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Herreros‐Pomares A, Hervás D, Bagán L, Proaño A, Bagan J. Proliferative verrucous and homogeneous Leukoplakias exhibit differential methylation patterns. Oral Dis 2025; 31:137-147. [PMID: 38852153 PMCID: PMC11808169 DOI: 10.1111/odi.15028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 03/20/2024] [Accepted: 05/20/2024] [Indexed: 06/11/2024]
Abstract
OBJECTIVE Proliferative verrucous leukoplakia (PVL) is considered a clinically distinct entity from other oral leucoplakias (OLs) due to its clinical presentation and evolution. However, molecular differences between them remain unclear. We aimed to determine whether there are methylation differences between PVL and other forms of OLs. MATERIALS AND METHODS Oral biopsies from 12 patients with PVL, eight patients with homogeneous leucoplakia (HL), and 10 healthy individuals were obtained for a genome-wide DNA methylation analysis via the Infinium EPIC Platform. RESULTS A total of 1815 differentially methylated CpGs were found between PVL and HL, with a prominent state of hypermethylation in HL patients. CpGs covered 813 genes with distinct roles, including cell adhesion, extracellular matrix organization, and cell and synaptic signaling. 43% of these genes had been previously described in cancer and associated with prognosis. We developed a multinomial logistic regression model able to differentiate HL, PVL, and control samples. The model had a cross-validated estimate of 73% and included differentially methylated cancer-related genes between the pathological conditions and the healthy donors, including ADNP, BRCA2, CDK13, GNB1, NIN, NUMB, PIK3C2B, PTK2, SHISA4, THSD7B, WWP1, and ZNF292. It also included CpGs covering differentially methylated genes in HL (MEN1 and TNRC6B) and PVL (ACOXL, ADH1B, CAMTA1, CBFA2T3, CPXM2, LRFN2, SORCS2, and SPN). CONCLUSIONS PVL and HL present differential methylation patterns that could be linked to their differential clinical behavior. Our findings show the potential of methylation markers and suggest novel diagnostic biomarkers.
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Affiliation(s)
- Alejandro Herreros‐Pomares
- Department of BiotechnologyUniversitat Politècnica de ValènciaValenciaSpain
- Centro de Investigación Biomédica en Red CáncerCIBERONCMadridSpain
| | - David Hervás
- Departament of Applied Statistics and Operational Research, and QualityUniversitat Politècnica de ValènciaValenciaSpain
| | - Leticia Bagán
- Medicina Oral Unit, Stomatology DepartmentValencia UniversityValenciaSpain
| | - Alex Proaño
- Medicina Oral Unit, Stomatology DepartmentValencia UniversityValenciaSpain
| | - José Bagan
- Centro de Investigación Biomédica en Red CáncerCIBERONCMadridSpain
- Medicina Oral Unit, Stomatology DepartmentValencia UniversityValenciaSpain
- Department of Stomatology and Maxillofacial SurgeryHospital General Universitario de ValenciaValenciaSpain
- Precancer and Oral Cancer Research Group of Valencia UniversityValenciaSpain
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Guo D, Jin J, Li D, He Y, Lin Y. Analysis of the incidence and mortality trends of esophageal cancer in cancer registry areas of China and Japan. Int J Cancer 2024; 155:1376-1386. [PMID: 38771567 DOI: 10.1002/ijc.35003] [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: 01/21/2024] [Revised: 04/17/2024] [Accepted: 04/22/2024] [Indexed: 05/22/2024]
Abstract
This study aims to analyze the prevalence trend of esophageal cancer in Japan and China to provide suggestions for the prevention and treatment of esophageal cancer. The results showed that the incidence rate for the years 2010-2018 significantly decreased with an APC of 5.66%, and the mortality rate from 2010 to 2015 had an APC of -5.87% in China. However, the incidence rate of Japanese women showed an upward trend, with an APC of 4.09% from 2010 to 2019. The mortality rate of esophageal cancer in Japan showed a downward trend, with an APC of -2.96% from 2010 to 2021. From 2010 to 2018, Chinese esophageal squamous cell carcinoma accounted for the highest proportion, accounting for 85.96%, with the largest distribution in the middle, accounting for 47.25%. Patients are mostly diagnosed at stage III, and the relative survival rate from 2012 to 2015 was 30.3%. Japan also has the highest proportion of squamous cell carcinoma, and the lesions are also mostly located in the middle segment. While Japanese esophageal cancer patients are mostly diagnosed at stage I, and the relative survival rate was 41.5% in Japan from 2009 to 2011. The results of this article indicate that the current prevalence of esophageal cancer in China and Japan is generally declining, and the quality of life of patients is gradually improving, but effective screening and prevention strategies are still needed to reduce the burden of this disease.
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Affiliation(s)
- Dongli Guo
- Cancer Institute, Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Jing Jin
- Cancer Institute, Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Daojuan Li
- Cancer Institute, Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yutong He
- Cancer Institute, Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yingsong Lin
- Department of Public Health, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
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3
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Liu Q, Li S, Mao M, Gui X, Zhang Y, Zhao Y, Yu L, Zhang X, Zhang Y. Serum-volatile organic compounds in the diagnostics of esophageal cancer. Sci Rep 2024; 14:17722. [PMID: 39085271 PMCID: PMC11291479 DOI: 10.1038/s41598-024-67818-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 07/16/2024] [Indexed: 08/02/2024] Open
Abstract
The early diagnosis of esophageal cancer (EC) is extremely challenging due to a lack of effective diagnostic methods. The study presented herein aims to assess whether serum volatile organic compounds (VOCs) could be utilised as emerging diagnostic biomarkers for EC. Gas chromatography-ion mobility spectrometry (GC-IMS) was used to detect VOCs in the serum samples of 55 patients with EC, with samples from 84 healthy controls (HCs) patients analysed as a comparison. All machine learning analyses were based on data from serum VOCs obtained by GC-IMS. A total of 33 substance peak heights were detected in all patient serum samples. The ROC analysis revealed that four machine learning models were effective in facilitating the diagnosis of EC. In addition, the random forests model for 5 VOCs had an AUC of 0.951, with sensitivities and specificities of 94.1 and 96.0%, respectively.
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Affiliation(s)
- Qi Liu
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong, China
- Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, 107 Wenhua Xi Road, Jinan, 250012, Shandong, China
| | - Shuhai Li
- Department of Thoracic Surgery, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong, China
| | - Mai Mao
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong, China
- Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, 107 Wenhua Xi Road, Jinan, 250012, Shandong, China
| | - Xinru Gui
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong, China
- Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, 107 Wenhua Xi Road, Jinan, 250012, Shandong, China
| | - Yanli Zhang
- Department of Clinical Laboratory, Shandong Provincial Third Hospital, Shandong University, Jinan, 250031, Shandong, China.
| | - Yuxiao Zhao
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong, China
- Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, 107 Wenhua Xi Road, Jinan, 250012, Shandong, China
| | - Longchen Yu
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong, China
- Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, 107 Wenhua Xi Road, Jinan, 250012, Shandong, China
| | - Xin Zhang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong, China
- Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, 107 Wenhua Xi Road, Jinan, 250012, Shandong, China
| | - Yi Zhang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong, China.
- Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, 107 Wenhua Xi Road, Jinan, 250012, Shandong, China.
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Liu H, Li K, Xia J, Zhu J, Cheng Y, Zhang X, Ye H, Wang P. Prediction of esophageal cancer risk based on genetic variants and environmental risk factors in Chinese population. BMC Cancer 2024; 24:598. [PMID: 38755535 PMCID: PMC11100074 DOI: 10.1186/s12885-024-12370-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2023] [Accepted: 05/10/2024] [Indexed: 05/18/2024] Open
Abstract
BACKGROUND Results regarding whether it is essential to incorporate genetic variants into risk prediction models for esophageal cancer (EC) are inconsistent due to the different genetic backgrounds of the populations studied. We aimed to identify single-nucleotide polymorphisms (SNPs) associated with EC among the Chinese population and to evaluate the performance of genetic and non-genetic factors in a risk model for developing EC. METHODS A meta-analysis was performed to systematically identify potential SNPs, which were further verified by a case-control study. Three risk models were developed: a genetic model with weighted genetic risk score (wGRS) based on promising SNPs, a non-genetic model with environmental risk factors, and a combined model including both genetic and non-genetic factors. The discrimination ability of the models was compared using the area under the receiver operating characteristic curve (AUC) and the net reclassification index (NRI). The Akaike information criterion (AIC) and Bayesian information criterion (BIC) were used to assess the goodness-of-fit of the models. RESULTS Five promising SNPs were ultimately utilized to calculate the wGRS. Individuals in the highest quartile of the wGRS had a 4.93-fold (95% confidence interval [CI]: 2.59 to 9.38) increased risk of EC compared with those in the lowest quartile. The genetic or non-genetic model identified EC patients with AUCs ranging from 0.618 to 0.650. The combined model had an AUC of 0.707 (95% CI: 0.669 to 0.743) and was the best-fitting model (AIC = 750.55, BIC = 759.34). The NRI improved when the wGRS was added to the risk model with non-genetic factors only (NRI = 0.082, P = 0.037). CONCLUSIONS Among the three risk models for EC, the combined model showed optimal predictive performance and can help to identify individuals at risk of EC for tailored preventive measures.
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Affiliation(s)
- Haiyan Liu
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou City, 450001, Henan Province, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou City, 450052, Henan Province, China
| | - Keming Li
- Zhengzhou Center for Disease Control and Prevention, Zhengzhou City, 450042, Henan Province, China
| | - Junfen Xia
- Office of Health Care, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou City, 450052, Henan Province, China
| | - Jicun Zhu
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou City, 450052, Henan Province, China
| | - Yifan Cheng
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou City, 450001, Henan Province, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou City, 450052, Henan Province, China
| | - Xiaoyue Zhang
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou City, 450001, Henan Province, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou City, 450052, Henan Province, China
| | - Hua Ye
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou City, 450001, Henan Province, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou City, 450052, Henan Province, China
| | - Peng Wang
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou City, 450001, Henan Province, China.
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou City, 450052, Henan Province, China.
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Morales-Berstein F, Biessy C, Viallon V, Goncalves-Soares A, Casagrande C, Hémon B, Kliemann N, Cairat M, Blanco Lopez J, Al Nahas A, Chang K, Vamos E, Rauber F, Bertazzi Levy R, Barbosa Cunha D, Jakszyn P, Ferrari P, Vineis P, Masala G, Catalano A, Sonestedt E, Borné Y, Katzke V, Bajracharya R, Agnoli C, Guevara M, Heath A, Radoï L, Mancini F, Weiderpass E, Huerta JM, Sánchez MJ, Tjønneland A, Kyrø C, Schulze MB, Skeie G, Lukic M, Braaten T, Gunter M, Millett C, Agudo A, Brennan P, Borges MC, Richmond RC, Richardson TG, Davey Smith G, Relton CL, Huybrechts I. Ultra-processed foods, adiposity and risk of head and neck cancer and oesophageal adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition study: a mediation analysis. Eur J Nutr 2024; 63:377-396. [PMID: 37989797 PMCID: PMC10899298 DOI: 10.1007/s00394-023-03270-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Accepted: 10/10/2023] [Indexed: 11/23/2023]
Abstract
PURPOSE To investigate the role of adiposity in the associations between ultra-processed food (UPF) consumption and head and neck cancer (HNC) and oesophageal adenocarcinoma (OAC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS Our study included 450,111 EPIC participants. We used Cox regressions to investigate the associations between the consumption of UPFs and HNC and OAC risk. A mediation analysis was performed to assess the role of body mass index (BMI) and waist-to-hip ratio (WHR) in these associations. In sensitivity analyses, we investigated accidental death as a negative control outcome. RESULTS During a mean follow-up of 14.13 ± 3.98 years, 910 and 215 participants developed HNC and OAC, respectively. A 10% g/d higher consumption of UPFs was associated with an increased risk of HNC (hazard ratio [HR] = 1.23, 95% confidence interval [CI] 1.14-1.34) and OAC (HR = 1.24, 95% CI 1.05-1.47). WHR mediated 5% (95% CI 3-10%) of the association between the consumption of UPFs and HNC risk, while BMI and WHR, respectively, mediated 13% (95% CI 6-53%) and 15% (95% CI 8-72%) of the association between the consumption of UPFs and OAC risk. UPF consumption was positively associated with accidental death in the negative control analysis. CONCLUSIONS We reaffirmed that higher UPF consumption is associated with greater risk of HNC and OAC in EPIC. The proportion mediated via adiposity was small. Further research is required to investigate other mechanisms that may be at play (if there is indeed any causal effect of UPF consumption on these cancers).
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Affiliation(s)
- Fernanda Morales-Berstein
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
| | - Carine Biessy
- Nutrition and Metabolism Branch, International Agency for Research on Cancer/World Health Organization, Lyon, France
| | - Vivian Viallon
- Nutrition and Metabolism Branch, International Agency for Research on Cancer/World Health Organization, Lyon, France
| | - Ana Goncalves-Soares
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Corinne Casagrande
- Nutrition and Metabolism Branch, International Agency for Research on Cancer/World Health Organization, Lyon, France
| | - Bertrand Hémon
- Nutrition and Metabolism Branch, International Agency for Research on Cancer/World Health Organization, Lyon, France
| | - Nathalie Kliemann
- Nutrition and Metabolism Branch, International Agency for Research on Cancer/World Health Organization, Lyon, France
- Cancer Research Center of Santa Catarina, CEPON, Florianópolis, Brazil
| | - Manon Cairat
- Nutrition and Metabolism Branch, International Agency for Research on Cancer/World Health Organization, Lyon, France
- Paris-Saclay University, UVSQ, Inserm "Exposome, Heredity, Cancer and Health" Team, CESP U1018, Gustave Roussy, Villejuif, France
| | - Jessica Blanco Lopez
- Nutrition and Metabolism Branch, International Agency for Research on Cancer/World Health Organization, Lyon, France
| | - Aline Al Nahas
- Nutrition and Metabolism Branch, International Agency for Research on Cancer/World Health Organization, Lyon, France
| | - Kiara Chang
- Public Health Policy Evaluation Unit, School of Public Health, Imperial College London, London, UK
| | - Eszter Vamos
- Public Health Policy Evaluation Unit, School of Public Health, Imperial College London, London, UK
| | - Fernanda Rauber
- Preventive Medicine Department of the Medical School, University of São Paulo, São Paulo, Brazil
- Center for Epidemiological Research in Nutrition and Health, University of São Paulo, São Paulo, Brazil
| | - Renata Bertazzi Levy
- Preventive Medicine Department of the Medical School, University of São Paulo, São Paulo, Brazil
- Center for Epidemiological Research in Nutrition and Health, University of São Paulo, São Paulo, Brazil
| | - Diana Barbosa Cunha
- Hésio Cordeiro Institute of Social Medicine, Department of Epidemiology, Rio de Janeiro State University, Rio de Janeiro, RJ, Brazil
| | - Paula Jakszyn
- 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
- Blanquerna Faculty of Health Sciences, Ramon Llull University, Barcelona, Spain
| | - Pietro Ferrari
- Nutrition and Metabolism Branch, International Agency for Research on Cancer/World Health Organization, Lyon, France
| | - Paolo Vineis
- MRC Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, UK
- Italian Institute of Technology, Genoa, Italy
| | - Giovanna Masala
- Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy
| | - Alberto Catalano
- Centre for Biostatistics, Epidemiology, and Public Health, Department of Clinical and Biological Sciences, University of Turin, 10043, Orbassano, TO, Italy
| | - Emily Sonestedt
- Nutrition Epidemiology, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden
| | - Yan Borné
- Nutrition Epidemiology, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden
| | - Verena Katzke
- Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Rashmita Bajracharya
- Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Claudia Agnoli
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - 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
| | - Alicia Heath
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Loredana Radoï
- Paris-Saclay University, UVSQ, Inserm "Exposome, Heredity, Cancer and Health" Team, CESP U1018, Gustave Roussy, Villejuif, France
| | - Francesca Mancini
- Paris-Saclay University, UVSQ, Inserm "Exposome, Heredity, Cancer and Health" Team, CESP U1018, Gustave Roussy, Villejuif, France
| | - Elisabete Weiderpass
- International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - José María Huerta
- 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
| | - María-José Sánchez
- 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
- Department of Preventive Medicine and Public Health, University of Granada, 18071, Granada, Spain
| | - Anne Tjønneland
- Danish Cancer Society Research Center, Diet, Cancer and Health, Strandboulevarden 49, DK-2100, Copenhagen, Denmark
- Department of Public Health, University of Copenhagen, DK-2200, Copenhagen, Denmark
| | - Cecilie Kyrø
- Danish Cancer Society Research Center, Diet, Cancer and Health, Strandboulevarden 49, DK-2100, Copenhagen, Denmark
| | - 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
| | - Guri Skeie
- Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway
| | - Marko Lukic
- Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway
| | - Tonje Braaten
- Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway
| | - Marc Gunter
- Nutrition and Metabolism Branch, 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
| | - Christopher Millett
- Public Health Policy Evaluation Unit, School of Public Health, Imperial College London, London, UK
- NOVA National School of Public Health, Public Health Research Centre, Comprehensive Health Research Center, CHRC, NOVA University Lisbon, Lisbon, Portugal
| | - 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
| | - Paul Brennan
- Genetic Epidemiology Group, International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - M Carolina Borges
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Rebecca C Richmond
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Tom G Richardson
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - George Davey Smith
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Caroline L Relton
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Inge Huybrechts
- Nutrition and Metabolism Branch, International Agency for Research on Cancer/World Health Organization, Lyon, France
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Ndebia EJ, Kamsu GT. Drinking patterns, alcoholic beverage types, and esophageal cancer risk in Africa: a comprehensive systematic review and meta-analysis. Front Oncol 2023; 13:1310253. [PMID: 38188303 PMCID: PMC10768047 DOI: 10.3389/fonc.2023.1310253] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Accepted: 12/04/2023] [Indexed: 01/09/2024] Open
Abstract
Africa is the continent most affected by esophageal cancer in the world. Alcoholic beverages are controversially blamed, as esophageal cancer is a rare disease in several other countries ranked in the top 10 for consumption of alcoholic beverages. This study aims to conduct a comprehensive systematic review of published literature, statistically summarizing the strength of the association between drinking patterns and types, and the risk of esophageal cancer in Africa. A computerized search of reputable databases such as Medline/PubMed, EMBASE, Web of Science, and African Journals Online was performed to identify relevant studies published up to September 2023. The quality of the studies was evaluated using the Newcastle-Ottawa scale for case-control studies and the Agency for Healthcare Research and Quality tool for cross-sectional studies. A funnel plot and Egger test were utilized to assess potential publication bias. Meta-analyses were conducted using random-effects models with RevMan 5.3 and Stata software to estimate summary effects. The systematic review identified a total of 758,203 studies, primarily from Eastern and Southern Africa. The pooled samples across all studies comprised 29,026 individuals, including 11,237 individuals with cancer and 17,789 individuals without cancer. Meta-analysis revealed a significant association between alcohol consumption and the risk of esophageal cancer (odds ratio [OR] = 1.81; 95% confidence interval [CI], 1.50-2.19). Further analysis based on the frequency of alcoholic beverage consumption indicated a stronger association with daily (OR = 2.38; 95% CI, 1.81-3.13) and weekly (OR = 1.94; 95% CI, 1.32-2.84) drinkers in contrast to occasional drinkers (OR = 1.02; 95% CI, 0.81-1.29). Additionally, consumption of traditional alcoholic beverages was significantly associated with the risk of esophageal cancer in African populations (OR = 2.00; 95% CI, 1.42-2.82). However, no relationship has been established between the exclusive consumption of non-traditional drinks and the risk of esophageal cancer. In conclusion, the results of this study confirm the hypothesis that daily and weekly drinking patterns, significantly increase the risk of esophageal cancer in Africa, while occasional consumption does not show a significant association. Additionally, the consumption of traditional alcoholic beverages is notably linked to the risk of esophageal cancer in African populations.
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7
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Yin D, Zhang Y, Li H, Cheng L. Association of TOP2A and ADH1B with lipid levels and prognosis in patients with lung adenocarcinoma and squamous cell carcinoma. THE CLINICAL RESPIRATORY JOURNAL 2023; 17:1301-1315. [PMID: 37985446 PMCID: PMC10730466 DOI: 10.1111/crj.13717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 10/09/2023] [Accepted: 10/26/2023] [Indexed: 11/22/2023]
Abstract
BACKGROUND Although lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) have different pathological and clinical features, they may share common driver genes. It was found that lipid levels can be used for early diagnosis of NSCLC; however, the relationship between driver genes and genes regulating lipid metabolism and their relationship with patient prognosis needs further investigation. METHODS Genes whose expression was up- or down-regulated in both LUAD and LUSC were identified using the GEO database. Online tools like GEPIA 2, PrognoScan, UALCAN, and TIMER2.0 were used to investigate the association of these gene expressions with the patient's prognosis and lipid regulatory genes. The association between clinical lipid levels and the risk of LUAD and LUSC was analyzed by using a multiple logistic regression model. RESULTS Topoisomerase II alpha (TOP2A) and alcohol dehydrogenase 1B (ADH1B) were identified as the only genes up- and down-regulated in both LUAD and LUSC. TOP2A and ADH1B expression levels significantly correlated with the patient's gender, age, individual cancer stage, histological subtype, nodal metastasis status, and TP53 mutation status. Additionally, only LUAD patients with higher TOP2A or lower ADH1B expressions displayed poor overall and relapse-free survival rates. Moreover, TOP2A levels exhibited a negative correlation with adipose triglyceride lipase (ATGL) and ATP-binding cassette transporter A1 (ABCA1) in both LUAD and LUSC. However, ADH1B showed inverse associations with the above-mentioned genes when compared to TOP2A expressions in both LUAD and LUSC. Furthermore, elevated triglyceride (OR = 1.59; 95% CI = 1.01 to 2.49; P < 0.05) and total cholesterol (OR = 2.45; 95% CI = 1.08 to 5.57; P < 0.05) levels might increase the risk of LUAD. CONCLUSIONS TOP2A and ADH1B can be used as diagnostic markers for LUAD and LUSC, but only as independent prognostic factors for LUAD, and may be involved in lipid metabolism in LUAD patients but not in LUSC. Thus, combining genetic diagnostics with lipid panel tests might be an effective method for an early diagnosis and improved prognosis of LUAD.
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Affiliation(s)
- Dongdong Yin
- First Affiliated Hospital (Huainan First People's Hospital)Anhui University of Science and TechnologyHuainanChina
| | - Yinci Zhang
- First Affiliated Hospital (Huainan First People's Hospital)Anhui University of Science and TechnologyHuainanChina
| | - Hui Li
- First Affiliated Hospital (Huainan First People's Hospital)Anhui University of Science and TechnologyHuainanChina
| | - Longqiang Cheng
- First Affiliated Hospital (Huainan First People's Hospital)Anhui University of Science and TechnologyHuainanChina
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8
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Chen WC, Brandenburg JT, Choudhury A, Hayat M, Sengupta D, Swiel Y, Babb de Villiers C, Ferndale L, Aldous C, Soo CC, Lee S, Curtis C, Newton R, Waterboer T, Sitas F, Bradshaw D, Abnet CC, Ramsay M, Parker MI, Singh E, Lewis CM, Mathew CG. Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations. Am J Hum Genet 2023; 110:1690-1703. [PMID: 37673066 PMCID: PMC10577073 DOI: 10.1016/j.ajhg.2023.08.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 08/11/2023] [Accepted: 08/11/2023] [Indexed: 09/08/2023] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) has a high disease burden in sub-Saharan Africa and has a very poor prognosis. Genome-wide association studies (GWASs) of ESCC in predominantly East Asian populations indicate a substantial genetic contribution to its etiology, but no genome-wide studies have been done in populations of African ancestry. Here, we report a GWAS in 1,686 African individuals with ESCC and 3,217 population-matched control individuals to investigate its genetic etiology. We identified a genome-wide-significant risk locus on chromosome 9 upstream of FAM120A (rs12379660, p = 4.58 × 10-8, odds ratio = 1.28, 95% confidence interval = 1.22-1.34), as well as a potential African-specific risk locus on chromosome 2 (rs142741123, p = 5.49 × 10-8) within MYO1B. FAM120A is a component of oxidative stress-induced survival signals, and the associated variants at the FAM120A locus co-localized with highly significant cis-eQTLs in FAM120AOS in both esophageal mucosa and esophageal muscularis tissue. A trans-ethnic meta-analysis was then performed with the African ESCC study and a Chinese ESCC study in a combined total of 3,699 ESCC-affected individuals and 5,918 control individuals, which identified three genome-wide-significant loci on chromosome 9 at FAM120A (rs12379660, pmeta = 9.36 × 10-10), chromosome 10 at PLCE1 (rs7099485, pmeta = 1.48 × 10-8), and chromosome 22 at CHEK2 (rs1033667, pmeta = 1.47 × 10-9). This indicates the existence of both shared and distinct genetic risk loci for ESCC in African and Asian populations. Our GWAS of ESCC conducted in a population of African ancestry indicates a substantial genetic contribution to ESCC risk in Africa.
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Affiliation(s)
- Wenlong Carl Chen
- National Cancer Registry, National Health Laboratory Service, Johannesburg 2131, South Africa; Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa; Strengthening Oncology Services Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa; Division of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa
| | - Jean-Tristan Brandenburg
- Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa
| | - Ananyo Choudhury
- Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa
| | - Mahtaab Hayat
- Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa; Division of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa
| | - Dhriti Sengupta
- Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa
| | - Yaniv Swiel
- Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa; School of Electrical & Information Engineering, University of the Witwatersrand, Johannesburg 2000, South Africa
| | - Chantal Babb de Villiers
- Division of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa
| | - Lucien Ferndale
- Department of Surgery, Grey's Hospital, Pietermaritzburg 3200, South Africa; College of Health Sciences, School of Clinical Medicine, University of KwaZulu-Natal, Durban 4013, South Africa
| | - Colleen Aldous
- College of Health Sciences, School of Clinical Medicine, University of KwaZulu-Natal, Durban 4013, South Africa
| | - Cassandra C Soo
- Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa
| | - Sang Lee
- Social, Genetic and Development Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, SE5 8AF London, UK; NIHR BioResource Centre Maudsley, South London and Maudsley NHS Foundation Trust, King's College London, SE5 8AF London, UK
| | - Charles Curtis
- Social, Genetic and Development Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, SE5 8AF London, UK; NIHR BioResource Centre Maudsley, South London and Maudsley NHS Foundation Trust, King's College London, SE5 8AF London, UK
| | - Rob Newton
- MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda; University of York, YO10 5DD York, UK
| | - Tim Waterboer
- Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Freddy Sitas
- Burden of Disease Research Unit, South African Medical Research Council, Cape Town 7505, South Africa; Centre for Primary Health Care and Equity, School of Population, University of New South Wales, Sydney, NSW 2052, Australia; Menzies Centre of Health Policy, School of Public Health, University of Sydney, Sydney, NSW 2006, Australia
| | - Debbie Bradshaw
- Burden of Disease Research Unit, South African Medical Research Council, Cape Town 7505, South Africa
| | - Christian C Abnet
- Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20892, USA
| | - Michele Ramsay
- Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa
| | - M Iqbal Parker
- Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7700, South Africa
| | - Elvira Singh
- National Cancer Registry, National Health Laboratory Service, Johannesburg 2131, South Africa; School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa
| | - Cathryn M Lewis
- Social, Genetic and Development Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, SE5 8AF London, UK; Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, King's College London, SE1 9RT London, UK
| | - Christopher G Mathew
- Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa; Division of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa; Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, King's College London, SE1 9RT London, UK.
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Tan Y, Wang Z, Xu M, Li B, Huang Z, Qin S, Nice EC, Tang J, Huang C. Oral squamous cell carcinomas: state of the field and emerging directions. Int J Oral Sci 2023; 15:44. [PMID: 37736748 PMCID: PMC10517027 DOI: 10.1038/s41368-023-00249-w] [Citation(s) in RCA: 149] [Impact Index Per Article: 74.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 08/25/2023] [Accepted: 09/04/2023] [Indexed: 09/23/2023] Open
Abstract
Oral squamous cell carcinoma (OSCC) develops on the mucosal epithelium of the oral cavity. It accounts for approximately 90% of oral malignancies and impairs appearance, pronunciation, swallowing, and flavor perception. In 2020, 377,713 OSCC cases were reported globally. According to the Global Cancer Observatory (GCO), the incidence of OSCC will rise by approximately 40% by 2040, accompanied by a growth in mortality. Persistent exposure to various risk factors, including tobacco, alcohol, betel quid (BQ), and human papillomavirus (HPV), will lead to the development of oral potentially malignant disorders (OPMDs), which are oral mucosal lesions with an increased risk of developing into OSCC. Complex and multifactorial, the oncogenesis process involves genetic alteration, epigenetic modification, and a dysregulated tumor microenvironment. Although various therapeutic interventions, such as chemotherapy, radiation, immunotherapy, and nanomedicine, have been proposed to prevent or treat OSCC and OPMDs, understanding the mechanism of malignancies will facilitate the identification of therapeutic and prognostic factors, thereby improving the efficacy of treatment for OSCC patients. This review summarizes the mechanisms involved in OSCC. Moreover, the current therapeutic interventions and prognostic methods for OSCC and OPMDs are discussed to facilitate comprehension and provide several prospective outlooks for the fields.
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Affiliation(s)
- Yunhan Tan
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
- West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Zhihan Wang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Mengtong Xu
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Bowen Li
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Zhao Huang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Siyuan Qin
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Edouard C Nice
- Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia
| | - Jing Tang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China.
| | - Canhua Huang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.
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10
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Khalatbari A, Castle JD, Li T, Shaker A. Direct and indirect effects of alcohol and its toxic metabolite acetaldehyde on human esophageal myofibroblasts and epithelial cells. ALCOHOL, CLINICAL & EXPERIMENTAL RESEARCH 2023; 47:1297-1311. [PMID: 37128647 PMCID: PMC10524176 DOI: 10.1111/acer.15093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 04/17/2023] [Accepted: 04/24/2023] [Indexed: 05/03/2023]
Abstract
BACKGROUND Mechanisms by which alcohol increases the risk of esophageal squamous cell carcinoma remain undefined. Human esophageal myofibroblasts (HEMFs) subjacent to the squamous epithelium are exposed directly to these agents via epithelial barrier defects and indirectly via factors derived from the exposed epithelium. Our aim was to investigate the cellular biology of HEMFs and HEMF-esophageal epithelial cell interactions in response to alcohol and its toxic metabolite acetaldehyde. METHODS An immortalized HEMF and a human esophageal epithelial cell line (Epi) were treated with alcohol (0 to 200 mM) or acetaldehyde (0 to 100 μM) in a cyclic fashion or incubated with supernatants collected from treated cells. Healthy cell %, reactive oxygen species (ROS), and proliferation were assessed via flow cytometry, luminescence, scratch wound, and colorimetric assays, respectively. A 15-plex multiplex assay was performed on cell supernatants, followed by IL-6 and IL-8 qRT-PCR and ELISA. RESULTS Healthy HEMF decreased to less than 80% at 30 mM alcohol and 70 μM acetaldehyde, with microscopic changes at 40 μM acetaldehyde. HEMF ROS was detected at 100 mM alcohol and 80 μM acetaldehyde. Supernatants from 30 mM alcohol- or 40 μM acetaldehyde-treated HEMFs increased Epi proliferation more than two-fold that of lower doses. In the complementary studies, healthy Epi cells decreased to less than 80% at 50 mM and 70 μM acetaldehyde, with microscopic changes at 40 μM. Supernatants from Epi treated with 50 mM alcohol or 40 μM acetaldehyde increased HEMF proliferation more than two-fold that of lower doses. A multiplex assay of supernatants showed the greatest increase in concentrations of IL-6 and IL-8 in HEMFs and in Epi treated with higher doses of alcohol or acetaldehyde. Neutralization of IL-6 and IL-8 in supernatants of HEMFS and esophageal epithelial cells inhibited the proliferation of Epi and HEMFs, respectively. CONCLUSIONS Alcohol and acetaldehyde doses in which the majority of HEMFs and epithelial cells are healthy, elicit the production of paracrine mediators with pro-proliferative effects on neighboring cells. Understanding the effect of alcohol and acetaldehyde on HEMFs and HEMF-epithelial interactions could help to identify the molecular basis by which alcohol increases the risk for esophageal cancer.
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Affiliation(s)
- Atousa Khalatbari
- University of Southern California, Keck School of Medicine of USC, Department of Medicine, Division of Gastrointestinal and Liver Diseases, Swallowing and Esophageal Disorders Center, 2011 Zonal Avenue, HMR 810, Los Angeles, CA 90089
| | - Joshua D. Castle
- University of Southern California, Keck School of Medicine of USC, Department of Medicine, Division of Gastrointestinal and Liver Diseases, Swallowing and Esophageal Disorders Center, 2011 Zonal Avenue, HMR 810, Los Angeles, CA 90089
| | - Tao Li
- University of Southern California, Keck School of Medicine of USC, Department of Medicine, Division of Gastrointestinal and Liver Diseases, Swallowing and Esophageal Disorders Center, 2011 Zonal Avenue, HMR 810, Los Angeles, CA 90089
| | - Anisa Shaker
- University of Southern California, Keck School of Medicine of USC, Department of Medicine, Division of Gastrointestinal and Liver Diseases, Swallowing and Esophageal Disorders Center, 2011 Zonal Avenue, HMR 810, Los Angeles, CA 90089
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11
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Moreira C, Figueiredo C, Ferreira RM. The Role of the Microbiota in Esophageal Cancer. Cancers (Basel) 2023; 15:cancers15092576. [PMID: 37174041 PMCID: PMC10177416 DOI: 10.3390/cancers15092576] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 04/28/2023] [Accepted: 04/29/2023] [Indexed: 05/15/2023] Open
Abstract
Esophageal cancer is a major health problem, being the seventh most incidence cancer worldwide. Due to the often-late diagnosis and lack of efficient treatments, the overall 5-year survival is as low as 10%. Therefore, understanding the etiology and the mechanisms that drive the development of this type of cancer could improve the management of patients, increasing the chance of achieving a better clinical outcome. Recently, the microbiome has been studied as a putative etiological factor for esophageal cancer. Nevertheless, the number of studies tackling this issue is low, and the heterogeneity in the study design and data analysis has hindered consistent findings. In this work, we reviewed the current literature on the evaluation of the role of microbiota in the development of esophageal cancer. We analyzed the composition of the normal microbiota and the alterations found in precursor lesions, namely Barrett's esophagus and dysplasia, as well as in esophageal cancer. Additionally, we explored how other environmental factors can modify microbiota and contribute to the development of this neoplasia. Finally, we identify critical aspects to be improved in future studies, with the aim of refining the interpretation of the relationship between the microbiome and esophageal cancer.
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Affiliation(s)
- Clara Moreira
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), 4200-135 Porto, Portugal
- Department of Pathology, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal
| | - Ceu Figueiredo
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), 4200-135 Porto, Portugal
- Department of Pathology, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal
- Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal
| | - Rui Manuel Ferreira
- Instituto de Investigação e Inovação em Saúde, Universidade do Porto (i3S), 4200-135 Porto, Portugal
- Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal
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12
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Khan H, Shah MR, Barek J, Malik MI. Cancer biomarkers and their biosensors: A comprehensive review. Trends Analyt Chem 2022. [DOI: 10.1016/j.trac.2022.116813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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13
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Jajosky A, Fels Elliott DR. Esophageal Cancer Genetics and Clinical Translation. Thorac Surg Clin 2022; 32:425-435. [DOI: 10.1016/j.thorsurg.2022.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
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Kumari S, Sharma S, Advani D, Khosla A, Kumar P, Ambasta RK. Unboxing the molecular modalities of mutagens in cancer. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:62111-62159. [PMID: 34611806 PMCID: PMC8492102 DOI: 10.1007/s11356-021-16726-w] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 09/22/2021] [Indexed: 04/16/2023]
Abstract
The etiology of the majority of human cancers is associated with a myriad of environmental causes, including physical, chemical, and biological factors. DNA damage induced by such mutagens is the initial step in the process of carcinogenesis resulting in the accumulation of mutations. Mutational events are considered the major triggers for introducing genetic and epigenetic insults such as DNA crosslinks, single- and double-strand DNA breaks, formation of DNA adducts, mismatched bases, modification in histones, DNA methylation, and microRNA alterations. However, DNA repair mechanisms are devoted to protect the DNA to ensure genetic stability, any aberrations in these calibrated mechanisms provoke cancer occurrence. Comprehensive knowledge of the type of mutagens and carcinogens and the influence of these agents in DNA damage and cancer induction is crucial to develop rational anticancer strategies. This review delineated the molecular mechanism of DNA damage and the repair pathways to provide a deep understanding of the molecular basis of mutagenicity and carcinogenicity. A relationship between DNA adduct formation and cancer incidence has also been summarized. The mechanistic basis of inflammatory response and oxidative damage triggered by mutagens in tumorigenesis has also been highlighted. We elucidated the interesting interplay between DNA damage response and immune system mechanisms. We addressed the current understanding of DNA repair targeted therapies and DNA damaging chemotherapeutic agents for cancer treatment and discussed how antiviral agents, anti-inflammatory drugs, and immunotherapeutic agents combined with traditional approaches lay the foundations for future cancer therapies.
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Affiliation(s)
- Smita Kumari
- Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Bawana Road, Delhi, 110042, India
| | - Sudhanshu Sharma
- Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Bawana Road, Delhi, 110042, India
| | - Dia Advani
- Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Bawana Road, Delhi, 110042, India
| | - Akanksha Khosla
- Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Bawana Road, Delhi, 110042, India
| | - Pravir Kumar
- Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Bawana Road, Delhi, 110042, India
| | - Rashmi K Ambasta
- Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Bawana Road, Delhi, 110042, India.
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Yoo JE, Han K, Shin DW, Kim D, Kim BS, Chun S, Jeon KH, Jung W, Park J, Park JH, Choi KS, Kim JS. Association Between Changes in Alcohol Consumption and Cancer Risk. JAMA Netw Open 2022; 5:e2228544. [PMID: 36001313 PMCID: PMC9403779 DOI: 10.1001/jamanetworkopen.2022.28544] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
IMPORTANCE Although numerous studies have shown an association between alcohol consumption and cancer, how changes in drinking behavior increase or decrease the incidence of cancer is not well understood. OBJECTIVE To investigate the association between the reduction, cessation, or increase of alcohol consumption and the development of alcohol-related cancers and all cancers. DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study analyzed adult beneficiaries in the Korean National Health Insurance Service. Participants (aged ≥40 years) included those who underwent a national health screening in both 2009 and 2011 and had available data on their drinking status. Data were analyzed from April 16 to July 6, 2020. EXPOSURES Alcohol consumption level, which was self-reported by participants in health screening questionnaires, was categorized into none (0 g/d), mild (<15 g/d), moderate (15-29.9 g/d), and heavy (≥30 g/d) drinking. Based on changes in alcohol consumption level from 2009 to 2011, participants were categorized into the following groups: nondrinker, sustainer, increaser, quitter, and reducer. MAIN OUTCOMES AND MEASURES The primary outcome was newly diagnosed alcohol-related cancers (including cancers of the head and neck, esophagus, colorectum, liver, larynx, and female breast), and the secondary outcome was all newly diagnosed cancers (except for thyroid cancer). RESULTS Among the 4 513 746 participants (mean [SD] age, 53.6 [9.6] years; 2 324 172 [51.5%] men), the incidence rate of cancer was 7.7 per 1000 person-years during a median (IQR) follow-up of 6.4 (6.1-6.6) years. Compared with the sustainer groups at each drinking level, the increaser groups had a higher risk of alcohol-related cancers and all cancers. The increased alcohol-related cancer incidence was associated with dose; those who changed from nondrinking to mild (adjusted hazard ratio [aHR], 1.03; 95% CI, 1.00-1.06), moderate (aHR, 1.10; 95% CI, 1.02-1.18), or heavy (aHR, 1.34; 95% CI, 1.23-1.45) drinking levels had an associated higher risk than those who did not drink. Those with mild drinking levels who quit drinking had a lower risk of alcohol-related cancer (aHR, 0.96; 95% CI, 0.92-0.99) than those who sustained their drinking levels. Those with moderate (aHR, 1.07; 95% CI, 1.03-1.12) or heavy (aHR, 1.07; 95% CI, 1.02-1.12) drinking levels who quit drinking had a higher all cancer incidence than those who sustained their levels, but when quitting was sustained, this increase in risk disappeared. Compared with sustained heavy drinking, reduced heavy drinking levels to moderate levels (alcohol-related cancer: aHR, 0.91 [95% CI, 0.86-0.97]; all cancers: aHR, 0.96 [95% CI, 0.92-0.99]) or mild levels (alcohol-related cancer: aHR, 0.92 [95% CI, 0.86-0.98]; all cancers: aHR, 0.92 [95% CI, 0.89-0.96]) were associated with decreased cancer risk. CONCLUSIONS AND RELEVANCE Results of this study showed that increased alcohol consumption was associated with higher risks for alcohol-related and all cancers, whereas sustained quitting and reduced drinking were associated with lower risks of alcohol-related and all cancers. Alcohol cessation and reduction should be reinforced for the prevention of cancer.
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Affiliation(s)
- Jung Eun Yoo
- Department of Family Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
| | - Dong Wook Shin
- Department of Supportive Care Center/Department of Family Medicine, Samsung Medical Center, Seoul, Republic of Korea
- Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Science & Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea
- Department of Digital Health, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea
| | - Dahye Kim
- Department of Medical Statistics, The Catholic University of Korea, Seoul, Republic of Korea
| | - Bong-seong Kim
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
- Department of Medical Statistics, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sohyun Chun
- International Healthcare Center, Samsung Medical Center, Seoul, Republic of Korea
| | - Keun Hye Jeon
- Department of Family Medicine, Cha Gumi Medical Center, Cha University, Gumi-si, Gyeongsangbuk-do, Republic of Korea
| | - Wonyoung Jung
- Department of Supportive Care Center/Department of Family Medicine, Samsung Medical Center, Seoul, Republic of Korea
| | - Jinsung Park
- Department of Urology, Uijeongbu Eulji Medical Center, Eulji University, Uijeongbu-si, Gyeonggi-do, Republic of Korea
| | - Jin Ho Park
- Department of Family Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Kui Son Choi
- Department of Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea
| | - Joo Sung Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
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Choueiry F, Barham A, Zhu J. Analyses of lung cancer-derived volatiles in exhaled breath and in vitro models. Exp Biol Med (Maywood) 2022; 247:1179-1190. [PMID: 35410512 PMCID: PMC9335511 DOI: 10.1177/15353702221082634] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
Lung cancer is one of the leading causes of cancer incidence and cancer-related deaths in the world. Early diagnosis of pulmonary tumors results in improved survival compared to diagnosis with more advanced disease, yet early disease is not reliably indicated by symptoms. Despite of the improved testing and monitoring techniques for lung cancer in the past decades, most diagnostic tests, such as sputum cytology or tissue biopsies, are invasive and risky, rendering them unfeasible for large population screening. The non-invasive analysis of exhaled breath has gained attentions as an innovative screening method to measure chemical alterations within the human volatilome profile as a result of oncogenesis. More importantly, volatile organic compounds (VOCs) have been correlated to the pathophysiology of disease since the source of volatile compounds relies mostly on endogenous metabolic processes that are altered as a result of disease onset. Therefore, studying VOCs emitted from human breath may assist lung cancer diagnosis, treatment monitoring, and other surveillance of this devastating disease. In this mini review, we evaluated recent human studies that have attempted to identify lung cancer-derived volatiles in exhaled breath of patients. We also examined reported volatiles in cell cultures of lung cancer to better understand the origins of cancer-associated VOCs. We highlight the metabolic processes of lung cancer that could be responsible for the endogenous synthesis of these VOCs and pinpoint the protein-encoding genes involved in these pathways. Finally, we highlight the potential value of a breath test in lung cancer and propose prominent areas for future research required for the incorporation of VOCs-based testing into clinical settings.
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Affiliation(s)
- Fouad Choueiry
- Department of Human Sciences, The Ohio State University, Columbus, OH 43210-1132, USA
| | - Addison Barham
- Department of Human Sciences, The Ohio State University, Columbus, OH 43210-1132, USA
| | - Jiangjiang Zhu
- Department of Human Sciences, The Ohio State University, Columbus, OH 43210-1132, USA,James Comprehensive Cancer Center, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA,Jiangjiang Zhu.
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17
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Can gene therapy be used to prevent cancer? Gene therapy for aldehyde dehydrogenase 2 deficiency. Cancer Gene Ther 2022; 29:889-896. [PMID: 34799722 PMCID: PMC9117562 DOI: 10.1038/s41417-021-00399-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 09/24/2021] [Accepted: 10/08/2021] [Indexed: 11/08/2022]
Abstract
Approximately 8% of the world population and 35-45% of East Asians are carriers of the hereditary disorder aldehyde dehydrogenase 2 (ALDH2) deficiency. ALDH2 plays a central role in the liver to metabolize ethanol. With the common E487K variant, there is a deficiency of ALDH2 function; when ethanol is consumed, there is a systemic accumulation of acetaldehyde, an intermediate product in ethanol metabolism. In ALDH2-deficient individuals, ethanol consumption acutely causes the "Alcohol Flushing Syndrome" with facial flushing, tachycardia, nausea, and headaches. With chronic alcohol consumption, ALDH2 deficiency is associated with a variety of disorders, including a remarkably high risk for aerodigestive tract cancers. Acetaldehyde is a known carcinogen. The epidemiologic data relating to the association of ALDH2 deficiency and cancer risk are striking: ALDH2 homozygotes who are moderate-to-heavy consumers of ethanol have a 7-12-fold increased risk for esophageal cancer, making ALDH2 deficiency the most common hereditary disorder associated with an increased cancer risk. In this review, we summarize the genetics and biochemistry of ALDH2, the epidemiology of cancer risk associated with ALDH2 deficiency, the metabolic consequences of ethanol consumption associated with ALDH2 deficiency, and gene therapy strategies to correct ALDH2 deficiency and its associated cancer risk. With the goal of reducing the risk of aerodigestive tract cancers, in the context that ALDH2 is a hereditary disorder and ALDH2 functions primarily in the liver, ALDH2 deficiency is an ideal target for the application of adeno-associated virus-mediated liver-directed gene therapy to prevent cancer.
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18
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Soroush A, Etemadi A, Abrams JA. Non-Acid Fluid Exposure and Esophageal Squamous Cell Carcinoma. Dig Dis Sci 2022; 67:2754-2762. [PMID: 34236559 DOI: 10.1007/s10620-021-07127-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 06/22/2021] [Indexed: 12/11/2022]
Abstract
Esophageal squamous cell carcinoma (ESCC) accounts for the large majority of esophageal cancer cases worldwide. In this review, we examine the potential role of non-acidic fluid (NAF) exposure in ESCC carcinogenesis. Esophageal NAF consists of a mixture of salivary, esophageal, gastric, and duodenal fluids, containing inflammatory constituents such as digestive enzymes and bile acids that induce DNA damage, as well as known carcinogens such as acetaldehyde and N-nitrosamines. Exposure to NAF can occur in the setting of increased non-acid reflux, decreased gastric acidity, and decreased esophageal fluid clearance. Non-acid reflux has been associated with ESCC in small observational studies, and in animal models bile reflux can promote the development of ESCC. Associations have been found between increased ESCC risk and atrophic gastritis, a history of partial gastrectomy, and proton pump inhibitor use, all of which raise the pH of refluxate. Additionally, a minimally or non-acidic gastric environment contains an altered microbiome that can increase the production of acetaldehyde and N-nitrosamines. Esophageal motility disorders such as achalasia and opioid-induced esophageal dysfunction result in increased stasis and exposure to these potentially proinflammatory constituents of NAF. NAF may promote the development of ESCC via multiple mechanisms and is an understudied area of research.
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Affiliation(s)
- Ali Soroush
- Department of Medicine, Columbia University Irving Medical Center, 630 W 168th Street, P&S 3-401, New York, NY, 10032, USA.
| | - Arash Etemadi
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 630 W 168th Street, P&S 3-401, Bethesda, MD, USA
| | - Julian A Abrams
- Department of Medicine, Columbia University Irving Medical Center, 630 W 168th Street, P&S 3-401, New York, NY, 10032, USA
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19
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Alcohol Consumption, ALDH2 Polymorphism as Risk Factors for Upper Aerodigestive Tract Cancer Progression and Prognosis. Life (Basel) 2022; 12:life12030348. [PMID: 35330099 PMCID: PMC8956056 DOI: 10.3390/life12030348] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 02/22/2022] [Accepted: 02/23/2022] [Indexed: 12/17/2022] Open
Abstract
The upper aerodigestive tract (UADT) is highly susceptible to multiple primary cancers originated from squamous epithelia and constitutes a field of cancerization. Patients with head and neck cancer (head and neck squamous cell carcinoma, HNSCC) are at high risk of developing multiple cancers in the esophagus (esophageal squamous cell carcinoma, ESCC). Conversely, esophageal cancer patients are prone to develop multiple primary tumors in the head and neck region. The East Asian-specific dysfunctional ALDH2*2 missense mutation is a genetic risk factor for UADT cancer. It is not only associated with increased incidences of UADT cancer, but is also implicated in faster cancer progression and poorer prognosis. Alcohol use is a major lifestyle risk factor which causes UADT cancer among ALDH2*2 carriers. The accumulation of the immediate metabolite of alcohol, acetaldehyde, is likely the genotoxic agents that is involved in the process of tumorigenesis. This review summarizes recent publications on the risk and association of ALDH2*2 mutation, alcohol consumption in synchronous, metachronous UADT cancer. Possible molecular mechanisms involved in cancer initiation, progress and prognosis are discussed. The review also highlights a need for precision medicine-based preventive and therapeutic strategies by integrating lifestyle and genetic risk factors, such as alcohol consumption, genotypes of the alcohol metabolizing genes, ADH1B and ALDH2, into a risk assessment model for better screening, surveillance and treatment outcome.
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20
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Suzuki T, Eguchi A, Shigefuku R, Nagao S, Morikawa M, Sugimoto K, Iwasa M, Takei Y. Accuracy of carbohydrate-deficient transferrin as a biomarker of chronic alcohol abuse during treatment for alcoholism. Hepatol Res 2022; 52:120-127. [PMID: 33797850 DOI: 10.1111/hepr.13642] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 02/26/2021] [Accepted: 03/21/2021] [Indexed: 12/12/2022]
Abstract
AIM Clinical evaluations are generally used to verify the effectiveness of detoxification treatments for alcohol dependence, but new objective biomarkers are essential for accurate diagnosis. We aim to assess the accuracy of carbohydrate-deficient transferrin (%CDT) in a cohort of Japanese patients admitted to a psychiatric hospital specializing in alcohol dependence. In addition, we investigated the kinetics of %CDT during alcohol moderation or cessation. METHODS The study cohort consisted of 126 alcohol-dependent patients. The levels of serum %CDT were assessed by the N Latex CDT direct immunonephelometric assay. RESULTS Alcohol consumption was significantly correlated with %CDT. The only independent predictive factor of alcohol consumption was %CDT, with glutamyltranspeptidase (GGT) and albumin-bilirubin score proving insufficient. The cut-off value of %CDT was 1.9% with high sensitivity and specificity in detecting alcohol abstinence beyond 30 days (68.6% sensitivity, 91.8% specificity) and excessive alcohol drinking (77.9% sensitivity, 77.1% specificity). The %CDT levels were significantly decreased at 30 days of abstinence when compared with baseline. Notably, %CDT values were significantly changed even in the light alcohol drinking cohort (p = 0.0009), whereas GGT levels were not significantly changed. CONCLUSIONS Our results indicate that %CDT is an accurate and specific biomarker of alcohol consumption and is useful in detecting alcohol abstinence even in a low alcohol intake patient cohort. These results suggest that %CDT could be a useful objective biomarker of chronic alcohol abuse during clinical treatment for alcoholism.
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Affiliation(s)
- Tatsuya Suzuki
- Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Japan.,Department of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Akiko Eguchi
- Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Ryuta Shigefuku
- Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Japan
| | | | | | - Kazushi Sugimoto
- Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Motoh Iwasa
- Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Yoshiyuki Takei
- Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Japan
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21
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Duijster JW, Franz E, Neefjes J, Mughini-Gras L. Bacterial and Parasitic Pathogens as Risk Factors for Cancers in the Gastrointestinal Tract: A Review of Current Epidemiological Knowledge. Front Microbiol 2021; 12:790256. [PMID: 34956157 PMCID: PMC8692736 DOI: 10.3389/fmicb.2021.790256] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 11/11/2021] [Indexed: 12/12/2022] Open
Abstract
The oncogenic potential of viral infections is well established and documented for many years already. However, the contribution of (commensal) bacteria and parasites to the development and progression of cancers has only recently gained momentum, resulting in a rapid growth of publications on the topic. Indeed, various bacteria and parasites have been suggested to play a role in the development of gastrointestinal cancer in particular. Therefore, an overview of the current epidemiological knowledge on the association between infections with bacteria and parasites and cancers of the gastrointestinal tract is needed. In this review, we summarized the methodological characteristics and main results of epidemiological studies investigating the association of 10 different bacteria (Bacteroides fragilis, Campylobacter spp., Clostridium spp., Enterococcus faecalis, Escherichia coli, Fusobacterium nucleatum, Porphyromonas gingivalis, non-typhoidal Salmonella, Salmonella Typhi, and Streptococcus spp.) and three parasites (Cryptosporidium spp., Schistosoma spp., and Strongyloides stercoralis) with gastrointestinal cancer. While the large body of studies based on microbiome sequencing provides valuable insights into the relative abundance of different bacterial taxa in cancer patients as compared to individuals with pre-malignant conditions or healthy controls, more research is needed to fulfill Koch's postulates, possibly making use of follow-up data, to assess the complex role of bacterial and parasitic infections in cancer epidemiology. Studies incorporating follow-up time between detection of the bacterium or parasite and cancer diagnosis remain valuable as these allow for estimation of cause-effect relationships.
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Affiliation(s)
- Janneke W. Duijster
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands
- Department of Cell and Chemical Biology, Oncode Institute, Leiden University Medical Center, Leiden, Netherlands
| | - Eelco Franz
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands
| | - Jacques Neefjes
- Department of Cell and Chemical Biology, Oncode Institute, Leiden University Medical Center, Leiden, Netherlands
| | - Lapo Mughini-Gras
- Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands
- Institute for Risk Assessment Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands
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22
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Gelernter J, Polimanti R. Genetics of substance use disorders in the era of big data. Nat Rev Genet 2021; 22:712-729. [PMID: 34211176 PMCID: PMC9210391 DOI: 10.1038/s41576-021-00377-1] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/07/2021] [Indexed: 02/06/2023]
Abstract
Substance use disorders (SUDs) are conditions in which the use of legal or illegal substances, such as nicotine, alcohol or opioids, results in clinical and functional impairment. SUDs and, more generally, substance use are genetically complex traits that are enormously costly on an individual and societal basis. The past few years have seen remarkable progress in our understanding of the genetics, and therefore the biology, of substance use and abuse. Various studies - including of well-defined phenotypes in deeply phenotyped samples, as well as broadly defined phenotypes in meta-analysis and biobank samples - have revealed multiple risk loci for these common traits. A key emerging insight from this work establishes a biological and genetic distinction between quantity and/or frequency measures of substance use (which may involve low levels of use without dependence), versus symptoms related to physical dependence.
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Affiliation(s)
- Joel Gelernter
- Department of Psychiatry, Yale University School of Medicine, West Haven, CT, USA.
- Department of Psychiatry, Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA.
| | - Renato Polimanti
- Department of Psychiatry, Yale University School of Medicine, West Haven, CT, USA
- Department of Psychiatry, Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA
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23
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Shimonosono M, Tanaka K, Flashner S, Takada S, Matsuura N, Tomita Y, Sachdeva UM, Noguchi E, Sangwan V, Ferri L, Momen-Heravi F, Yoon AJ, Klein-Szanto AJ, Diehl JA, Nakagawa H. Alcohol Metabolism Enriches Squamous Cell Carcinoma Cancer Stem Cells That Survive Oxidative Stress via Autophagy. Biomolecules 2021; 11:1479. [PMID: 34680112 PMCID: PMC8533166 DOI: 10.3390/biom11101479] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 09/30/2021] [Accepted: 10/04/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Alcohol (ethanol) consumption is a major risk factor for head and neck and esophageal squamous cell carcinomas (SCCs). However, how ethanol (EtOH) affects SCC homeostasis is incompletely understood. METHODS We utilized three-dimensional (3D) organoids and xenograft tumor transplantation models to investigate how EtOH exposure influences intratumoral SCC cell populations including putative cancer stem cells defined by high CD44 expression (CD44H cells). RESULTS Using 3D organoids generated from SCC cell lines, patient-derived xenograft tumors, and patient biopsies, we found that EtOH is metabolized via alcohol dehydrogenases to induce oxidative stress associated with mitochondrial superoxide generation and mitochondrial depolarization, resulting in apoptosis of the majority of SCC cells within organoids. However, CD44H cells underwent autophagy to negate EtOH-induced mitochondrial dysfunction and apoptosis and were subsequently enriched in organoids and xenograft tumors when exposed to EtOH. Importantly, inhibition of autophagy increased EtOH-mediated apoptosis and reduced CD44H cell enrichment, xenograft tumor growth, and organoid formation rate. CONCLUSIONS This study provides mechanistic insights into how EtOH may influence SCC cells and establishes autophagy as a potential therapeutic target for the treatment of EtOH-associated SCC.
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Affiliation(s)
- Masataka Shimonosono
- Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (S.F.); (S.T.); (N.M.); (Y.T.); (U.M.S.); (F.M.-H.); (A.J.Y.)
| | - Koji Tanaka
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan;
| | - Samuel Flashner
- Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (S.F.); (S.T.); (N.M.); (Y.T.); (U.M.S.); (F.M.-H.); (A.J.Y.)
| | - Satoshi Takada
- Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (S.F.); (S.T.); (N.M.); (Y.T.); (U.M.S.); (F.M.-H.); (A.J.Y.)
| | - Norihiro Matsuura
- Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (S.F.); (S.T.); (N.M.); (Y.T.); (U.M.S.); (F.M.-H.); (A.J.Y.)
| | - Yasuto Tomita
- Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (S.F.); (S.T.); (N.M.); (Y.T.); (U.M.S.); (F.M.-H.); (A.J.Y.)
| | - Uma M. Sachdeva
- Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (S.F.); (S.T.); (N.M.); (Y.T.); (U.M.S.); (F.M.-H.); (A.J.Y.)
- Department of Surgery, Division of Thoracic Surgery, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Eishi Noguchi
- Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USA;
| | - Veena Sangwan
- Department of Surgery, Montreal General Hospital, McGill University, Montreal, QC H3G 1A4, Canada; (V.S.); (L.F.)
| | - Lorenzo Ferri
- Department of Surgery, Montreal General Hospital, McGill University, Montreal, QC H3G 1A4, Canada; (V.S.); (L.F.)
| | - Fatemeh Momen-Heravi
- Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (S.F.); (S.T.); (N.M.); (Y.T.); (U.M.S.); (F.M.-H.); (A.J.Y.)
- Cancer Biology and Immunology Laboratory, College of Dental Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA
| | - Angela J. Yoon
- Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (S.F.); (S.T.); (N.M.); (Y.T.); (U.M.S.); (F.M.-H.); (A.J.Y.)
- Department of Pathology & Cell Biology, Division of Oral & Maxillofacial Pathology, Columbia University Irving Medical Center, New York, NY 10032, USA
| | | | - J. Alan Diehl
- Case Comprehensive Cancer Center, Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA;
| | - Hiroshi Nakagawa
- Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (S.F.); (S.T.); (N.M.); (Y.T.); (U.M.S.); (F.M.-H.); (A.J.Y.)
- Department of Medicine, Division of Digestive and Liver Diseases, Columbia University Irving Medical Center, New York, NY 10032, USA
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Metachronous carcinogenesis of superficial esophagus squamous cell carcinoma after endoscopic submucosal dissection: incidence and risk stratification during long-term observation. Esophagus 2021; 18:806-816. [PMID: 33974189 DOI: 10.1007/s10388-021-00848-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Accepted: 04/21/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND This study aimed to reveal long-term outcomes, such as incidence of metachronous esophageal and head and neck squamous cell carcinomas and overall survival rate, through long-term observation of patients with esophageal carcinoma post-endoscopic submucosal dissection. METHODS Risk of metachronous carcinogenesis was evaluated in 88 patients with intramucosal esophageal carcinoma (without history of metachronous esophageal or head and neck squamous cell carcinomas) who underwent endoscopic submucosal dissection from 2007 to 2008 and were endoscopically observed for > 3 years. Histologically, the papillary vessel is defined as the clock gear-like structure composed of capillaries directly penetrating the epithelium (starting from the lamina propria) and covering at least two-thirds of it, around which the tumor cells are arranged in a spiral pattern. RESULTS Median endoscopic follow-up period was 11.0 years. Cumulative 2-, 5-, and 10-year metachronous esophageal carcinoma rates were 11.4%, 20.6%, and 39.3%, respectively. Stepwise multivariate Cox proportional hazard regression analysis identified multiple Lugol-voiding lesions (LVLs) as the single significant independent predictor. Cumulative 2-, 5-, and 10-year metachronous head and neck squamous cell carcinoma rates were 6.9%, 10.4%, and 19.6%, respectively. Stepwise multivariate Cox proportional hazard regression analysis identified multiple LVLs, Brinkman index, papillary vessel, and younger age as significant predictive factors. Overall post-endoscopic submucosal dissection survival rates were 98.8% and 87.5% at 5 and 10 years, respectively. CONCLUSION Patients with a history of esophageal carcinoma remain at risk for metachronous carcinogenesis even > 5 years after endoscopic submucosal dissection. Thus, long-term follow-up is important.
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25
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Li Z, Liu Y, Dou L, Zhang Y, He S, Zhao D, Zhang W, Wang G. The effects of smoking and drinking on the oral and esophageal microbiota of healthy people. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1244. [PMID: 34532381 PMCID: PMC8421972 DOI: 10.21037/atm-21-3264] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 07/15/2021] [Indexed: 01/04/2023]
Abstract
Background To explore the effects of smoking and drinking on the microbiota in the saliva and three segments of the esophagus (upper, middle, and lower) in healthy individuals. Methods Paired saliva and brush specimens were obtained from 76 participants who underwent upper gastrointestinal (UGI) endoscopic examination for UGI cancer screening. The esophageal microbiota was investigated by 16S rRNA gene profiling via next-generation sequencing. Results The saliva samples from non-smoking and non-drinking participants had a greater abundance of Neisseria, Prevotella, Porphyromonas, and Rothia, and lower levels of Streptococcus, Actinobacillus, and Haemophilus compared to the esophagus. There were no significant differences in the abundance of most bacterial genera in the upper, middle, and lower oesophagus. Similarly, in the saliva of patients who smoke and drink, there was a higher prevalence of Neisseria, Prevotella, Porphyromonas, Fusobacterium, and Rothia, and a lower prevalence of Streptococcus, Actinobacillus, and Haemophilus compared to the esophagus. There were no significant differences in the abundance of most genera in the upper, middle, and lower esophagus of patients with a history of drinking and smoking. There were slight differences in the microbiota between smoking and drinking individuals and non-smoking and non-drinking individuals. Conclusions This pilot study demonstrated microbial diversity at different taxonomic levels in the oral cavity and esophagus of non-drinking and non-smoking individuals, as well as healthy people who drink and smoke . There was a slight difference in the microbiota between non-drinking and non-smoking people and individuals with a history of drinking and smoking. These results suggested that oral or esophageal cancer caused by smoking and drinking may not be mediated by mechanisms that affect surface microorganisms.
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Affiliation(s)
- Zhengqi Li
- Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yong Liu
- Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lizhou Dou
- Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yueming Zhang
- Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shun He
- Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Deli Zhao
- Cancer Center, Feicheng People's Hospital, Feicheng, China
| | - Wei Zhang
- Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Guiqi Wang
- Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Yoo JE, Shin DW, Han K, Kim D, Jeong SM, Koo HY, Yu SJ, Park J, Choi KS. Association of the Frequency and Quantity of Alcohol Consumption With Gastrointestinal Cancer. JAMA Netw Open 2021; 4:e2120382. [PMID: 34406403 PMCID: PMC8374610 DOI: 10.1001/jamanetworkopen.2021.20382] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
IMPORTANCE Although total alcohol consumption is a known risk factor for gastrointestinal (GI) cancers, few studies have attempted to assess the pattern of alcohol drinking in association with GI cancers. OBJECTIVE To evaluate the relative association of the frequency of drinking vs the amount of alcohol consumed per occasion with the development of GI cancers. DESIGN, SETTING, AND PARTICIPANTS A population-based retrospective cohort study used data from the Korean National Health Insurance System database on 11 737 467 participants without cancer who underwent a national health screening program from January 1, 2009, to December 31, 2010. Participants were followed up from the year after their health screening date until they received a diagnosis of GI cancer, death, or December 31, 2017. The median follow-up duration was 6.4 years (interquartile range, 6.4-7.4 years). Statistical analysis was performed from January 1, 2019, to March 31, 2020. EXPOSURES Weekly alcohol consumption (nondrinker [0 g/week], mild drinker [0-104 g/week], moderate drinker [105-209 g/week], and heavy drinker [≥210 g/week]), drinking frequency, and amount per occasion. MAIN OUTCOMES AND MEASURES Incident GI cancers at 6 specific sites (esophagus, stomach, colorectal, liver, biliary, and pancreas). RESULTS Among 11 737 467 participants (6 124 776 women [52.2%]; mean [SD] age, 54.6 [10.4] years), 319 202 (2.7%) developed GI cancer. Compared with nondrinkers, the risk of GI cancer was higher for mild drinkers (adjusted hazard ratio [aHR], 1.04; 95% CI, 1.03-1.05), moderate drinkers (aHR, 1.14; 95% CI, 1.12-1.15), and heavy drinkers (aHR, 1.28; 95% CI, 1.26-1.29). The risk of GI cancer increased linearly with the frequency of drinking in a dose-dependent manner (aHR, 1.39; 95% CI, 1.36-1.41 for individuals who drink every day). In contrast, the risk of GI cancer appeared to increase with consumption up to 5 to 7 units per occasion (aHR, 1.15; 95% CI, 1.14-1.16), and then the HRs were no higher for those with a higher intake per session than 5 to 7 units (8-14 units per occasion: aHR, 1.11; 95% CI, 1.09-1.12; >14 units per occasion: aHR, 1.11; 95% CI, 1.08-1.14). Given similar weekly alcohol consumption levels, the risk of GI cancer increased with a higher frequency of drinking and decreased with a higher amount per occasion. Risk patterns for 6 specific cancers were generally similar to that of all GI cancers. CONCLUSIONS AND RELEVANCE In this cohort study, frequent drinking was a more important risk factor for incident GI cancers than the amount of alcohol consumed per occasion. Individuals should be cautioned about regular consumption of small amounts of alcohol in addition to the total amount of alcohol consumption or amount per occasion.
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Affiliation(s)
- Jung Eun Yoo
- Department of Family Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Dong Wook Shin
- Supportive Care Center, Department of Family Medicine, Samsung Medical Center, Seoul, Republic of Korea
- Department of Clinical Research Design & Evaluation, Samsung Advanced Institute for Health Science & Technology, Sungkyunkwan University, Seoul, Republic of Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
| | - Dahye Kim
- Department of Medical Statistics, The Catholic University of Korea, Seoul, Republic of Korea
| | - Su-Min Jeong
- Supportive Care Center, Department of Family Medicine, Samsung Medical Center, Seoul, Republic of Korea
- Department of Family Medicine, Seoul Metropolitan Government–Seoul National University Boramae Medical Center, Seoul, Republic of Korea
- Department of Family Medicine, Seoul National University Health Service Center, Seoul, Republic of Korea
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Hye Yeon Koo
- Health Promotion Center, Cha Bundang Medical Center, Seongnam, Republic of Korea
| | - Su Jong Yu
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea
- Biomedical Research Institute, Center for Medical Innovation, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jinsung Park
- Department of Urology, Uijeongbu Eulji Medical Center, Eulji University, Uijeongbu-si, Republic of Korea
| | - Kui Son Choi
- Department of Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea
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Rodriguez FD, Coveñas R. Biochemical Mechanisms Associating Alcohol Use Disorders with Cancers. Cancers (Basel) 2021; 13:cancers13143548. [PMID: 34298760 PMCID: PMC8306032 DOI: 10.3390/cancers13143548] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 07/01/2021] [Accepted: 07/14/2021] [Indexed: 02/06/2023] Open
Abstract
Simple Summary Of all yearly deaths attributable to alcohol consumption globally, approximately 12% are due to cancers, representing approximately 0.4 million deceased individuals. Ethanol metabolism disturbs cell biochemistry by targeting the structure and function of essential biomolecules (proteins, nucleic acids, and lipids) and by provoking alterations in cell programming that lead to cancer development and cancer malignancy. A better understanding of the metabolic and cell signaling realm affected by ethanol is paramount to designing effective treatments and preventive actions tailored to specific neoplasias. Abstract The World Health Organization identifies alcohol as a cause of several neoplasias of the oropharynx cavity, esophagus, gastrointestinal tract, larynx, liver, or female breast. We review ethanol’s nonoxidative and oxidative metabolism and one-carbon metabolism that encompasses both redox and transfer reactions that influence crucial cell proliferation machinery. Ethanol favors the uncontrolled production and action of free radicals, which interfere with the maintenance of essential cellular functions. We focus on the generation of protein, DNA, and lipid adducts that interfere with the cellular processes related to growth and differentiation. Ethanol’s effects on stem cells, which are responsible for building and repairing tissues, are reviewed. Cancer stem cells (CSCs) of different origins suffer disturbances related to the expression of cell surface markers, enzymes, and transcription factors after ethanol exposure with the consequent dysregulation of mechanisms related to cancer metastasis or resistance to treatments. Our analysis aims to underline and discuss potential targets that show more sensitivity to ethanol’s action and identify specific metabolic routes and metabolic realms that may be corrected to recover metabolic homeostasis after pharmacological intervention. Specifically, research should pay attention to re-establishing metabolic fluxes by fine-tuning the functioning of specific pathways related to one-carbon metabolism and antioxidant processes.
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Affiliation(s)
- Francisco D. Rodriguez
- Department of Biochemistry and Molecular Biology, Faculty of Chemistry, University of Salamanca, 37007 Salamanca, Spain
- Group GIR USAL: BMD (Bases Moleculares del Desarrollo), 37007 Salamanca, Spain;
- Correspondence: ; Tel.: +34-677-510-030
| | - Rafael Coveñas
- Group GIR USAL: BMD (Bases Moleculares del Desarrollo), 37007 Salamanca, Spain;
- Institute of Neurosciences of Castilla y León (INCYL), Laboratory of Neuroanatomy of the Peptidergic Systems, University of Salamanca, 37007 Salamanca, Spain
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Du XY, Wen L, Hu YY, Deng SQ, Xie LC, Jiang GB, Yang GL, Niu YM. Association Between the Aldehyde Dehydrogenase-2 rs671 G>A Polymorphism and Head and Neck Cancer Susceptibility: A Meta-Analysis in East Asians. Alcohol Clin Exp Res 2021; 45:307-317. [PMID: 33283290 DOI: 10.1111/acer.14527] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 11/23/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Aldehyde dehydrogenase-2 (ALDH2) plays an important role in the alcohol detoxification and acetaldehyde metabolism. Published studies have demonstrated some inconsistent associations between ALDH2 rs671 G>A polymorphism and head and neck cancer (HNC) risk. METHODS A meta-analysis was performed to provide pooled data on the association between the ALDH2 rs671 G>A polymorphism and HNC risk. Electronic databases were searched to identify relevant studies. Odds ratios and 95% confidence intervals (CIs) were used to examine the pooled effect size of each genetic model. In addition, heterogeneity test, accumulative analysis, sensitivity analysis, and publication bias were conducted to test the statistical power. RESULTS Thirteen publications (14 independent case-control studies) involving 10,939 subjects were selected. The stratified analysis indicated that both light/moderated drinking (e.g., GA vs. GG: OR = 1.47, 95% CI = 1.16 to 1.86, p < 0.01, I2 = 81.1%) and heavy drinking would increase HNC risk with rs671 G>A mutation (e.g., GA vs. GG: OR = 2.30, 95% CI = 1.11 to 4.77, p = 0.03, I2 = 81.9%). CONCLUSIONS In summary, this meta-analysis suggested that the ALDH2 rs671 G>A polymorphism may play an important synergistic effect in the pathogenesis of HNC development in East Asians.
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Affiliation(s)
- Xin-Ya Du
- From the, Department of Stomatology, (X-YD, G-LY, Y-MN), The People's Hospital of Longhua Shenzhen, Affiliated Longhua People's Hospital, Southern Medicine University, Shenzhen, China
| | - Li Wen
- Department of Dermatology, (LW), Suizhou Hospital, Hubei University of Medicine, Suizhou, China
| | - Yuan-Yuan Hu
- Department of Stomatology, (Y-YH, L-CX, Y-MN), Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan, China.,Department of Research Affair Management, (Y-YH, S-QD), Gongli Hospital, the Secondary Military Medical University, Shanghai, China.,Department of Radiology and Stomatology, (Y-YH, G-BJ), Suizhou Hospital, Hubei University of Medicine, Suizhou, China
| | - Sheng-Qiong Deng
- Department of Research Affair Management, (Y-YH, S-QD), Gongli Hospital, the Secondary Military Medical University, Shanghai, China
| | - Long-Chuan Xie
- Department of Stomatology, (Y-YH, L-CX, Y-MN), Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan, China
| | - Guang-Bin Jiang
- Department of Radiology and Stomatology, (Y-YH, G-BJ), Suizhou Hospital, Hubei University of Medicine, Suizhou, China
| | - Gong-Li Yang
- From the, Department of Stomatology, (X-YD, G-LY, Y-MN), The People's Hospital of Longhua Shenzhen, Affiliated Longhua People's Hospital, Southern Medicine University, Shenzhen, China.,Department of Gastroenterology, (G-Li Y), Shenzhen University General Hospital, Shenzhen University, Shenzhen, China
| | - Yu-Ming Niu
- From the, Department of Stomatology, (X-YD, G-LY, Y-MN), The People's Hospital of Longhua Shenzhen, Affiliated Longhua People's Hospital, Southern Medicine University, Shenzhen, China.,Department of Stomatology, (Y-YH, L-CX, Y-MN), Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan, China
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Zhang J, Wu H, Wang R. Metabolic syndrome and esophageal cancer risk: a systematic review and meta‑analysis. Diabetol Metab Syndr 2021; 13:8. [PMID: 33468224 PMCID: PMC7816502 DOI: 10.1186/s13098-021-00627-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Accepted: 01/08/2021] [Indexed: 12/30/2022] Open
Abstract
OBJECTIVE Many clinical studies evaluating the relationship between metabolic syndrome and esophageal cancer yielded uncertain results. The purpose of this study is to systematically assess the relationship between metabolic syndrome and esophageal cancer. METHODS We searched clinical studies on metabolic syndrome and esophageal cancer risk in PubMed, Embase, and the Cochrane Library. Meta-analysis was conducted by RevMan 5.3 softwares. RESULTS A total of four cohort studies and two case-control studies met eligibility criteria and were included in the meta-analysis. Meta-analysis using a fixed-effect model indicated that MetS was related with a higher risk of EC (OR: 1.16, 95% CI 1.08-1.25). Subgroup analyses grouped by pathological types showed that MetS was related with a higher risk of EAC (OR: 1.19, 95% CI 1.10-1.28). Subgroup analyses grouped by metabolic conditions showed hyperglycemia (OR: 1.12, 95% CI 1.03-1.21),hypertension (OR: 1.23, 95% CI 1.04-1.46), obesity (OR: 1.40, 95% CI 1.22-1.60, P < 0.05) were related with a higher risk of EAC. CONCLUSIONS Overall, our meta-analysis provides high quality evidence that metabolic syndrome was related with a higher risk of EAC. Among the individual components of the metabolic syndrome, hyperglycemia, hypertension and obesity may be the key factors.
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Affiliation(s)
- Jinjia Zhang
- Department of General Practice, Second Hospital of Hebei Medical University, Heping Western Road No. 215, Shijiazhuang, 050000 Hebei China
| | - Huadong Wu
- Department of Gastrointestinal Surgery, Second Hospital of Hebei Medical University, Shijiazhuang, 050000 Hebei China
| | - Rongying Wang
- Department of General Practice, Second Hospital of Hebei Medical University, Heping Western Road No. 215, Shijiazhuang, 050000 Hebei China
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Tian W, Guo J, Zhang Q, Fang S, Zhou R, Hu J, Wang M, Zhang Y, Guo JM, Chen Z, Zhu J, Zheng C. The discovery of novel small molecule allosteric activators of aldehyde dehydrogenase 2. Eur J Med Chem 2020; 212:113119. [PMID: 33383258 DOI: 10.1016/j.ejmech.2020.113119] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 12/01/2020] [Accepted: 12/17/2020] [Indexed: 11/17/2022]
Abstract
Aldehyde dehydrogenase 2 (ALDH2) plays important role in ethanol metabolism, and also serves as an important shield from the damage occurring under oxidative stress. A special inactive variant was found carried by 35-45% of East Asians. The variant carriers have recently been found at the higher risk for the diseases related to the damage occurring under oxidative stress, such as cardiovascular and cerebrovascular diseases. As a result, ALDH2 activators may potentially serve as a new class of therapeutics. Herein, N-benzylanilines were found as novel allosteric activators of ALDH2 by computational virtual screening using ligand-based and structure-based screening parallel screening strategy. Then a structural optimization was performed and has led to the discovery of the compound C6. It has good activity in vitro and in vivo, which could reduce infarct size by ∼70% in ischemic stroke rat models. This study provided good lead compounds for the further development of ALDH2 activators.
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Affiliation(s)
- Wei Tian
- School of Pharmacy, Second Military Medical University, Shanghai, 200433, China; General Hospital Of Central Theater Commond, Wuhan, Hubei, 430070, China
| | - Jiapeng Guo
- School of Pharmacy, Second Military Medical University, Shanghai, 200433, China
| | - Qingsen Zhang
- School of Pharmacy, Second Military Medical University, Shanghai, 200433, China
| | - Shaoyu Fang
- School of Pharmacy, Second Military Medical University, Shanghai, 200433, China
| | - Ruolan Zhou
- School of Pharmacy, Second Military Medical University, Shanghai, 200433, China
| | - Jian Hu
- School of Pharmacy, Second Military Medical University, Shanghai, 200433, China
| | - Mingping Wang
- School of Pharmacy, Second Military Medical University, Shanghai, 200433, China
| | - Yuefan Zhang
- School of Medicine, Shanghai University, Shanghai, 20444, China
| | - Jin-Min Guo
- 960 Hospital of the Joint Logistics Support Force, Jinan, Shandong, 250031, China
| | - Zhuo Chen
- School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China
| | - Ju Zhu
- School of Pharmacy, Second Military Medical University, Shanghai, 200433, China
| | - Canhui Zheng
- School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
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Joo Kang S, Shin CM, Sung J, Kim N. Association Between ALDH2 Polymorphism and Gastric Cancer Risk in Terms of Alcohol Consumption: A Meta-Analysis. Alcohol Clin Exp Res 2020; 45:6-14. [PMID: 33170513 DOI: 10.1111/acer.14508] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Accepted: 11/02/2020] [Indexed: 01/19/2023]
Abstract
BACKGROUND Alcohol may increase gastric cancer risk. Alcohol can be more carcinogenic in persons who possess inactive ALDH2. The aim of this meta-analysis was to evaluate whether ALDH2 polymorphism can affect alcohol-induced gastric carcinogenesis. METHODS We searched the PubMed, EMBASE, and Cochrane databases to identify relevant articles published between January 2000 and September 2019. Eligible articles were selected according to inclusion and exclusion criteria. The data were analyzed using Review Manager 5.3. RESULTS A total of 7 case-control studies on ALDH2 rs671 polymorphism consisting of 3,251 gastric cancer cases and 4,943 controls were included in the analysis. Inactive ALDH2 genotypes (G/A or A/A) were associated with an increased risk of gastric cancer (odds ratio [OR] = 1.26, 95% confidence interval [CI]: 1.04 to 1.52, p = 0.02, I2 = 64%), compared with active ALDH2 (G/G genotype). Subgroup analysis by alcohol consumption showed that inactive ALDH2 increased risk for gastric cancer in moderate to heavy drinkers (OR = 1.85, 95% CI: 1.52 to 2.25, p < 0.01, I2 = 6%) more than in nondrinkers or mild drinkers (OR = 1.19; 95% CI: 1.05 to 1.36, p < 0.01, I2 = 6%). Moderate/heavy alcohol consumption increased gastric cancer risk in individuals with inactive ALDH2 (OR = 2.23, 95% CI: 1.63 to 3.05, p < 0.01, I2 = 30%) more than those with active ALDH2 (OR = 1.40, 95% CI: 0.98 to 2.01, p = 0.07, I2 = 85%). CONCLUSIONS The ALDH2 polymorphism modifies the risk of gastric cancer. Moderate/heavy drinkers are more susceptible to gastric cancer than non-drinkers or light drinkers with inactive ALDH2.
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Affiliation(s)
- Seung Joo Kang
- From the, Department of Internal Medicine, (SJK), Seoul National University Hospital Healthcare System Gangnam Center, Seoul, South Korea
| | - Cheol Min Shin
- Department of Internal Medicine, (CMS, NK), Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
| | - Joohon Sung
- School of Public Health and Institute of Health and Environment, (JS), Seoul National University, Seoul, Korea
| | - Nayoung Kim
- Department of Internal Medicine, (CMS, NK), Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea.,Department of Internal Medicine and Liver Research Institute, (NK), Seoul National University College of Medicine, Seoul, Korea
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Inoue M, Shimizu Y, Ishikawa M, Abiko S, Shimoda Y, Tanaka I, Kinowaki S, Ono M, Yamamoto K, Ono S, Sakamoto N. Relationships of early esophageal cancer with human papillomavirus and alcohol metabolism. World J Gastroenterol 2020; 26:6047-6056. [PMID: 33132654 PMCID: PMC7584065 DOI: 10.3748/wjg.v26.i39.6047] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 08/13/2020] [Accepted: 09/25/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND It is well known that an alcohol consumption habit together with inactive heterozygous aldehyde dehydrogenase-2 (ALDH2) is an important risk factor for the development of esophageal squamous cell carcinoma (ESCC). It remains controversial whether human papillomavirus (HPV) infection contributes to the occurrence/development of ESCC. There has been no study in which the relationship between ESCC and HPV in addition to alcohol dehydrogenase-1B (ADH1B) and ALDH2 genotypes was evaluated.
AIM To evaluate relationships between HPV infection and development of esophageal cancer, particularly early esophageal cancer, based on ADH1B/ALDH2 polymorphisms.
METHODS We conducted an exploratory retrospective study using new specimens, and we enrolled 145 patients who underwent endoscopic resection for superficial ESCC and had been observed for more than two years by both physical examination and endoscopic examination in Hokkaido University Hospital. Saliva was collected to analyze genetic polymorphisms of ADH1B/ALDH2. We performed in situ hybridization for resected specimens to detect HPV by using an HPV type 16/18 probe.
RESULTS HPV was detected in 15 (10.3%) of the 145 patients with ESCC. HPV-positive rates in inactive ALDH2*1/*2 and ALDH2*1/*1 + *2/*2 were 10.8% and 9.8%, respectively (P = 1.00). HPV-positive rates in slow-metabolizing ADH1B*1/*1 and ADH1B*1/*2 + *2/*2 were 12.0% and 10.0%, respectively (P = 0.72). HPV-positive rates in the heavy or moderate alcohol consumption group and the light or rare consumption group were 11.1% and 8.7%, respectively (P = 0.68). HPV-positive rates in the heavy smoking group and the light or no smoking group were 11.8% and 8.3%, respectively (P = 0.59). The 3-year incidence rates of secondary ESCC or head and neck cancer after initial treatment in the HPV-positive and HPV-negative groups were 14.4% and 21.4% (P = 0.22), respectively.
CONCLUSION In the present situation, HPV status is considered to be less important than other risk factors, such as alcohol consumption, smoking habit, ADH1B/ALDH2 polymorphisms, and HPV status would therefore have no effect on ESCC risk management.
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Affiliation(s)
- Masaki Inoue
- Department of Gastroenterology and Hepatology, Graduate School of Medicine and Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido 060-0808, Japan
| | - Yuichi Shimizu
- Division of Endoscopy, Hokkaido University Hospital, Sapporo, Hokkaido 060-8648, Japan
| | - Marin Ishikawa
- Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-0808, Japan
- Department of Gastroenterology, Hokkaido University Hospital, Sapporo, Hokkaido 060-8648, Japan
| | - Satoshi Abiko
- Department of Gastroenterology and Hepatology, Hakodate Municipal Hospital, Hakodate, Hokkaido 041-8680, Japan
| | - Yoshihiko Shimoda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine and Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido 060-0808, Japan
| | - Ikko Tanaka
- Department of Gastroenterology and Hepatology, Graduate School of Medicine and Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido 060-0808, Japan
| | - Sayoko Kinowaki
- Department of Gastroenterology and Hepatology, Graduate School of Medicine and Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido 060-0808, Japan
| | - Masayoshi Ono
- Division of Endoscopy, Hokkaido University Hospital, Sapporo, Hokkaido 060-8648, Japan
| | - Keiko Yamamoto
- Division of Endoscopy, Hokkaido University Hospital, Sapporo, Hokkaido 060-8648, Japan
| | - Shoko Ono
- Department of Gastroenterology, Hokkaido University Hospital, Sapporo, Hokkaido 060-8648, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine and Faculty of Medicine, Hokkaido University, Sapporo, Hokkaido 060-0808, Japan
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Hoshino I, Nabeya Y, Takiguchi N, Gunji H, Ishige F, Iwatate Y, Kuwajima A, Shiratori F, Okada R, Shimada H. Inducing multiple antibodies to treat squamous cell esophageal carcinoma. BMC Cancer 2020; 20:1007. [PMID: 33069225 PMCID: PMC7568359 DOI: 10.1186/s12885-020-07466-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Accepted: 09/28/2020] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND The positive response and the clinical usefulness of 14 serum antibodies in patients with esophageal squamous cell carcinoma (ESCC) were examined in this study. The Cancer Genome Atlas (TCGA) was used to investigate the frequency of gene expressions, mutations, and amplification of these 14 antigens and also the possible effects of antibody induction. METHODS Blood serum derived from 85 patients with ESCC was collected and analyzed for the 14 antibodies using ELISA. The prognosis between positive and negative antibodies were then compared. The antibody panel included LGALS1, HCA25a, HCC-22-5, and HSP70. RESULTS Patient serum was positive for all antibodies, except VEGF, with the positive rates ranging from 1.18 to 10.59%. Positive rates for LGALS1, HCA25a, HCC-22-5, and HSP70 were > 10%. TCGA data revealed that all antigen-related genes had little or no mutation or amplification, and hence an increase in gene expression affected antibody induction. The positive results from the panel accounted for the positive rate comparable to the combination of CEA and SCC. No significant association was observed between the presence of antibodies and disease prognosis. CONCLUSIONS The detection rates of LGALS1, HCA25a, HCC-22-5, and HSP70 were 10% higher in patients with ESCC. Gene overexpression may be involved in such antibody production. These four antibodies were applied as a panel in comparison with conventional tumor markers. Moreover, it was confirmed that the combination of this panel and the conventional tumor markers significantly improved the positive rate.
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Affiliation(s)
- Isamu Hoshino
- Division of Gastroenterological Surgery, Chiba Cancer Center, 666-2 Nitonacho, Chuo-ku, Chiba, 260-8717, Japan.
| | - Yoshihiro Nabeya
- Division of Gastroenterological Surgery, Chiba Cancer Center, 666-2 Nitonacho, Chuo-ku, Chiba, 260-8717, Japan
| | - Nobuhiro Takiguchi
- Division of Gastroenterological Surgery, Chiba Cancer Center, 666-2 Nitonacho, Chuo-ku, Chiba, 260-8717, Japan
| | - Hisashi Gunji
- Division of Gastroenterological Surgery, Chiba Cancer Center, 666-2 Nitonacho, Chuo-ku, Chiba, 260-8717, Japan
| | - Fumitaka Ishige
- Department of Hepatobiliary and Pancreatic Surgery, Chiba Cancer Center, 666-2 Nitonacho, Chuo-ku, Chiba, Japan
| | - Yosuke Iwatate
- Department of Hepatobiliary and Pancreatic Surgery, Chiba Cancer Center, 666-2 Nitonacho, Chuo-ku, Chiba, Japan
| | - Akiko Kuwajima
- Medical & Biological Laboratories Co., Ltd, 4-5-3 Sakae, Naka-ku, Nagoya, 460-0008, Japan
| | - Fumiaki Shiratori
- Division of Gastroenterological Surgery, Chiba Cancer Center, 666-2 Nitonacho, Chuo-ku, Chiba, 260-8717, Japan.,Department of Gastroenterological Surgery and Clinical Oncology, Graduate School of Medicine, Toho University, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan
| | - Rei Okada
- Department of Gastroenterological Surgery and Clinical Oncology, Graduate School of Medicine, Toho University, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan
| | - Hideaki Shimada
- Department of Gastroenterological Surgery and Clinical Oncology, Graduate School of Medicine, Toho University, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan
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Zvolinskaya EY, Mamedov MN, Potievskaya VI, Ivanov SA, Kaprin AD. [Role of modified cardiovascular risk factors in development of oncologic diseases]. ACTA ACUST UNITED AC 2020; 60:110-121. [PMID: 33131482 DOI: 10.18087/cardio.2020.9.n910] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Revised: 01/20/2020] [Accepted: 01/20/2020] [Indexed: 12/24/2022]
Abstract
Cardiovascular (CVD) and oncological diseases (OD) are the main causes of death worldwide and account for a heavy burden on economy, disability and mortality in many countries. Clear understanding of the mechanisms shared by CVD and cancer is important for increasing the life span and quality of life in cancer survivors as well as for preventing comorbidities and correct instructing the patients about risk factors and lifestyle modifications. Both groups of diseases share risk factors, including smoking, obesity, diabetes mellitus, alcohol consumption, unhealthy diet, etc. Along with these factors, inflammation may play a key role as it promotes both types of diseases and accompanies obesity, diabetes mellitus, arterial hypertension, and dyslipidemia. Better understanding of the interaction between CVD and cancer will allow creating common effective diagnostic and preventive strategies and safe approaches to the treatment.
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Affiliation(s)
- E Yu Zvolinskaya
- National Medical Research Center for Therapy and Preventive Medicine of the Ministry of Healthcare, Moscow, Russia
| | - M N Mamedov
- National Medical Research Center for Therapy and Preventive Medicine of the Ministry of Healthcare, Moscow, Russia
| | - V I Potievskaya
- National Medical Radiology Research Center of the Ministry of Healthcare, Moscow, Russia
| | - S A Ivanov
- Medical Radiological Research Center the branch of National Medical Radiology Research Center of the Ministry of Healthcare, Obninsk, Russia
| | - A D Kaprin
- National Medical Radiology Research Center of the Ministry of Healthcare, Moscow, Russia
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35
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Ohlsson-Nevo E, Ahlgren J, Karlsson J. Impact of health-related stigma on psychosocial functioning in cancer patients: Construct validity of the stigma-related social problems scale. Eur J Cancer Care (Engl) 2020; 29:e13312. [PMID: 32865867 PMCID: PMC7757179 DOI: 10.1111/ecc.13312] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Revised: 07/06/2020] [Accepted: 08/07/2020] [Indexed: 01/03/2023]
Abstract
OBJECTIVE The aim of this study was to evaluate the validity of Stigma-related Social Problems scale (SSP) in a cancer population. MATERIALS AND METHODS The SSP was sent to 1,179 cancer patients. Mean age was 67.9 year and 43% were women. Tests of internal consistency reliability, construct validity, item-scale convergent validity, ceiling and floor effects and known-group validity were conducted. RESULTS The response rate was 62%, and the final sample comprised 728 patients. Reliability coefficients were high for both subscales (Cronbach's alpha = 0.94). Exploratory factor analyses confirmed the unidimensionality and homogeneity of the scales. Item-scale correlations for both scales indicated satisfactory item-scale convergent validity. The proportion of subjects scoring at the lowest possible score level was 26% for the Distress scale and 28% for the Avoidance scale, while ceiling effects were marginal (<1%). The proportion of missing items was low, ranging from 1.4% to 1.5%. Known-group validity tests confirmed that the scales could capture expected differences between subgroups. CONCLUSIONS The SSP scale is a feasible instrument with sound psychometric properties that is validated in a study on 728 cancer patients. The instrument can be used to identify cancer patients at risk for psychosocial disturbances and thus in need of support.
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Affiliation(s)
- Emma Ohlsson-Nevo
- Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.,Faculty of Medicine and Health, University Health Care Research Center, Örebro University, Örebro, Sweden
| | - Johan Ahlgren
- Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.,Regional Oncological Centre Uppsala-Örebro, Uppsala, Sweden
| | - Jan Karlsson
- Faculty of Medicine and Health, University Health Care Research Center, Örebro University, Örebro, Sweden
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36
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Chen Q, Li F, Gao Y, Xu G, Liang L, Xu J. Identification of Energy Metabolism Genes for the Prediction of Survival in Hepatocellular Carcinoma. Front Oncol 2020; 10:1210. [PMID: 32903581 PMCID: PMC7438573 DOI: 10.3389/fonc.2020.01210] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Accepted: 06/15/2020] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) samples were clustered into three energy metabolism-related molecular subtypes (C1, C2, and C3) with different prognosis using the gene expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). HCC energy metabolism-related molecular subtype analysis was conducted based on the 594 energy metabolism genes. Differential expression analysis yielded 576 differentially expressed genes (DEGs) among the three subtypes, which were closely related to HCC progression. Six genes were finally selected from the 576 DEGs through LASSO-Cox regression and used in constructing a six-gene signature-associated prognostic risk model, which was validated using the TCGA internal and three GEO external validation cohorts. The risk model showed that high ANLN, ENTPD2, TRIP13, PLAC8, and G6PD expression levels were associated with bad prognosis, and high expression of ADH1C was associated with a good prognosis. The validation results showed that our risk model had a high distinguishing ability of prognosis in HCC patients. The four enriched pathways of the risk model were obtained by gene set enrichment analysis (GSEA) and found to be associated with the tumorigenesis and development of HCC, including the cell cycle, Wnt signaling pathway, drug metabolism cytochrome P450, and primary bile acid biosynthesis. The risk score calculated from the established risk model in 204 samples and other clinical characteristics were used in building a nomogram with a good prognostic prediction ability (C-index = 0.746, 95% CI = 0.714–0.777). The area under the curves (AUCs) of the nomogram model in 1-, 2-, and 3-years were 0.82, 0.77, and 0.79, respectively. Then, qRT-PCR and immunohistochemistry were used to validate the mRNA expression levels of the six genes, and significant differences in mRNA and gene expression were observed among the tumor and adjacent tissues. Overall, our study divided HCC patients into three energy metabolism-related molecular subtypes with different prognosis. Then, a risk model with a good performance in prognostic prediction was built using the TCGA dataset. This model can be used as an independent prognostic evaluation index for HCC patients.
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Affiliation(s)
- Qinjunjie Chen
- Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.,Department of Hepatic Surgery, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Fengwei Li
- Department of Hepatic Surgery, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Yuzhen Gao
- Department of Molecular Diagnosis, Clinical Medical College, Yangzhou University, Jiangsu, China
| | - Gaoran Xu
- Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Leilei Liang
- Department of Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jingchao Xu
- Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
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37
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Yokoyama A, Katada C, Yokoyama T, Takizawa K, Yano T, Oda I, Shimizu Y, Nakanishi H, Koike T, Hirao M, Okada H, Yoshii T, Katagiri A, Yamanouchi T, Matsuo Y, Kawakubo H, Kobayashi N, Ishikawa H, Muto M. The Alcohol Use Disorders Identification Test and the risk of metachronous cancer after endoscopic resection of esophageal cancer. Carcinogenesis 2020; 41:1049-1056. [PMID: 32157279 DOI: 10.1093/carcin/bgaa022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 02/10/2020] [Accepted: 03/06/2020] [Indexed: 12/15/2022] Open
Abstract
Follow-up studies of Japanese patients who had undergone endoscopic resection (ER) for early esophageal squamous cell carcinoma (ESCC) have reported a high prevalence of metachronous SCC in the upper aerodigestive tract (UAT). This prospective multicenter cohort study followed up 330 Japanese patients after ER of ESCC for a median of 49.4 months. The Alcohol Use Disorders Identification Test (AUDIT) for the 12-month period prior to study registration revealed high frequencies of high-risk drinking behaviors: 84 (25.4%) subjects had AUDIT scores of ≥15 points (suspected alcohol dependence) and 121 (36.7%) subjects had AUDIT scores of 8-14 points (hazardous drinking). Seventy-four subjects were metachronously diagnosed with ESCC, and 20 subjects with head and neck SCC (HNSCC). AUDIT scores ≥15 were associated with increases in the total number of HNSCCs per 100 person-years (0.4 for 0-7, 1.2 for 8-14 and 7.1 for ≥15; P < 0.0001). AUDIT scores were progressively associated with the grade of esophageal Lugol-voiding lesions (LVLs), a predictor of field cancerization in the UAT. Both an AUDIT score of ≥15 points and the presence of multiple LVLs were independent predictors of metachronous HNSCC [multivariate hazard ratio (95% confidence interval) = 6.98 (1.31-37.09) and 3.19 (1.19-8.54), respectively]. However, a high AUDIT score was not a predictor of metachronous ESCC. In conclusion, high AUDIT scores were markedly frequent in this population and increased the risk of metachronous HNSCC. The assessment of drinking behavior using the AUDIT and the completion of interventions for alcohol problems should be incorporated into the treatment strategy of ESCC. The name of the clinical trial register and the clinical trial registration number: Japan Esophageal Cohort Study, UMIN000001676.
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Affiliation(s)
- Akira Yokoyama
- Clinical Research Unit, National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa, Japan
| | - Chikatoshi Katada
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Tetsuji Yokoyama
- Department of Health Promotion, National Institute of Public Health, Wako, Saitama, Japan
| | - Kohei Takizawa
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Shizuoka, Japan
| | - Tomonori Yano
- Department of Gastroenterology, Endoscopy Division, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
| | - Ichiro Oda
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Tokyo, Japan
| | - Yuichi Shimizu
- Department of Gastroenterology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaidō, Japan
| | - Hiroyoshi Nakanishi
- Department of Gastroenterology, Ishikawa Prefectural Central Hospital, Kanazawa, Ishikawa, Japan
| | - Tomoyuki Koike
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Motohiro Hirao
- Department of Surgery, National Hospital Organization, Osaka National Hospital, Osaka, Osaka, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Okayama, Japan
| | - Takako Yoshii
- Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan
| | - Atsushi Katagiri
- Department of Medicine, Division of Gastroenterology, Showa University Hospital, Tokyo, Tokyo, Japan
| | - Takenori Yamanouchi
- Department of Gastroenterology, Kumamoto Regional Medical Center, Kumamoto, Kumamoto, Japan
| | - Yasumasa Matsuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
| | - Hirofumi Kawakubo
- Department of Surgery, Keio University School of Medicine, Tokyo, Tokyo, Japan
| | - Nozomu Kobayashi
- Department of Gastroenterology, Tochigi Cancer Center, Utsunomiya, Tochigi, Japan
| | - Hideki Ishikawa
- Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan
| | - Manabu Muto
- Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Kyoto, Japan
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38
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Abstract
The commercial marketplace has seen a rapid increase in the number of over-the-counter charcoal-containing mouthwashes. The purpose of this systemic review was to examine the clinical and laboratory evidence supporting therapeutic claims of efficacy and safety of use of charcoal-based mouthwashes. Secondly, the product labels and information of 36 commercially marketed charcoal mouthwashes were reviewed for active ingredients. Only 8% of charcoal mouthwashes contained an active ingredient, such as cetylpyridinium chloride or chlorhexidine. There is insufficient evidence to substantiate the therapeutic and cosmetic marketing claims of charcoal-based mouthwashes, including antimicrobial activity, anti-halitosis, tooth whitening, periodontal disease control, caries reduction and tooth remineralisation, among others. Moreover, there is no available information on charcoal particulate size or abrasivity of any of these products. Dental clinicians should advise their patients to exercise caution when using over-the-counter charcoal-containing mouthwashes because of the lack of evidence supporting therapeutic or cosmetic effectiveness as well as safety.
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39
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Wu HD, Zhang JJ, Zhou BJ. The effect of metformin on esophageal cancer risk in patients with type 2 diabetes mellitus: a systematic review and meta‑analysis. Clin Transl Oncol 2020; 23:275-282. [PMID: 32507907 DOI: 10.1007/s12094-020-02415-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 05/26/2020] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Recently, numerous studies have yielded inconsistent results regarding the effect of metformin on esophageal cancer risk in type 2 diabetes mellitus patients. The purpose of this study is to systematically assess this effect using meta-analysis. METHODS We searched clinical studies on metformin and esophageal cancer risk in PubMed, Embase, and the Cochrane Library. After literature screening, a series of meta-analyses were conducted using RevMan 5.3 software. The pooled hazard ratio (HR) and the corresponding 95% confidence interval (CI) were used as the effect size. RESULTS Five eligible studies (four cohort studies and one case-control study) were included for our meta-analysis using a random-effect model. The analysis showed that metformin could not reduce esophageal cancer risk in type 2 diabetes mellitus patients (HR 0.88, 95% CI 0.60-1.28, P > 0.05). Subgroup analyses by geographic location showed that metformin significantly reduced esophageal cancer risk in Asian patients with type 2 diabetes mellitus (HR 0.59, 95% CI 0.39-0.91, P = 0.02), without heterogeneity between studies (P = 0.80 and I2 = 0%). CONCLUSIONS Overall, our systematic review and meta-analysis demonstrate that metformin does not reduce esophageal cancer risk in type 2 diabetes mellitus patients. However, a significant reduction in esophageal cancer risk in Asian populations remains to be clarified.
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Affiliation(s)
- H-D Wu
- Department of Gastrointestinal Surgery, Second Hospital of Hebei Medical University, Heping Western Road No.215, Shijiazhuang, 050000, Hebei, China
| | - J-J Zhang
- Department of General Practice, Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China
| | - B-J Zhou
- Department of Gastrointestinal Surgery, Second Hospital of Hebei Medical University, Heping Western Road No.215, Shijiazhuang, 050000, Hebei, China.
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40
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Steve M D, Lindsey B C, Byung Soo Y, Parth J P, David A J. Microbiome and Gastroesophageal Disease: Pathogenesis and Implications for Therapy. ACTA ACUST UNITED AC 2020. [DOI: 10.29328/journal.acgh.1001018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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41
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Janfaza S, Khorsand B, Nikkhah M, Zahiri J. Digging deeper into volatile organic compounds associated with cancer. Biol Methods Protoc 2019; 4:bpz014. [PMID: 32161807 PMCID: PMC6994028 DOI: 10.1093/biomethods/bpz014] [Citation(s) in RCA: 81] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Revised: 09/25/2019] [Indexed: 12/13/2022] Open
Abstract
Volatile organic compounds (VOCs), produced and emitted through the metabolism of cancer cells or the body's immune system, are considered novel cancer biomarkers for diagnostic purposes. Of late, a large number of work has been done to find a relationship between VOCs' signature of body and cancer. Cancer-related VOCs can be used to detect several types of cancers at the earlier stages which in turn provide a significantly higher chance of survival. Here we aim to provide an updated picture of cancer-related VOCs based on recent findings in this field focusing on cancer odor database.
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Affiliation(s)
- Sajjad Janfaza
- School of Engineering, University of British Columbia, Kelowna, BC, Canada
- Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Jalal Ale Ahmad Highway, Tehran 14117, Iran
| | - Babak Khorsand
- Department of Computer Engineering, Faculty of Engineering, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Maryam Nikkhah
- Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Jalal Ale Ahmad Highway, Tehran 14117, Iran
| | - Javad Zahiri
- Bioinformatics and Computational Omics Lab (BioCOOL), Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Jalal Ale Ahmad Highway, Tehran 14117, Iran
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42
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Jones LB, Kumar S, Curry AJ, Price JS, Krendelchtchikov A, Crenshaw BJ, Bell CR, Williams SD, Tolliver TA, Saldanha SN, Sims B, Matthews QL. Alcohol Exposure Impacts the Composition of HeLa-Derived Extracellular Vesicles. Biomedicines 2019; 7:biomedicines7040078. [PMID: 31574936 PMCID: PMC6966524 DOI: 10.3390/biomedicines7040078] [Citation(s) in RCA: 6] [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: 08/22/2019] [Revised: 09/11/2019] [Accepted: 09/27/2019] [Indexed: 12/11/2022] Open
Abstract
Extracellular vesicles are nanosized vesicles that are under intense investigation for their role in intercellular communication. Extracellular vesicles have begun to be examined for their role in disease protection and their role as disease biomarkers and/or vaccine agents. The goal of this study was to investigate the effects of alcohol exposure on the biogenesis and composition of extracellular vesicles derived from the cervical cancer line, HeLa. The HeLa cells were cultured in exosome-free media and were either mock-treated (control) or treated with 50 mM or 100 mM of alcohol for 24 h and 48 h. Our results demonstrated that alcohol significantly impacts HeLa cell viability and exosome biogenesis/composition. Importantly, our studies demonstrate the critical role of alcohol on HeLa cells, as well as HeLa-derived extracellular vesicle biogenesis and composition. Specifically, these results indicate that alcohol alters extracellular vesicles’ packaging of heat shock proteins and apoptotic proteins. Extracellular vesicles serve as communicators for HeLa cells, as well as biomarkers for the initiation and progression of disease.
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Affiliation(s)
- Leandra B Jones
- Microbiology Program, Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL 36104, USA.
| | - Sanjay Kumar
- Departments of Pediatrics and Cell, Developmental and Integrative Biology, Division of Neonatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
| | - Aliyah J Curry
- Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL 36104, USA.
- Center for Nanobiotechnology Research (CNBR), Alabama State University, Montgomery, AL 36104, USA.
| | - Jayde S Price
- Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL 36104, USA.
- Center for Nanobiotechnology Research (CNBR), Alabama State University, Montgomery, AL 36104, USA.
| | - Alexandre Krendelchtchikov
- Departments of Pediatrics and Cell, Developmental and Integrative Biology, Division of Neonatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
| | - Brennetta J Crenshaw
- Microbiology Program, Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL 36104, USA.
| | - Courtnee' R Bell
- Microbiology Program, Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL 36104, USA.
| | - Sparkle D Williams
- Departments of Pediatrics and Cell, Developmental and Integrative Biology, Division of Neonatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
| | - Tambre A Tolliver
- Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL 36104, USA.
| | - Sabita N Saldanha
- Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL 36104, USA.
| | - Brian Sims
- Departments of Pediatrics and Cell, Developmental and Integrative Biology, Division of Neonatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
| | - Qiana L Matthews
- Microbiology Program, Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL 36104, USA.
- Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL 36104, USA.
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43
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Genomic characterization of early-stage esophageal squamous cell carcinoma in a Japanese population. Oncotarget 2019; 10:4139-4148. [PMID: 31289612 PMCID: PMC6609253 DOI: 10.18632/oncotarget.27014] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2018] [Accepted: 05/26/2019] [Indexed: 01/08/2023] Open
Abstract
Major risk factors for esophageal squamous cell carcinoma (ESCC) are smoking, alcohol consumption, and single nucleotide polymorphisms in ADH1B and ALDH2. Several groups have reported large-scale genomic analyses of ESCCs. However, the specific genetic changes that promote the development of ESCC have not been characterized. We performed exome sequencing of 16 fresh esophageal squamous cell neoplasms and targeted sequencing of 128 genes in 52 archival specimens, of which 26 were cancerous, and 26 were adjacent normal tissue, from Japanese ESCC patients. We found significantly more somatic mutations in TP53 and NOTCH1, CDKN2A deletions, and CCND1 amplifications in cancerous areas than in non-cancerous areas, consistent with previous studies that have characterized them as tumor suppressors and oncogenes. These data suggest that mutations, deletions, and amplifications, which alter the function of TP53, NOTCH1, CDKN2A, and CCND1, are the key changes that promote the transformation of esophageal mucosa to ESCC.
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44
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Chen X, Yu J, Tian H, Shan Z, Liu W, Pan Z, Ren J. Circle RNA hsa_circRNA_100290 serves as a ceRNA for miR-378a to regulate oral squamous cell carcinoma cells growth via Glucose transporter-1 (GLUT1) and glycolysis. J Cell Physiol 2019; 234:19130-19140. [PMID: 31187488 DOI: 10.1002/jcp.28692] [Citation(s) in RCA: 93] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 02/20/2019] [Accepted: 03/21/2019] [Indexed: 12/30/2022]
Abstract
Aerobic glycolysis (the Warburg effect) is a robust metabolic hallmark of most tumors, including oral squamous cell carcinoma (OSCC). Glucose transporter 1 (GLUT1), a major glucose transporter regulating the glucose uptake, is upregulated in OSCC and participated in the cell glycolysis of OSCC. The deregulation and function of noncoding RNAs in cancers have been widely reported. Reportedly, hsa_circular RNA (circRNA)_100290 (circ_SLC30A7) is significantly upregulated (fold change = 6.91, p < 0.0000001) in OSCC. According to online tools prediction (miRWalk, miRanda, and Targetscan), miR-378a could simultaneously target circRNA_100290 and GLUT1. Herein, the expression of circRNA_100290 and GLUT1 remarkably increased in oral tumor tissue specimens and cells. In OSCC cell lines, cell proliferation and glycolysis could be remarkably downregulated by circRNA_100290 silence, which could be rescued by GLUT1 overexpression. Conversely, miR-378a expression could be remarkably inhibited in tumor tissue specimens and cells. The effect of miR-378a overexpression on OSCC cells was similar to those of circRNA_100290 silence. miR-378a directly bound to circRNA_100290 and GLUT1 3'-untranslated region, circRNA_100290 could remarkably relieve miR-378a-induced inhibition on GLUT1 via acting as a competing endogenous RNA (ceRNA). miR-378a inhibition remarkably attenuated the effect of circRNA_100290 silence on cell proliferation and glycolysis in OSCC cell lines. In summary, circRNA_100290 serves as a ceRNA to counteract miR-378a-mediated GLUT1 suppression, thus promoting glycolysis and cell proliferation in OSCC. We provide a reliable experimental basis for understanding the mechanism of cell growth and glycolysis deregulation in OSCC.
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Affiliation(s)
- Xing Chen
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.,Department of Head and Neck Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Jianjun Yu
- Department of Head and Neck Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Hao Tian
- Department of Head and Neck Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Zhenfeng Shan
- Department of Head and Neck Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Wei Liu
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zhen Pan
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Jihao Ren
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
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Chen WC, Bye H, Matejcic M, Amar A, Govender D, Khew YW, Beynon V, Kerr R, Singh E, Prescott NJ, Lewis CM, Babb de Villiers C, Parker MI, Mathew CG. Association of genetic variants in CHEK2 with oesophageal squamous cell carcinoma in the South African Black population. Carcinogenesis 2019; 40:513-520. [PMID: 30753320 PMCID: PMC6556703 DOI: 10.1093/carcin/bgz026] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Revised: 12/18/2018] [Accepted: 02/07/2019] [Indexed: 12/15/2022] Open
Abstract
Oesophageal squamous cell carcinoma (OSCC) has a high incidence in southern Africa and a poor prognosis. Limited information is available on the contribution of genetic variants in susceptibility to OSCC in this region. However, recent genome-wide association studies have identified multiple susceptibility loci in Asian and European populations. In this study, we investigated genetic variants from seven OSCC risk loci identified in non-African populations for association with OSCC in the South African Black population. We performed association studies in a total of 1471 cases and 1791 controls from two study sample groups, which included 591 cases and 852 controls from the Western Cape and 880 cases and 939 controls from the Johannesburg region in the Gauteng province. Thereafter, we performed a meta-analysis for 11 variants which had been genotyped in both studies. A single nucleotide polymorphism in the CHEK2 gene, rs1033667, was significantly associated with OSCC [P = 0.002; odds ratio (OR) = 1.176; 95% confidence interval (CI): 1.06-1.30]. However, single nucleotide polymorphisms in the CASP8/ALS2CR12, TMEM173, PLCE1, ALDH2, ATP1B2/TP53 and RUNX1 loci were not associated with the disease (P > 0.05). The lack of association of six of these loci with OSCC in South African populations may reflect different genetic risk factors in non-African and African populations or differences in the genetic architecture of African genomes. The association at CHEK2, a gene with key roles in cell cycle regulation and DNA repair, in an African population provides further support for the contribution of common genetic variants at this locus to the risk of oesophageal cancer.
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Affiliation(s)
- Wenlong C Chen
- National Cancer Registry, National Health Laboratory Service, Johannesburg, South Africa
- Sydney Brenner Institute for Molecular Bioscience, University of the Witwatersrand, Johannesburg, South Africa
- Division of Human Genetics, School of Pathology, National Health Laboratory Service and University of the Witwatersrand, Johannesburg, South Africa
| | - Hannah Bye
- Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, King’s College London, London, United Kingdom
| | - Marco Matejcic
- Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Ariella Amar
- Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, King’s College London, London, United Kingdom
| | - Dhiren Govender
- Division of Anatomical Pathology, University of Cape Town, Cape Town, South Africa
| | - Yee Wen Khew
- Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, King’s College London, London, United Kingdom
| | - Victoria Beynon
- Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, King’s College London, London, United Kingdom
| | - Robyn Kerr
- Division of Human Genetics, School of Pathology, National Health Laboratory Service and University of the Witwatersrand, Johannesburg, South Africa
| | - Elvira Singh
- National Cancer Registry, National Health Laboratory Service, Johannesburg, South Africa
- School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Natalie J Prescott
- Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, King’s College London, London, United Kingdom
| | - Cathryn M Lewis
- Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, King’s College London, London, United Kingdom
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom
| | - Chantal Babb de Villiers
- Division of Human Genetics, School of Pathology, National Health Laboratory Service and University of the Witwatersrand, Johannesburg, South Africa
| | - M Iqbal Parker
- Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
| | - Christopher G Mathew
- Sydney Brenner Institute for Molecular Bioscience, University of the Witwatersrand, Johannesburg, South Africa
- Division of Human Genetics, School of Pathology, National Health Laboratory Service and University of the Witwatersrand, Johannesburg, South Africa
- Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, King’s College London, London, United Kingdom
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Yokoyama A, Yokoyama T, Omori T, Maesato H, Takimura T, Iwahara C, Kimura M, Matsui T, Mizukami T, Maruyama K. Endoscopic screening using esophageal iodine staining and genotypes of ADH1B and ALDH2 in Japanese alcohol-dependent women. PLoS One 2019; 14:e0210546. [PMID: 30629674 PMCID: PMC6328133 DOI: 10.1371/journal.pone.0210546] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Accepted: 12/27/2018] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND The presence of large or multiple esophageal distinct iodine-unstained lesions (DIULs) is a strong predictor of field cancerization in the upper aerodigestive tract. Several risk factors for DIULs, including genetic polymorphisms of alcohol and aldehyde dehydrogenases (ADH1B, rs1229984; ALDH2, rs671), have been demonstrated in Japanese alcohol-dependent men. However, few evaluations of alcohol-dependent women have been conducted in this field. METHODS Using multiple logistic regression models, we investigated the results of screening using esophageal iodine staining and the identification of determinants for esophageal DIULs in 472 Japanese alcohol-dependent women. RESULTS DIULs ≥5 mm, multiple DILUs, and both characteristics were observed in 35 (7.4%), 31 (6.6%), and 16 (3.4%) patients, respectively. DIULs ≥5 mm were histologically diagnosed as low-grade intraepithelial neoplasia in 26 patients and superficial squamous cell carcinoma in 9 patients. Although the inactive heterozygous ALDH2*1/*2 genotype was more common (33.3% vs. 11.4%, p = 0.002) in the group with DIULs ≥5 mm than in the group without DIULs ≥5 mm, no significant differences in the results of a questionnaire asking about current and past facial flushing after a glass of beer were seen between the groups with and without DIULs ≥5 mm. When individuals with current or former flushing were assumed to have inactive ALDH2, the sensitivity and specificity of current or former flushing to identify the presence of inactive ALDH2 were 50.0% and 93.5%, respectively; these values were previously reported to be 88% and 92%, respectively, in a Japanese general female population. The low sensitivity in the present study suggests that a lack of alcohol flushing may play a crucial role in the development of alcohol dependence in women with inactive ALDH2. No significant differences in age, usual alcohol consumption, or smoking habits were observed according to ADH1B and ALDH2 genotypes. Multiple logistic regression analyses showed that the slow-metabolizing ADH1B*1/*1 genotype (odds ratio [95% confidence interval], 12.5 [4.82-32.4] and 9.89 [3.50-27.9]), the inactive heterozygous ALDH2*1/*2 genotype (2.94 [1.18-7.38] and 3.79 [1.40-10.3]), a lower body mass index per -1 kg/m2 (1.17 [1.02-1.35] and 1.38 [1.14-1.67]), and a mean corpuscular volume ≥106 fl (3.70 [1.56-8.81] and 3.27 [1.24-8.64]) increased the risk of DIULs ≥5 mm and multiple DIULs, respectively. The combination of ADH1B*1/*1 and ALDH2*1/*2 markedly increased the risk of esophageal DIULs ≥5 mm (39.3 [10.6-146]). CONCLUSIONS Japanese alcohol-dependent women shared several common risk factors for esophageal squamous cell neoplasia with alcohol-dependent men, but with considerably different magnitudes.
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Affiliation(s)
- Akira Yokoyama
- National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa, Japan
| | - Tetsuji Yokoyama
- Department of Health Promotion, National Institute of Public Health, Wako, Saitama, Japan
| | - Tai Omori
- Endoscopy Center, Kawasaki Municipal Ida Hospital, Kawasaki, Kanagawa, Japan
| | - Hitoshi Maesato
- National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa, Japan
| | - Tsuyoshi Takimura
- National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa, Japan
| | - Chie Iwahara
- National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa, Japan
| | - Mitsuru Kimura
- National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa, Japan
| | - Toshifumi Matsui
- National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa, Japan
| | - Takeshi Mizukami
- National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa, Japan
| | - Katsuya Maruyama
- National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa, Japan
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47
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Yokoyama A, Kakiuchi N, Yoshizato T, Nannya Y, Suzuki H, Takeuchi Y, Shiozawa Y, Sato Y, Aoki K, Kim SK, Fujii Y, Yoshida K, Kataoka K, Nakagawa MM, Inoue Y, Hirano T, Shiraishi Y, Chiba K, Tanaka H, Sanada M, Nishikawa Y, Amanuma Y, Ohashi S, Aoyama I, Horimatsu T, Miyamoto S, Tsunoda S, Sakai Y, Narahara M, Brown JB, Sato Y, Sawada G, Mimori K, Minamiguchi S, Haga H, Seno H, Miyano S, Makishima H, Muto M, Ogawa S. Age-related remodelling of oesophageal epithelia by mutated cancer drivers. Nature 2019; 565:312-317. [DOI: 10.1038/s41586-018-0811-x] [Citation(s) in RCA: 346] [Impact Index Per Article: 57.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Accepted: 11/22/2018] [Indexed: 12/13/2022]
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48
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Nomura F, Kanda T, Seimiya M, Satoh M, Kageyama Y, Yamashita T, Yokosuka O, Kato N, Maruyama K. Determination of serum carbohydrate-deficient transferrin by a nephelometric immunoassay for differential diagnosis of alcoholic and non-alcoholic liver diseases. Clin Chim Acta 2018; 485:181-186. [DOI: 10.1016/j.cca.2018.06.040] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2017] [Revised: 06/25/2018] [Accepted: 06/26/2018] [Indexed: 11/28/2022]
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49
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Cui Q, Peng L, Wei L, Chang J, Tan W, Luo Y, Huang X, Zhao Y, Li J, Chu J, Shao M, Zhang C, Li C, Tan W, Lin D, Wu C. Genetic variant repressing ADH1A expression confers susceptibility to esophageal squamous-cell carcinoma. Cancer Lett 2018; 421:43-50. [DOI: 10.1016/j.canlet.2017.12.020] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2017] [Revised: 11/24/2017] [Accepted: 12/12/2017] [Indexed: 12/27/2022]
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50
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Yang Y, Lu Q, Shao X, Mo B, Nie X, Liu W, Chen X, Tang Y, Deng Y, Yan J. Development Of A Three-Gene Prognostic Signature For Hepatitis B Virus Associated Hepatocellular Carcinoma Based On Integrated Transcriptomic Analysis. J Cancer 2018; 9:1989-2002. [PMID: 29896284 PMCID: PMC5995946 DOI: 10.7150/jca.23762] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Accepted: 03/14/2018] [Indexed: 02/07/2023] Open
Abstract
Integration of public genome-wide gene expression data together with Cox regression analysis is a powerful weapon to identify new prognostic gene signatures for cancer diagnosis and prognosis. Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC), however, it remains largely unknown about the specific gene prognostic signature of HBV-associated HCC. Using Robust Rank Aggreg (RRA) method to integrate seven whole genome expression datasets, we identified 82 up-regulated genes and 577 down-regulated genes in HBV-associated HCC patients. Combination of several enrichment analysis, univariate and multivariate Cox proportional hazards regression analysis, we revealed that a three-gene (SPP2, CDC37L1, and ECHDC2) prognostic signature could act as an independent prognostic indicator for HBV-associated HCC in both the discovery cohort and the internal testing cohort. Gene set enrichment analysis showed that the high-risk group with lower expression levels of the three genes was enriched in bladder cancer and cell cycle pathway, whereas the low-risk group with higher expression levels of the three genes was enriched in drug metabolism-cytochrome P450, PPAR signaling pathway, fatty acid and histidine metabolisms. This indicates that patients of HBV-associated HCC with higher expression of these three genes may preserve relatively good hepatic cellular metabolism and function, which may also protect HCC patients from persistent drug toxicity in response to various medication. Our findings suggest a three-gene prognostic model that serves as a specific prognostic signature for HBV-associated HCC.
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Affiliation(s)
- Yao Yang
- Institute of Materia Medica, College of Pharmacy, Army Medical University (Third Military Medical University), Chongqing 400038, China
| | - Qian Lu
- Center of Hepatobiliary Pancreatic Disease, Beijing Tsinghua Changgung Hospital, Beijing 102218, China
| | - Xuejun Shao
- Brigade 315th of Territorial Defense Force, Chinese People's Liberation Army Ground Force, Xishuangbanna District, Yunan 666200, China
| | - Banghui Mo
- Institute of Materia Medica, College of Pharmacy, Army Medical University (Third Military Medical University), Chongqing 400038, China
| | - Xuqiang Nie
- Institute of Materia Medica, College of Pharmacy, Army Medical University (Third Military Medical University), Chongqing 400038, China
| | - Wei Liu
- Health Physical Examination Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China
| | - Xianhua Chen
- Diagnosis and Treatment Center for Servicemen, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing 400038, China
| | - Yuan Tang
- Institute of Materia Medica, College of Pharmacy, Army Medical University (Third Military Medical University), Chongqing 400038, China
| | - Youcai Deng
- Institute of Materia Medica, College of Pharmacy, Army Medical University (Third Military Medical University), Chongqing 400038, China
| | - Jun Yan
- Center of Hepatobiliary Pancreatic Disease, Beijing Tsinghua Changgung Hospital, Beijing 102218, China
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400042, China
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