies only (OR = 0.90, 95%CI: 0.82-0.99, P = 0.03), whereas the association between leptin and CRC was inconsistent (prospective studies: OR = 1.14, 95%CI: 1.02-1.27, P = 0.02 and retrospective studies: OR = 0.47, 95%CI: 0.29-0.74, P = 0.001). The associations of resistin and TNF-α with CRC risk were positive, but no association was observed for IL-6.
CONCLUSION: Our results suggest a negative association of leptin, positive associations of resistin and TNF-α, and null associations of adiponectin and IL-6 with CRC. However, further studies with larger number of prospective approaches are needed.
Collapse
|