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1
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Brockmueller A, Ruiz de Porras V, Shakibaei M. Curcumin and its anti-colorectal cancer potential: From mechanisms of action to autophagy. Phytother Res 2024; 38:3525-3551. [PMID: 38699926 DOI: 10.1002/ptr.8220] [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: 01/03/2024] [Revised: 04/06/2024] [Accepted: 04/10/2024] [Indexed: 05/05/2024]
Abstract
Colorectal cancer (CRC) development and progression, one of the most common cancers globally, is supported by specific mechanisms to escape cell death despite chemotherapy, including cellular autophagy. Autophagy is an evolutionarily highly conserved degradation pathway involved in a variety of cellular processes, such as the maintenance of cellular homeostasis and clearance of foreign bodies, and its imbalance is associated with many diseases. However, the role of autophagy in CRC progression remains controversial, as it has a dual function, affecting either cell death or survival, and is associated with cellular senescence in tumor therapy. Indeed, numerous data have been presented that autophagy in cancers serves as an alternative to cell apoptosis when the latter is ineffective or in apoptosis-resistant cells, which is why it is also referred to as programmed cell death type II. Curcumin, one of the active constituents of Curcuma longa, has great potential to combat CRC by influencing various cellular signaling pathways and epigenetic regulation in a safe and cost-effective approach. This review discusses the efficacy of curcumin against CRC in vitro and in vivo, particularly its modulation of autophagy and apoptosis in various cellular pathways. While clinical studies have assessed the potential of curcumin in cancer prevention and treatment, none have specifically examined its role in autophagy. Nonetheless, we offer an overview of potential correlations to support the use of this polyphenol as a prophylactic or co-therapeutic agent in CRC.
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Affiliation(s)
- Aranka Brockmueller
- Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Vicenç Ruiz de Porras
- CARE Program, Germans Trias i Pujol Research Institute (IGTP), Barcelona, Spain
- Catalan Institute of Oncology, Badalona Applied Research Group in Oncology (B·ARGO), Barcelona, Spain
- GRET and Toxicology Unit, Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain
| | - Mehdi Shakibaei
- Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilians-University Munich, Munich, Germany
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Stasik K, Filip R. The Complex Relationship between Mechanisms Underlying Inflammatory Bowel Disease, Its Treatment, and the Risk of Lymphomas: A Comprehensive Review. Int J Mol Sci 2024; 25:4241. [PMID: 38673824 PMCID: PMC11049907 DOI: 10.3390/ijms25084241] [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: 02/25/2024] [Revised: 04/06/2024] [Accepted: 04/08/2024] [Indexed: 04/28/2024] Open
Abstract
Patients with inflammatory bowel disease may be at higher risk of developing lymphomas and other cancers of the gastrointestinal tract. In addition, there may be a link between the use of thiopurines or anti-tumor necrosis factor drugs (anti-TNF) and these pathologies. The treatment of patients with Crohn's disease who have previously been diagnosed with lymphoma is a challenge for gastroenterologists. In this report, we examine important clinical issues related to the treatment of patients with inflammatory bowel disease with active lymphoma, as well as of patients with hematological cancer history. In this discussion, we take into account most of the available treatments for inflammatory bowel disease, as well as the impact of chronic inflammation and viral infections. In addition, we try to find common ground for the development of lymphoproliferative disorders and autoimmune diseases. Patients with inflammatory bowel disease may be at higher risk of developing lymphomas and other cancers of the gastrointestinal tract. Chronic inflammatory processes and viral infections play an important role in carcinogenesis. In addition, there may be a link between the use of thiopurines or anti-TNF drugs and these pathologies. A significant risk of the development of lymphoma in people undergoing each therapy should be considered, and it should be estimated how much greater this risk will be in patients with a history of lymphoproliferative disorders. The following review is an attempt to answer which therapy would be the most appropriate for patients with Crohn's disease and a history of lymphoma treatment. A lack of clear guidelines creates great challenges for doctors.
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Affiliation(s)
- Katarzyna Stasik
- Department of Gastroenterology with IBD Unit, Clinical Hospital No. 2, 35-301 Rzeszow, Poland;
| | - Rafał Filip
- Faculty of Medicine, University of Rzeszow, 35-959 Rzeszow, Poland
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3
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Patel RK, Frankel L, Cardeiro M, Hansen W, Takabe K, Rashid OM. The Role of Crohn Disease on Breast Cancer Incidence: A Clinical Analysis. World J Oncol 2023; 14:457-463. [PMID: 38022407 PMCID: PMC10681792 DOI: 10.14740/wjon1644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Accepted: 08/26/2023] [Indexed: 12/01/2023] Open
Abstract
Background Crohn disease is a chronic inflammatory disease that can affect the entire gastrointestinal tract. The pathophysiology of this disease characteristically involves transmural inflammation, which predisposes patients to various gastrointestinal cancers such as colon cancer. Although the increased risk of gastrointestinal cancers in Crohn disease has been well established, the risk of extra-gastrointestinal cancers remains unknown. We sought to study the risk of breast cancer in patients with Crohn disease. Methods The data for this retrospective study were compiled using the International Classification of Disease Ninth Revision (ICD-9) and ICD 10th Revision (ICD-10) codes from the national Health Insurance Portability and Accountability Act (HIPAA)-compliant PearlDiver database from 2010 to 2019. Patients were matched for age, sex, and Charlson Comorbidity Index (CCI). Statistical analyses were implemented to assess Chi-squared, logistic regression, and odds ratio. Results The database query resulted in 70,027 patients in both the control and Crohn disease groups. The incidence of breast cancer was 4,087 in the control group compared to 654 in the Crohn disease group. The P value was < 2.2 × 10-16 and the odds ratio was 0.15 (95% confidence interval (CI)). Patients without Crohn disease had an increased prevalence of breast cancer throughout all age ranges compared to patients with Crohn disease. Additionally, patients without Crohn disease had higher rates of breast cancer throughout the four major regions of the United States. In terms of healthcare costs, patients with breast cancer and a history of Crohn disease paid $23.87 more per hospital visit compared to patients with breast cancer and no history of Crohn disease. Conclusions The results of this study indicate a statistically significant correlation between Crohn disease and a reduced incidence of breast cancer. This finding is true across all age groups and across the United States. Further study is required to investigate a possible mechanism between the pathophysiology of Crohn disease ultimately leading to reduced tumorigenesis in the breast.
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Affiliation(s)
- Raina K. Patel
- Nova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine, Fort Lauderdale, FL, USA
| | - Lexi Frankel
- Nova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine, Fort Lauderdale, FL, USA
| | - Matthew Cardeiro
- Nova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine, Fort Lauderdale, FL, USA
| | - Wade Hansen
- Nova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine, Fort Lauderdale, FL, USA
| | - Kazuaki Takabe
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
- Department of Surgery, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, The State University of New York, Buffalo, NY, USA
| | - Omar M. Rashid
- Nova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine, Fort Lauderdale, FL, USA
- Michael and Dianne Bienes Comprehensive Cancer Center, Holy Cross Health, Fort Lauderdale, FL, USA
- University of Miami Leonard M. School of Medicine, Miami, FL, USA
- Massachusetts General Hospital, Boston, MA, USA
- Broward Health, Fort Lauderdale, FL, USA
- Topline MD Alliance, FL, USA
- Memorial Health, Pembroke Pines, FL, USA
- Delray Medical Center, Delray, FL, USA
- Complex General Surgical Oncology, General and Robotic Surgery, TopLine MD Alliance, Fort Lauderdale, FL 33308, USA
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Ventelä J, Alanko A, Auvinen A, Lohi O, Nikkilä A. Dual direction associations between common autoimmune diseases and leukemia among children and young adults: A systematic review. Cancer Epidemiol 2023; 86:102411. [PMID: 37423102 DOI: 10.1016/j.canep.2023.102411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 06/28/2023] [Accepted: 06/29/2023] [Indexed: 07/11/2023]
Abstract
BACKGROUND Childhood leukemia and many autoimmune (AI) diseases are severe pediatric conditions with lifelong consequences. AI diseases form a heterogeneous disease group affecting about 5 % of children worldwide, while leukemia is the most common malignancy among children aged 0-14 years. The timing and similarities in suggested inflammatory and infectious triggers of AI disease and leukemia have raised a question whether the diseases share common etiological origins. We conducted a systematic review to evaluate the evidence linking childhood leukemia and AI diseases. DATA SOURCES In the systematic literature search CINAHL (from 1970), Cochrane Library (form 1981), PubMed (from 1926) and Scopus (from 1948) were queried in June 2023. REVIEW METHODS We included studies covering the association between any AI disease and acute leukemia, limiting it to children and adolescents under 25 years old. The studies were reviewed independently by two researchers and the risk of bias was assessed. RESULTS A total of 2119 articles were screened and 253 studies were selected for detailed evaluation. Nine studies met the inclusion criteria, of which eight were cohort studies and one was a systematic review. The diseases covered were type 1 diabetes mellitus, inflammatory bowel diseases and juvenile arthritis alongside acute leukemia. Five cohort studies were suitable for more detailed analysis: a rate ratio for leukemia diagnosis after any AI disease was 2.46 (95 % CI 1.17-5.18; heterogeneity I2 15 %) with a random-effects model. CONCLUSIONS The results of this systematic review indicate that AI diseases in childhood are associated with a moderately increased risk of leukemia. The association for individual AI diseases needs further investigation.
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Affiliation(s)
- Julia Ventelä
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
| | - Anni Alanko
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Anssi Auvinen
- Faculty of Social Sciences, Tampere University and Tampere University Hospital, Tampere, Finland
| | - Olli Lohi
- Tampere Center for Child, Adolescent, Maternal Health Research and Tays Cancer Center, Tampere University and Tampere University Hospital, Tampere, Finland
| | - Atte Nikkilä
- Tampere Center for Child, Adolescent, Maternal Health Research and Tays Cancer Center, Tampere University and Tampere University Hospital, Tampere, Finland
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5
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Massano A, Bertin L, Zingone F, Buda A, Visaggi P, Bertani L, de Bortoli N, Fassan M, Scarpa M, Ruffolo C, Angriman I, Bezzio C, Casini V, Ribaldone DG, Savarino EV, Barberio B. Extraintestinal Cancers in Inflammatory Bowel Disease: A Literature Review. Cancers (Basel) 2023; 15:3824. [PMID: 37568640 PMCID: PMC10417189 DOI: 10.3390/cancers15153824] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 07/24/2023] [Accepted: 07/25/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a group of chronic multifactorial inflammatory disorders including two major entities: Crohn's disease (CD) and ulcerative colitis (UC). Preliminary evidence suggests that patients with IBD may be at increased risk of developing intestinal and extraintestinal cancers (EICs). Actually, little is known about the association between IBD and EICs, and there is ever-growing concern regarding the safety of immunomodulators and biological therapy, which may represent a risk factor for carcinogenesis. AIMS The aim of this review is to summarize the evidence regarding the association between IBD and EICs, the safety of immunomodulators and biological therapy and the management of immunomodulators and biologic agents in IBD patients with prior or current EICs. RESULTS IBD patients have a higher risk of developing different forms of extraintestinal solid organ tumors and hematological malignancies. Immunomodulators and biological therapy may increase the risk of developing some types of EICs and may be consciously used in patients with IBD and current or prior history of malignancy. CONCLUSIONS Decisions regarding the use of immunomodulators or biological therapies should be made on an individual basis, considering a multidisciplinary approach involving oncologists.
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Affiliation(s)
- Alessandro Massano
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (A.M.); (L.B.); (F.Z.); (B.B.)
| | - Luisa Bertin
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (A.M.); (L.B.); (F.Z.); (B.B.)
| | - Fabiana Zingone
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (A.M.); (L.B.); (F.Z.); (B.B.)
| | - Andrea Buda
- Gastroenterology Unit, Department of Gastrointestinal Oncological Surgery, S. Maria del Prato Hospital, 32032 Feltre, Italy;
| | - Pierfrancesco Visaggi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; (P.V.); (L.B.); (N.d.B.)
| | - Lorenzo Bertani
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; (P.V.); (L.B.); (N.d.B.)
| | - Nicola de Bortoli
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; (P.V.); (L.B.); (N.d.B.)
| | - Matteo Fassan
- Surgical Pathology Unit, Department of Medicine, University of Padova, 35138 Padova, Italy;
| | - Marco Scarpa
- General Surgery Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35138 Padova, Italy; (M.S.); (C.R.); (I.A.)
| | - Cesare Ruffolo
- General Surgery Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35138 Padova, Italy; (M.S.); (C.R.); (I.A.)
| | - Imerio Angriman
- General Surgery Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35138 Padova, Italy; (M.S.); (C.R.); (I.A.)
| | - Cristina Bezzio
- IBD Center, Gastroenterology Unit, Rho Hospital, ASST Rhodense, 20017 Rho, Italy;
| | | | - Davide Giuseppe Ribaldone
- Department of Medical Sciences, Division of Gastroenterology, University of Turin, 10126 Turin, Italy;
| | - Edoardo Vincenzo Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (A.M.); (L.B.); (F.Z.); (B.B.)
| | - Brigida Barberio
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (A.M.); (L.B.); (F.Z.); (B.B.)
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Zhou BG, Yu Q, Jiang X, Mei YZ, Ding YB, Wang M. Association between inflammatory bowel disease and risk of incident prostate cancer: a systematic review and meta-analysis of cohort studies. Int J Colorectal Dis 2023; 38:168. [PMID: 37310514 DOI: 10.1007/s00384-023-04465-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/07/2023] [Indexed: 06/14/2023]
Abstract
BACKGROUND AND OBJECTIVE Numerous observational studies have been conducted to investigate the potential association between inflammatory bowel disease (IBD) and prostate cancer (PCa). However, a definitive conclusion has yet to be established. We therefore performed a meta-analysis to explore the relationship between these two conditions. METHODS PubMed, Embase, and Web of Science databases were systematically searched to identify all relevant cohort studies that investigated the association between IBD and risk of incident PCa published from inception to February 2023. The pooled hazard ratios (HRs) with 95% confidence intervals (CI) was calculated as effect size for the outcome based on random-effects model meta-analysis. RESULTS A total of 18 cohort studies with 592,853 participants were included. The meta-analysis revealed that IBD was linked to an elevated risk of incident PCa (HR = 1.20, 95% CI: 1.06-1.37, P = 0.004). Further subgroup analyses revealed that ulcerative colitis (UC) was linked to an increased risk of incident PCa (HR = 1.20, 95% CI: 1.06-1.38, P = 0.006), while Crohn's disease (CD) is not significantly associated with a higher risk of PCa (HR = 1.03, 95% CI: 0.91-1.17, P = 0.65). There was a significant correlation between IBD and an elevated risk of incident PCa in the European population, but such a correlation was not observed in the Asian and North American populations. Sensitivity analyses indicated that our results were robust. CONCLUSIONS Our latest evidence indicates that IBD was linked to an elevated risk of incident PCa, especially in UC patients and the European population.
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Affiliation(s)
- Ben-Gang Zhou
- Dalian Medical University, Dalian, Liaoning Province, China
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368, Hanjiang Middle Road, Hanjiang District, Yangzhou, Jiangsu Province, China
| | - Qi Yu
- Department of Gastroenterology, Wuxi Xinwu District Xinrui Hospital, Wuxi, Jiangsu Province, China
| | - Xin Jiang
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368, Hanjiang Middle Road, Hanjiang District, Yangzhou, Jiangsu Province, China
| | - Yu-Zhou Mei
- Department of Gastroenterology, The People's Hospital of China Three Gorges University, Yichang, Hubei Province, China
| | - Yan-Bing Ding
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368, Hanjiang Middle Road, Hanjiang District, Yangzhou, Jiangsu Province, China.
| | - Mei Wang
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368, Hanjiang Middle Road, Hanjiang District, Yangzhou, Jiangsu Province, China.
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Podmore B, Beier D, Burisch J, Genestin E, Haeckl D, Nagel O, Qizilbash N, Schwartz DA, Vavricka SR, Bennett D, Dignass A. Malignancy rates in Crohn's disease patients with perianal fistula: A German retrospective cohort study. United European Gastroenterol J 2023. [PMID: 37140403 DOI: 10.1002/ueg2.12396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 03/30/2023] [Indexed: 05/05/2023] Open
Abstract
BACKGROUND Patients with inflammatory bowel disease are at increased risk of colorectal and extra-intestinal cancer. However, the overall cancer risk in patients with Crohn's disease (CD) with perianal fistulas (PF) (CPF) and those with CD without PF (non-PF CD) is unclear. OBJECTIVE To describe the prevalence and incidence of cancer in patients with CPF and non-PF CD, and to estimate incidence rate ratio (IRR) of cancer between CPF and non-PF CD groups. METHODS A retrospective cohort study was conducted using the German InGef (Institute for Applied Health Research Berlin) research database. Patients with a CD record and PF from 1 January 2013 to 31 December 2014 were identified and followed up from 1 January 2015 until the first occurrence of cancer, end of health insurance contributing data, death, or end of study period (31 December 2020). Prevalence of any type of cancer including patients with CD diagnosed with cancer in the selection period and incidence of cancer excluding patients with CD diagnosed with cancer in the selection period were calculated. RESULTS In total, 10,208 patients with CD were identified. Of 824 patients with CPF (8.1%), 67 had had a malignancy (6-year period crude malignancy prevalence 8.13% [95% confidence interval (CI) 6.36%-10.21%]), which was lower than patients with non-PF CD (19.8% [95% CI 19%-20.6%]). Incidence (per 100,000 person-years) in patients with CPF was 1184 (95% CI 879-1561) and in non-PF CD was 2365 (95% CI 2219-2519). There was no significant difference in the adjusted IRR of cancer for the CPF group compared with the non-PF CD group (0.83 [95% CI 0.62-1.10]; p = 0.219). CONCLUSION There was no significant difference in the incidence of any cancer in patients with CPF compared with non-PF CD. However, patients with CPF had a higher numerical risk of cancer than the general German population.
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Affiliation(s)
| | - Dominik Beier
- InGef - Institute for Applied Health Research Berlin GmbH, Berlin, Germany
| | - Johan Burisch
- Gastrounit, Medical Division, Copenhagen University Hospital, Amager and Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
| | | | - Dennis Haeckl
- WIG2 GmbH, Leipzig, Germany
- Faculty of Economics and Management Science, Leipzig University, Leipzig, Germany
| | - Oliver Nagel
- InGef - Institute for Applied Health Research Berlin GmbH, Berlin, Germany
| | | | - David A Schwartz
- Vanderbilt University Medical Center in Nashville, Nashville, Tennessee, USA
| | - Stephan R Vavricka
- Center of Gastroenterology and Hepatology, Zürich, Switzerland
- Department of Gastroenterology and Hepatology, University Hospital, Zurich, Switzerland
| | - Dimitri Bennett
- Takeda Development Center Americas, Inc., Cambridge, Massachusetts, USA
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Axel Dignass
- Department of Medicine I, Agaplesion Markus Hospital, Frankfurt, Germany
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Tichanek F, Försti A, Liska V, Hemminki A, Hemminki K. Survival in Colon, Rectal and Small Intestinal Cancers in the Nordic Countries through a Half Century. Cancers (Basel) 2023; 15:cancers15030991. [PMID: 36765946 PMCID: PMC9913304 DOI: 10.3390/cancers15030991] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 01/31/2023] [Accepted: 02/01/2023] [Indexed: 02/08/2023] Open
Abstract
Background: Survival studies in intestinal cancers have generally shown favorable development, but few studies have been able to pinpoint the timing of the changes in survival over an extended period. Here, we compared the relative survival rates for colon, rectal and small intestinal cancers from Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE). Design: Relative 1-, 5- and 5/1-year conditional survival data were obtained from the NORDCAN database for the years 1971-2020. Results: The 50-year survival patterns were country-specific. For colon and rectal cancers, the slopes of survival curves bended upwards for DK, were almost linear for NO and bended downwards for FI and SE; 5-year survival was the highest in DK. Survival in small intestinal cancer was initially below colon and rectal cancers but in FI and NO it caught up toward the end of the follow-up. Conclusions: Relative survival in intestinal cancers has developed well in the Nordic countries, and DK is an example of a country which in 20 years was able to achieve excellent survival rates in colon and rectal cancers. In the other countries, the increase in survival curves for colon and rectal cancer has slowed down, which may be a challenge posed by metastatic cancers.
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Affiliation(s)
- Filip Tichanek
- Biomedical Center, Faculty of Medicine, Charles University Pilsen, 30605 Pilsen, Czech Republic
- Institute of Pathological Physiology, Faculty of Medicine in Pilsen, Charles University, 32300 Pilsen, Czech Republic
| | - Asta Försti
- Hopp Children’s Cancer Center (KiTZ), 69120 Heidelberg, Germany
- Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), 69210 Heidelberg, Germany
| | - Vaclav Liska
- Biomedical Center, Faculty of Medicine, Charles University Pilsen, 30605 Pilsen, Czech Republic
- Department of Surgery, School of Medicine in Pilsen, University Hospital, 30605 Pilsen, Czech Republic
| | - Akseli Hemminki
- Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, 00290 Helsinki, Finland
- Comprehensive Cancer Center, Helsinki University Hospital, 00290 Helsinki, Finland
| | - Kari Hemminki
- Biomedical Center, Faculty of Medicine, Charles University Pilsen, 30605 Pilsen, Czech Republic
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
- Correspondence:
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9
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Therapeutic Management of Adults with Inflammatory Bowel Disease and Malignancies: A Clinical Challenge. Cancers (Basel) 2023; 15:cancers15020542. [PMID: 36672491 PMCID: PMC9856548 DOI: 10.3390/cancers15020542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/11/2023] [Accepted: 01/14/2023] [Indexed: 01/19/2023] Open
Abstract
Patients with chronic inflammatory bowel diseases (IBD) have increased risk of developing intestinal and extraintestinal cancers. However, once a diagnosis of malignancy is made, the therapeutic management of Crohn's disease (CD) and ulcerative colitis (UC) can be challenging as major guidelines suggest discontinuing the ongoing immunosuppressant and biological therapies for at least 2-5 years after the end of cancer treatment. Recently, new molecules such as vedolizumab and ustekinumab have been approved for IBD and limited data exist on the real risk of new or recurrent cancer in IBD patients with prior cancer, exposed to immunosuppressants and biologic agents. Thus, a multidisciplinary approach and case-by-case management is the preferred choice. The primary aim of our review was to summarize the current evidence about the safety of reintroducing an immunosuppressant or biologic agent in patients with a history of malignancy and to compare the different available therapies, including gut-selective agents. The secondary aim was to evaluate the clinical course of the IBD patients under cancer treatment who do not receive any specific immunosuppressant treatment after the diagnosis of cancer.
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10
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Güney Coşkun M, Kolay E, Basaranoglu M. Telenutrition for the management of inflammatory bowel disease: Benefits, limits, and future perspectives. World J Clin Cases 2023; 11:308-315. [PMID: 36686349 PMCID: PMC9850965 DOI: 10.12998/wjcc.v11.i2.308] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 11/24/2022] [Accepted: 12/21/2022] [Indexed: 01/12/2023] Open
Abstract
Patients with inflammatory bowel disease (IBD) require lifelong and personalized care by a multidisciplinary healthcare team. However, the traditional medical model is not ideal for patients who require continuous close monitoring and whose symptoms may dramatically worsen between regularly scheduled visits. Additionally, close dietary follow-up and monitoring of IBD in a traditional setting are challenging because of the disease complexity, high pressure on outpatient clinics with a small number of IBD specialist dietitians, and rising incidence. Given the significant burden of IBD, there is a need to develop effective dietary management strategies. The coronavirus disease 2019 pandemic caused an unprecedented shift from in-person care to delivering health care via technological remote devices. Traditional nutrition therapy and consultation can be provided by telenutrition through remote electronic communication applications that could greatly benefit patient care. Telenutrition might be useful, safe, and cost-effective compared with standard care. It is likely that virtual care for chronic diseases including IBD will continue in some form into the future. This review article summarizes the evidence about telenutrition applications in the management of IBD patients, and we gave an overview of the acceptance and impact of these interventions on health outcomes.
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Affiliation(s)
- Merve Güney Coşkun
- Department of Nutrition and Dietetics, Istanbul Medipol University, Faculty of Health Sciences, Istanbul 34810, Turkey
- Department of Nutrition and Dietetics, Institute of Health Sciences, Istanbul Medipol University, Istanbul 34810, Turkey
| | - Ezgi Kolay
- Dietitian, Independent Researcher, Istanbul 34000, Turkey
| | - Metin Basaranoglu
- Department of Gastroenterology, Bezmialem Vakif University Faculty of Medicine, Istanbul 34093, Turkey
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11
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Yuan F, Pfeiffer RM, Julián-Serrano S, Arjani S, Barrett MJ, Koshiol J, Stolzenberg-Solomon RZ. Autoimmune conditions and pancreatic cancer risk in older American adults. Int J Cancer 2023; 152:172-182. [PMID: 36059225 PMCID: PMC11260175 DOI: 10.1002/ijc.34235] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 07/20/2022] [Accepted: 07/22/2022] [Indexed: 11/07/2022]
Abstract
Pancreatic cancer (PC) is highly fatal, and its incidence is increasing in the United States. Population-based registry studies suggest associations between a few autoimmune conditions and PC risk, albeit based on a relatively small number of cases. We conducted a population-based, nested case-control study to examine the associations between autoimmune conditions and PC risk within the Surveillance, Epidemiology, and End Results Program (SEER)-Medicare population. Incident primary malignant PC cases (n = 80 074) were adults ≥66 years and diagnosed between 1992 and 2015. Controls (n = 320 296) were alive at the time cases were diagnosed and frequency-matched to cases (4:1 ratio) by age, sex, and year of diagnosis. We used multivariable-adjusted, unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 45 autoimmune conditions identified from Medicare claims. Eight autoimmune conditions including ankylosing spondylitis (OR = 1.45; 95% CI: 1.14-1.84), Graves' disease (OR = 1.18; 95% CI: 1.03-1.34), localized scleroderma (OR = 1.27; 95% CI: 1.06-1.52), pernicious anemia (OR = 1.08; 95% CI: 1.02-1.14), primary sclerosing cholangitis (OR = 1.37; 95% CI: 1.18-1.59), pure red cell aplasia (OR = 1.31; 95% CI: 1.16-1.47), type 1 diabetes (OR = 1.11; 95% CI: 1.07-1.15), and ulcerative colitis (OR = 1.18; 95% CI: 1.07-1.31) were associated with increased PC risk (false discovery rate-adjusted P values <.10). In subtype analyses, these conditions were associated with pancreatic ductal adenocarcinoma, whereas only ulcerative colitis was associated with pancreatic neuroendocrine tumors. Our results support the hypothesis that autoimmune conditions may play a role in PC development.
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Affiliation(s)
- Fangcheng Yuan
- Division Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA
| | - Ruth M Pfeiffer
- Division Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA
| | - Sachelly Julián-Serrano
- Division Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA
| | - Simran Arjani
- Division Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA
| | | | - Jill Koshiol
- Division Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA
| | - Rachael Z Stolzenberg-Solomon
- Division Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA
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12
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Gao S, Sun R, Singh R, Yu So S, Chan CTY, Savidge T, Hu M. The role of gut microbial β-glucuronidase in drug disposition and development. Drug Discov Today 2022; 27:103316. [PMID: 35820618 PMCID: PMC9717552 DOI: 10.1016/j.drudis.2022.07.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 05/27/2022] [Accepted: 07/05/2022] [Indexed: 12/15/2022]
Abstract
Gut microbial β-glucuronidase (gmGUS) is involved in the disposition of many endogenous and exogenous compounds. Preclinical studies have shown that inhibiting gmGUS activity affects drug disposition, resulting in reduced toxicity in the gastrointestinal tract (GIT) and enhanced systemic efficacy. Additionally, manipulating gmGUS activity is expected to be effective in preventing/treating local or systemic diseases. Although results from animal studies are promising, challenges remain in developing drugs by targeting gmGUS. Here, we review the role of gmGUS in host health under physiological and pathological conditions, the impact of gmGUS on the disposition of phenolic compounds, models used to study gmGUS activity, and the perspectives and challenges in developing drugs by targeting gmGUS.
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Affiliation(s)
- Song Gao
- Department of Pharmaceutical Science, College of Pharmacy and Health Sciences, Texas Southern University, 3100 Cleburne Street, Houston, TX 77004, USA.
| | - Rongjin Sun
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 4349 Martin Luther King Boulevard, Houston, TX 77204, USA
| | - Rashim Singh
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 4349 Martin Luther King Boulevard, Houston, TX 77204, USA; Sanarentero LLC, 514 N. Elder Grove Drive, Pearland, TX 77584, USA
| | - Sik Yu So
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX; Texas Children's Microbiome Center, Department of Pathology, Texas Children's Hospital, Houston, TX
| | - Clement T Y Chan
- Department of Biomedical Engineering, College of Engineering, University of North Texas, 3940 N Elm Street, Denton, TX 76207, USA; BioDiscovery Institute, University of North Texas, 1155 Union Circle #305220, Denton, TX 76203, USA
| | - Tor Savidge
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX; Texas Children's Microbiome Center, Department of Pathology, Texas Children's Hospital, Houston, TX
| | - Ming Hu
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 4349 Martin Luther King Boulevard, Houston, TX 77204, USA.
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13
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Nguyen TB, Do DN, Nguyen-Thi ML, Hoang-The H, Tran TT, Nguyen-Thanh T. Identification of potential crucial genes and key pathways shared in Inflammatory Bowel Disease and cervical cancer by machine learning and integrated bioinformatics. Comput Biol Med 2022; 149:105996. [DOI: 10.1016/j.compbiomed.2022.105996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 07/10/2022] [Accepted: 08/14/2022] [Indexed: 11/15/2022]
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14
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Immune-related biomarkers shared by inflammatory bowel disease and liver cancer. PLoS One 2022; 17:e0267358. [PMID: 35452485 PMCID: PMC9032416 DOI: 10.1371/journal.pone.0267358] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 04/04/2022] [Indexed: 12/24/2022] Open
Abstract
It has been indicated that there is an association between inflammatory bowel disease (IBD) and hepatocellular carcinoma (HCC). However, the molecular mechanism underlying the risk of developing HCC among patients with IBD is not well understood. The current study aimed to identify shared genes and potential pathways and regulators between IBD and HCC using a system biology approach. By performing the different gene expression analyses, we identified 871 common differentially expressed genes (DEGs) between IBD and HCC. Of these, 112 genes overlapped with immune genes were subjected to subsequent bioinformatics analyses. The results revealed four hub genes (CXCL2, MMP9, SPP1 and SRC) and several other key regulators including six transcription factors (FOXC1, FOXL1, GATA2, YY1, ZNF354C and TP53) and five microRNAs (miR-124-3p, miR-34a-5p, miR-1-3p, miR-7-5p and miR-99b-5p) for these disease networks. Protein-drug interaction analysis discovered the interaction of the hub genes with 46 SRC-related and 11 MMP9- related drugs that may have a therapeutic effect on IBD and HCC. In conclusion, this study sheds light on the potential connecting mechanisms of HCC and IBD.
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15
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Wang JH, D’Arcy M, Barnes EL, Freedman ND, Engels EA, Song M. Associations of Inflammatory Bowel Disease and Subsequent Cancers in a Population-Based Study of Older Adults in the United States. JNCI Cancer Spectr 2022; 6:pkab096. [PMID: 35071980 PMCID: PMC8767622 DOI: 10.1093/jncics/pkab096] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 10/08/2021] [Accepted: 10/27/2021] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Cancer risk is elevated in patients with inflammatory bowel disease (IBD). A comprehensive investigation of cancer risk in older patients (≥66 years of age) is needed, because this understudied population is at high risk. METHODS We performed a case-control study using Surveillance Epidemiology and End Results-Medicare data including 1 986 735 incident cancer cases (aged 66-99 years; diagnosed 1992-2015) and 200 000 controls matched by sex, age, race and ethnicity, and selection year. IBD was identified by ulcerative colitis (UC) or Crohn's disease (CD) diagnosis codes. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with logistic regression, adjusting for potential confounders. For colorectal cancers, we further adjusted for screening rates. We assessed confounding by medication exposure among patients with prescription drug coverage. RESULTS IBD, CD, and UC were present in 0.8%, 0.3%, and 0.5% in both cancer cases and non-cancer controls. Of 51 cancers examined, IBD was statistically significantly associated with cancers of the small intestine (OR = 2.55, 95% CI = 2.15 to 3.01), intrahepatic (OR = 1.92, 95% CI = 1.47 to 2.51) and extrahepatic bile ducts (OR = 1.75, 95% CI = 1.38 to 2.22), rectum (OR = 1.61, 95% CI = 1.36 to 1.90), and colon (OR = 1.21, 95% CI = 1.10 to 1.33). CD was associated with cancers of the small intestine (OR = 4.55, 95% CI = 3.65 to 5.67), and UC was associated with cancers of the intrahepatic bile ducts (OR = 1.87, 95% CI = 1.34 to 2.61), rectum (OR = 1.80, 95% CI = 1.47 to 2.20), and colon (OR = 1.28, 95% CI = 1.14 to 1.43). After adjusting for medication exposure, IBD was not statistically significantly associated with lung cancer, melanoma, diffuse large B-cell lymphoma, and myelodysplastic syndrome. CONCLUSIONS In this large study among older adults (≥66 years of age), IBD was positively associated with gastrointestinal cancers. Associations with extraintestinal cancers may reflect the effect of immunosuppressive medications.
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Affiliation(s)
- Jeanny H Wang
- Division of Cancer Epidemiology and Genetics, Infections and Immunoepidemiology Branch, National Cancer Institute, Rockville, MD, USA
| | - Monica D’Arcy
- Division of Cancer Epidemiology and Genetics, Biostatistics Branch, National Cancer Institute, Rockville, MD, USA
| | - Edward L Barnes
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Multidisciplinary Center for Inflammatory Bowel Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Neal D Freedman
- Division of Cancer Epidemiology and Genetics, Metabolic Epidemiology Branch, National Cancer Institute, Rockville, MD, USA
| | - Eric A Engels
- Division of Cancer Epidemiology and Genetics, Infections and Immunoepidemiology Branch, National Cancer Institute, Rockville, MD, USA
| | - Minkyo Song
- Division of Cancer Epidemiology and Genetics, Infections and Immunoepidemiology Branch, National Cancer Institute, Rockville, MD, USA
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16
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Sitar ME. Biological aging and autoimmunity. TRANSLATIONAL AUTOIMMUNITY 2022:193-203. [DOI: 10.1016/b978-0-12-824390-9.00016-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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17
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Mala A, Foteinogiannopoulou K, Koutroubakis IE. Solid extraintestinal malignancies in patients with inflammatory bowel disease. World J Gastrointest Oncol 2021; 13:1956-1980. [PMID: 35070035 PMCID: PMC8713323 DOI: 10.4251/wjgo.v13.i12.1956] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 07/06/2021] [Accepted: 08/13/2021] [Indexed: 02/06/2023] Open
Abstract
Malignancies constitute the second cause of death in patients with inflammatory bowel diseases (IBD), after cardiovascular diseases. Although it has been postulated that IBD patients are at greater risk of colorectal cancer compared to the general population, lately there has been evidence supporting that this risk is diminishing over time as a result of better surveillance, while the incidence of extraintestinal cancers (EICs) is increasing. This could be attributed either to systemic inflammation caused by IBD or to long-lasting immunosuppression due to IBD treatments. It seems that the overall risk of EICs is higher for Crohn’s disease patients and it is mainly driven by skin cancers, and liver-biliary cancers in patients with IBD and primary sclerosing cholangitis. The aims of this review were first to evaluate the prevalence, characteristics, and risk factors of EICs in patients with IBD and second to raise awareness regarding a proper surveillance program resulting in early diagnosis, better prognosis and survival, especially in the era of new IBD treatments that are on the way.
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Affiliation(s)
- Anastasia Mala
- Department of Medical Oncology, University Hospital of Heraklion, Heraklion 71110, Crete, Greece
| | | | - Ioannis E Koutroubakis
- Department of Gastroenterology, University Hospital of Heraklion, Heraklion 71110, Crete, Greece
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18
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Pan W, Zhao J, Zhang S, Chen X, Liang W, Li Q. Towards exertion of immunotherapeutics in the treatment of colorectal cancer; adverse sides, challenges, and future directions. Int Immunopharmacol 2021; 101:108337. [PMID: 34775366 DOI: 10.1016/j.intimp.2021.108337] [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] [Received: 08/02/2021] [Revised: 10/26/2021] [Accepted: 10/30/2021] [Indexed: 12/17/2022]
Abstract
Immunotherapy has growingly been prosperous as a promising therapeutic option for several kinds of solid tumors, such as colorectal cancer (CRC), subsequent to initial successful outcomes in the treatment of melanoma. The use of immunotherapy, like nivolumab and pembrolizumab (which are monoclonal antibodies against programmed cell death 1) has shown prosperous outcomes in a group of CRC patients who represent mismatch-repair-deficient and microsatellite instability-high (dMMR-MSI-H). However, a successful outcome of treatment by immune checkpoint inhibitors (ICIs) has not been observed in all of the metastatic CRC patients with dMMR-MSI-H tumors. ICIs are able to block the co-inhibitory signaling transduced in T cells, resulting in increased cytotoxic activity of T cells and efficient killing of tumor cells. In spite of availability of diverse immunotherapeutics in treatment of advanced CRC, a poor survival rate of such approaches has been reported along with challenges in the clinical practice. It is necessary to identify novel biomarkers and molecular signatures to approximate the outcome of ICI therapy in the metastatic CRC patients with dMMR-MSI-H tumors. Here we tried to clarify the current line of evidence regarding immunotherapeutics in the treatment of CRC, and discuss the challenges and hurdles in the management of these patients.
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Affiliation(s)
- Weihuo Pan
- Department of Colorectal Surgery, Shaoxing People's Hospital, The First Affiliated Hospital of Shaoxing University, Shaoxing, Zhejiang Province 312000, PR China
| | - Jianguo Zhao
- Department of Medical Oncology, Shaoxing People's Hospital, The First Affiliated Hospital of Shaoxing University, Shaoxing, Zhejiang Province 312000, PR China
| | - Songou Zhang
- College of Medicine, Shaoxing University, Shaoxing, Zhejiang 312000, PR China
| | - Xiaozhen Chen
- College of Medicine, Shaoxing University, Shaoxing, Zhejiang 312000, PR China
| | - Wenqing Liang
- Medical Research Center, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan, Zhejiang Province 316000, PR China.
| | - Qingping Li
- Department of Anaesthesiology, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan, Zhejiang Province 316000, PR China.
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19
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Elamin S, Cohen J. Telenutrition for Inflammatory Bowel Disease: A Tipping Point for Dietary Wellness. CROHNS & COLITIS 360 2021; 3:otab017. [PMID: 34485904 PMCID: PMC8394826 DOI: 10.1093/crocol/otab017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Inflammatory bowel disease (IBD), Crohn’s disease and ulcerative colitis,
cause inflammation of the digestive tract. It is estimated that about three
million Americans and, globally, over six million individuals, suffer from IBD.
While most physicians, especially gastroenterologists, are experts in the
function and pathology of the gastrointestinal tract, factors such as nutrition
science education and training, bandwidth, culture, language, and the
longitudinal nature of dietary care, represent some of the barriers to receiving
optimal nutritional guidance. Remote dietary expert counseling, an emerging
solution that has been further highlighted by the COVID-19 pandemic, can improve
IBD patients’ nutritional status, avoid food triggers, and reduce the
frequency and severity of exacerbations. Inflammatory bowel disease (IBD), Crohn’s disease and ulcerative colitis,
causes inflammation of the digestive tract. Remote nutritional expert care can
improve IBD patients’ nutritional status, avoid food triggers, and reduce
the frequency and severity of exacerbations.
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Affiliation(s)
- Sami Elamin
- Hospital Medicine Unit, Department of General Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.,Harvard Medical School, Boston, Massachusetts, USA
| | - Jonah Cohen
- Harvard Medical School, Boston, Massachusetts, USA.,Center for Advanced Endoscopy, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
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20
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Caviglia GP, Martini G, Armandi A, Rosso C, Vernero M, Bugianesi E, Astegiano M, Saracco GM, Ribaldone DG. Risk Factors of Urothelial Cancer in Inflammatory Bowel Disease. J Clin Med 2021; 10:3257. [PMID: 34362041 PMCID: PMC8347965 DOI: 10.3390/jcm10153257] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Revised: 07/22/2021] [Accepted: 07/22/2021] [Indexed: 01/31/2023] Open
Abstract
Extraintestinal cancers are important complications in patients with inflammatory bowel disease (IBD). A limited number of publications are available regarding the association between IBD and urothelial cancer. The primary outcome of our study was the comparison of the prevalence of urothelial cancer in patients with IBD with respect to the prevalence in the general population. Secondary outcomes were the assessment of risk factors for the onset of urothelial cancer in IBD. In a retrospective study we examined the medical records of all patients with a confirmed diagnosis of IBD followed in our clinic between 1978 and 2021. For each of the patients with identified urothelial cancer, more than ten patients without cancer were analyzed. Furthermore, 5739 patients with IBD were analyzed and 24 patients diagnosed with urothelial cancer were identified. The incidence of urothelial cancer, compared with the incidence in the general population, was not significantly different (0.42% vs. 0.42%; p = 0.98). Twenty-three cases were then compared (1 case was discarded due to lack of follow-up data) against 250 controls. During the multivariate analysis, smoking (odds ratio, OR = 8.15; 95% confidence interval, CI = 1.76-37.63; p = 0.007) and male sex (OR = 4.04; 95% CI = 1.29-12.66; p = 0.016) were found as risk factors. In conclusion, patients with IBD have a similar risk of developing urothelial cancer compared to the general population, but males with a history of smoking are at increased risk.
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Affiliation(s)
- Gian Paolo Caviglia
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, 10126 Torino, Italy; (G.P.C.); (G.M.); (C.R.); (E.B.); (G.M.S.)
| | - Giorgio Martini
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, 10126 Torino, Italy; (G.P.C.); (G.M.); (C.R.); (E.B.); (G.M.S.)
| | - Angelo Armandi
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, 10126 Torino, Italy; (G.P.C.); (G.M.); (C.R.); (E.B.); (G.M.S.)
| | - Chiara Rosso
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, 10126 Torino, Italy; (G.P.C.); (G.M.); (C.R.); (E.B.); (G.M.S.)
| | - Marta Vernero
- Department of Internal Medicine, San Matteo Hospital, 27100 Pavia, Italy;
| | - Elisabetta Bugianesi
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, 10126 Torino, Italy; (G.P.C.); (G.M.); (C.R.); (E.B.); (G.M.S.)
| | - Marco Astegiano
- Department of General and Specialist Medicine, Gastroenterologia-U, Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy;
| | - Giorgio Maria Saracco
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, 10126 Torino, Italy; (G.P.C.); (G.M.); (C.R.); (E.B.); (G.M.S.)
| | - Davide Giuseppe Ribaldone
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, 10126 Torino, Italy; (G.P.C.); (G.M.); (C.R.); (E.B.); (G.M.S.)
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21
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Geng Z, Geng Q. Risk of Urinary Bladder Cancer in Patients With Inflammatory Bowel Diseases: A Meta-Analysis. Front Surg 2021; 8:636791. [PMID: 34124132 PMCID: PMC8188732 DOI: 10.3389/fsurg.2021.636791] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 03/26/2021] [Indexed: 12/24/2022] Open
Abstract
A systematic search of the PubMed, Cochrane, Embase, and Web of Science databases was conducted to investigate the risk of urinary bladder cancer (BC) in patients with inflammatory bowel disease (IBD). We identified 168 articles, of which 11 met the inclusion and exclusion criteria. Our analysis included 165,176 patients with IBD, 491 of whom had BC. Overall, the pooled standardized incidence ratio (SIR) was 0.99 (95% CI: 0.87–1.12; I2 = 0%). Further subgroup analysis showed that BC risk was neither statistically higher for Crohn's disease (CD) (SIR: 1.19; 95% CI: 0.94–1.44; I2 = 0%) nor for patients with ulcerative colitis (UC) (SIR: 0.92; 95% CI: 0.77–1.06; I2 = 0%). In the analysis of two case-control studies providing data on BC in UC and CD combined, IBD patients seemed to have a higher risk of BC than non-IBD patients (relative risk: 1.25; 95% CI: 0.77–2.03; I2 = 37.5%). Although the overall risk of BC was not significantly increased among patients with IBD, there was a weak trend for the risk to be elevated in CD patients, indicating marginal significance. These findings may primarily be explained by the opposite effects of smoking on CD and UC as well as the immunosuppressive drugs these patients often take.
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Affiliation(s)
- Zhihua Geng
- Department of Orthopedics of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qing Geng
- Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China
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22
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Feng D, Yang Y, Wang Z, Wei W, Li L. Inflammatory bowel disease and risk of urinary cancers: a systematic review and pooled analysis of population-based studies. Transl Androl Urol 2021; 10:1332-1341. [PMID: 33850767 PMCID: PMC8039624 DOI: 10.21037/tau-20-1358] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Background The aim of this study is to elucidate the risk of urologic cancers in patients with Crohn’s disease (CD) and ulcerative colitis (UC). Methods Electronic databases including PubMed, the Cochrane Library, Embase and Web of Science, and manual retrieval were conducted from inception to June 2020. Two reviewers independently searched the above databases and selected the studies using prespecified standardized criteria. The Newcastle-Ottawa Scale was used to assess the risk of bias in the included studies, and this meta-analysis was completed by STATA version 14.2. Results A total of 12 cohort studies and 4 case-control studies were included in this meta-analysis. Overall, patients with inflammatory bowel disease (IBD) were at significantly increased risk of renal cancer (RCa) [standardized incidence ratio (SIR): 1.53; 95% confidence interval (CI): 1.25–1.80; I2=42.4%], but not at increased risk of prostate cancer (PCa), bladder cancer (BCa) and male genital cancer. In the subgroup analysis, CD patients had a significantly higher RCa risk (SIR: 1.95; 95% CI: 1.45–2.44; I2=39.9%). Besides, CD patients seemed to be at borderline significantly increased risks of PCa (SIR: 1.07; 95% CI: 0.93–1.20; I2=15.1%) and BCa (SIR:1.19; 95% CI: 0.94–1.44; I2=0%), and UC patients seemed to be at borderline significantly increased risks of RCa (SIR:1.31; 95% CI: 0.94–1.67; I2=48.0%) and PCa (SIR: 1.13; 95% CI: 0.93–1.33; I2=73.5%). Notably, we observed that IBD patients in Eastern countries have significantly increased PCa risk (SIR: 2.66; 95% CI: 1.52–3.81; I2=13.6%), especially for UC patients (SIR: 3.01; 95% CI: 1.75–4.27; I2=0.0%). Conclusions Our findings indicate that IBD patients with special reference to CD patients increase the risk of RCa. Besides, IBD patients in Asian countries have significantly increased risk of PCa, especially for UC patients. Further studies are warranted to elucidate the potential mechanism of RCa associated with IBD and the differences of the risk of urinary cancers between Eastern and Western countries.
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Affiliation(s)
- Dechao Feng
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.,Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
| | - Yubo Yang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Zhenghao Wang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Wuran Wei
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Li Li
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China.,Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
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23
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Zhang C, Liu S, Peng L, Wu J, Zeng X, Lu Y, Shen H, Luo D. Does inflammatory bowel disease increase the risk of lower urinary tract tumors: a meta-analysis. Transl Androl Urol 2021; 10:164-173. [PMID: 33532306 PMCID: PMC7844520 DOI: 10.21037/tau-20-1020] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Background Inflammatory bowel disease, including ulcerative colitis and Crohn’s disease, is characterized by chronic inflammation that could be a risk factor for extraintestinal cancer. The aim of this study is to evaluate whether inflammatory bowel disease is related to the risk of lower urinary tract tumors. Methods A systematical research was performed on various medical databases including PubMed, the Cochrane Library, Embase and Web of Science from inception to April 2020. Data were independently extracted by two reviewers. The Newcastle-Ottawa Scale and the Oxford Centre for Evidence-Based Medicine criteria were used to assess the quality of included articles. The analysis was completed by STATA version 14.2. Results Six hundred and twelve of records were initially identified and 16 studies were included in the final analysis. In general, inflammatory bowel disease patients were not at increased risk of prostate cancer, bladder cancer and male genital cancer. In the subgroup analysis, Crohn’s disease patients seemed to have borderline increased risk of prostate cancer [standardized incidence ratio: 1.05; 95% confidence interval (CI): 0.90–1.21; I2=15.1%] and bladder cancer (standardized incidence ratio: 1.19; 95% CI: 0.94–1.44; I2=0.0%), and ulcerative colitis patients seemed to have borderline increased risk of prostate cancer (standardized incidence ratio: 1.13; 95% CI: 0.93–1.33; I2=73.5%). Conclusions Inflammatory bowel disease did not significantly increase the risk of prostate cancer, bladder cancer and male genital cancer. Crohn’s disease patients seemed to have a higher risk of prostate cancer and bladder cancer, and ulcerative colitis patients seemed to have a higher risk of prostate cancer. ulcerative colitis patients in East Asian countries have significantly increased prostate cancer risk.
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Affiliation(s)
- Chi Zhang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Shengzhuo Liu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Liao Peng
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Jiapei Wu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Xiao Zeng
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Yiping Lu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Hong Shen
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Deyi Luo
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
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Feng D, Bai Y, Liu S, Yang Y, Han P, Wei W. Risk of renal cancer in patients with inflammatory bowel disease: A pooled analysis of population-based studies. Urol Oncol 2020; 39:93-99. [PMID: 33214029 DOI: 10.1016/j.urolonc.2020.10.078] [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: 04/23/2020] [Revised: 08/14/2020] [Accepted: 10/30/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Currently, newer epidemiological studies report the association between inflammatory bowel disease (IBD) and risk of renal cancer (RCa). Thus, we conducted a meta-analysis to determine whether IBD patients were associated with RCa risk. METHODS Various medical databases were searched from inception to April 2020. Standardized incidence ratio (SIR) or relative risk (RR) with corresponding 95% confidence intervals (CIs) were pooled. The meta-analysis was completed by STATA version 14.2. RESULTS A total of 421 articles were identified, and 11 studies met the inclusion criteria. Data from 9 cohort studies showed a significantly increased risk of RCa in IBD patients (pooled SIR: 1.53; 95%CI: 1.25-1.80; I2 = 42.4%), especially for patients with Crohn's disease (CD) (pooled SIR: 1.95; 95%CI: 1.45-2.44; I2 = 39.9%). We did not observe a significantly increased risk of RCa in patients with ulcerative colitis (UC) (pooled SIR: 1.31; 95%CI: 0.94-1.67; I2 = 48.0%) when compared to the background population. Only 2 case-control studies reported the results of RCa risk, showing no significant difference between IBD group and IBD-free group (pooled RR: 1.64; 95%CI: 0.52-5.22; I2 = 77.9%). CONCLUSIONS Our findings indicate that IBD patients with special reference to CD patients have a significantly higher risk of RCa. Further studies are warranted to enable definite conclusions to be drawn.
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Affiliation(s)
- Dechao Feng
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Yunjin Bai
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Shengzhuo Liu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Yubo Yang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Ping Han
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Wuran Wei
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.
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25
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Meyers TJ, Weiner AB, Graff RE, Desai AS, Cooley LF, Catalona WJ, Hanauer SB, Wu JD, Schaeffer EM, Abdulkadir SA, Kundu SD, Witte JS. Association between inflammatory bowel disease and prostate cancer: A large-scale, prospective, population-based study. Int J Cancer 2020; 147:2735-2742. [PMID: 32399975 DOI: 10.1002/ijc.33048] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Revised: 04/14/2020] [Accepted: 04/28/2020] [Indexed: 12/24/2022]
Abstract
Inflammatory bowel disease (IBD) is an established risk factor for colorectal cancer. Recent reports suggesting IBD is also a risk factor for prostate cancer (PC) require further investigation. We studied 218 084 men in the population-based UK Biobank cohort, aged 40 to 69 at study entry between 2006 and 2010, with follow-up through mid-2015. We assessed the association between IBD and subsequent PC using multivariable Cox regression analyses, adjusting for age at assessment, ethnic group, UK region, smoking status, alcohol drinking frequency, body mass index, Townsend Deprivation Index, family history of PC and previous prostate-specific antigen testing. Mean age at study entry was 56 years, 94% of the men were white, and 1.1% (n = 2311) had a diagnosis of IBD. After a median follow-up of 78 months, men with IBD had an increased risk of PC (adjusted hazard ratio [aHR] = 1.31, 95% confidence interval [CI] = 1.03-1.67, P = .029). The association with PC was only among men with the ulcerative colitis (UC; aHR = 1.47, 95% CI = 1.11-1.95, P = .0070), and not Crohn's disease (aHR 1.06, 95% CI = 0.63-1.80, P = .82). Results are limited by lack of data on frequency of health care interactions. In a large-scale, prospective cohort study, we detected an association between IBD, and UC specifically, with incident PC diagnosis.
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Affiliation(s)
- Travis J Meyers
- Department of Epidemiology and Biostatistics, University of California San Francisco (UCSF), San Francisco, California, USA
| | - Adam B Weiner
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Rebecca E Graff
- Department of Epidemiology and Biostatistics, University of California San Francisco (UCSF), San Francisco, California, USA
| | - Anuj S Desai
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Lauren Folgosa Cooley
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - William J Catalona
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Stephen B Hanauer
- Department of Medicine, Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Jennifer D Wu
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Edward M Schaeffer
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Sarki A Abdulkadir
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Shilajit D Kundu
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - John S Witte
- Department of Epidemiology and Biostatistics, University of California San Francisco (UCSF), San Francisco, California, USA
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26
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Bak M, Jess T, Flachs EM, Zwisler AD, Juel K, Frederiksen H. Risk of Inflammatory Bowel Disease in Patients with Chronic Myeloproliferative Neoplasms: A Danish Nationwide Cohort Study. Cancers (Basel) 2020; 12:cancers12092700. [PMID: 32967227 PMCID: PMC7564361 DOI: 10.3390/cancers12092700] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 08/14/2020] [Accepted: 08/19/2020] [Indexed: 01/18/2023] Open
Abstract
Simple Summary We wanted to investigate the risk of inflammatory bowel disease (IBD) in patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPNs), since up to 50% of these patients experience gastrointestinal symptoms and several studies have suggested an association between hematological cancers and IBD. We included ∼8000 patients and ∼80,000 sex- and age-matched, non-MPN comparisons from the general population, and found that MPN patients were two to three times more likely to develop IBD, but the absolute risk of IBD was modest. In addition, MPN patients were also 40% more likely to have a prior diagnosis of IBD. Our results pose intriguing questions about the causal pathways linking MPN and IBD, which may include genetic, treatment-related and immune-mediated factors. Moreover, it shows that abdominal symptoms in MPN patients may not only be caused by an enlarged spleen or treatment side-effects. Conversely, persistent leucocytosis and/or increased platelets in IBD patients may reflect concomitant MPN. Abstract An association between hematological cancers and inflammatory bowel disease (IBD) has previously been suggested, but the risk of IBD in patients with myeloproliferative neoplasms (MPNs) is unknown. We conducted a nationwide population-based cohort study using Danish registries, to estimate the risk of IBD in individuals diagnosed with essential thrombocythemia, polycythemia vera, myelofibrosis or unclassifiable MPN during 1994–2013. MPN patients were matched 1:10 with sex- and age-matched comparisons. Everyone was followed until a diagnosis of IBD, death/emigration, or 31 December 2013. The risk of IBD overall and according to MPN subtype was calculated using Cox regression and presented as hazard ratios (HRs) with 95% confidence intervals (CI). Of 8207 MPN patients followed for 45,232 person-years, 80 were diagnosed with IBD (61 ulcerative colitis, 19 Crohn’s disease). The rate of IBD per 1000 person-years was 1.8 (95% CI:1.4–2.2) in patients vs. 0.8 (95% CI:0.7–0.8) in comparisons, and the absolute 10-year risk of IBD was 0.8% (95% CI:0.6–1.0) in patients vs. 0.4% (95% CI:0.4–0.5) in comparisons. The HR of IBD was 2.4 (95% CI:2.1–2.9) with similar HRs for ulcerative colitis and Crohn’s disease. MPN subtype risks varied from 2.1 (95% CI:1.6–2.7) to 2.8 (95% CI:2.1–3.7). Our unselected cohort study showed a more than 2-fold increased risk of IBD in MPN patients.
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Affiliation(s)
- Marie Bak
- Department of Haematology, Zealand University Hospital, University of Copenhagen, 4000 Roskilde, Denmark
- Correspondence: ; Tel.: +45-47324894
| | - Tine Jess
- Department of Epidemiology Research, Statens Serum Institut, 2300 Copenhagen, Denmark;
| | - Esben Meulengracht Flachs
- Department of Occupational and Environmental Medicine, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen, Denmark;
| | - Ann-Dorthe Zwisler
- Danish Knowledge Centre for Rehabilitation and Palliative Care, University of Southern Denmark and Odense University Hospital, 5800 Nyborg, Denmark;
| | - Knud Juel
- National Institute of Public Health, University of Southern Denmark, 1455 Copenhagen, Denmark;
| | - Henrik Frederiksen
- Department of Haematology, Odense University Hospital, 5000 Odense, Denmark;
- Department of Clinical Epidemiology, Aarhus University Hospital, 8200 Aarhus, Denmark
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27
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Yuan F, Hung RJ, Walsh N, Zhang H, Platz EA, Wheeler W, Song L, Arslan AA, Beane Freeman LE, Bracci P, Canzian F, Du M, Gallinger S, Giles GG, Goodman PJ, Kooperberg C, Le Marchand L, Neale RE, Rosendahl J, Scelo G, Shu XO, Visvanathan K, White E, Zheng W, Albanes D, Amiano P, Andreotti G, Babic A, Bamlet WR, Berndt SI, Brennan P, Bueno-de-Mesquita B, Buring JE, Campbell PT, Chanock SJ, Fuchs CS, Gaziano JM, Goggins MG, Hackert T, Hartge P, Hassan MM, Holly EA, Hoover RN, Katzke V, Kirsten H, Kurtz RC, Lee IM, Malats N, Milne RL, Murphy N, Ng K, Oberg AL, Porta M, Rabe KG, Real FX, Rothman N, Sesso HD, Silverman DT, Thompson IM, Wactawski-Wende J, Wang X, Wentzensen N, Wilkens LR, Yu H, Zeleniuch-Jacquotte A, Shi J, Duell EJ, Amundadottir LT, Li D, Petersen GM, Wolpin BM, Risch HA, Yu K, Klein AP, Stolzenberg-Solomon R. Genome-Wide Association Study Data Reveal Genetic Susceptibility to Chronic Inflammatory Intestinal Diseases and Pancreatic Ductal Adenocarcinoma Risk. Cancer Res 2020; 80:4004-4013. [PMID: 32641412 PMCID: PMC7861352 DOI: 10.1158/0008-5472.can-20-0447] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 04/27/2020] [Accepted: 07/02/2020] [Indexed: 12/20/2022]
Abstract
Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated variants for these chronic inflammatory diseases are associated with PDAC. We examined the association between PDAC and genomic regions (±500 kb) surrounding established common susceptibility variants for ulcerative colitis, Crohn's disease, inflammatory bowel disease, celiac disease, chronic pancreatitis, and primary sclerosing cholangitis. We analyzed summary statistics from genome-wide association studies data for 8,384 cases and 11,955 controls of European descent from two large consortium studies using the summary data-based adaptive rank truncated product method to examine the overall association of combined genomic regions for each inflammatory disease group. Combined genomic susceptibility regions for ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis were associated with PDAC at P values < 0.05 (0.0040, 0.0057, 0.011, and 3.4 × 10-6, respectively). After excluding the 20 PDAC susceptibility regions (±500 kb) previously identified by GWAS, the genomic regions for ulcerative colitis, Crohn disease, and inflammatory bowel disease remained associated with PDAC (P = 0.0029, 0.0057, and 0.0098, respectively). Genomic regions for celiac disease (P = 0.22) and primary sclerosing cholangitis (P = 0.078) were not associated with PDAC. Our results support the hypothesis that genomic regions surrounding variants associated with inflammatory intestinal diseases, particularly, ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis are associated with PDAC. SIGNIFICANCE: The joint effects of common variants in genomic regions containing susceptibility loci for inflammatory bowel disease and chronic pancreatitis are associated with PDAC and may provide insights to understanding pancreatic cancer etiology.
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Affiliation(s)
- Fangcheng Yuan
- Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Rayjean J Hung
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System and University of Toronto, Toronto, Ontario, Canada
| | - Naomi Walsh
- National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin, Ireland
| | - Han Zhang
- Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland
| | - Elizabeth A Platz
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - William Wheeler
- Information Management Services, Inc., Silver Spring, Maryland
| | - Lei Song
- Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland
| | - Alan A Arslan
- Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, USA
- Department of Population Health, New York University School of Medicine, New York, New York
- Department of Environmental Medicine, New York University School of Medicine, New York, New York
- Perlmutter Cancer Center, New York University School of Medicine, New York, New York
| | | | - Paige Bracci
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California
| | - Federico Canzian
- Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Mengmeng Du
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Steven Gallinger
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System and University of Toronto, Toronto, Ontario, Canada
| | - Graham G Giles
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
| | - Phyllis J Goodman
- SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Charles Kooperberg
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Loic Le Marchand
- Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii
| | - Rachel E Neale
- Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Australia
| | - Jonas Rosendahl
- Department of Internal Medicine I, Martin Luther University, Halle, Germany
| | | | - Xiao-Ou Shu
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Kala Visvanathan
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Emily White
- Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Wei Zheng
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Demetrius Albanes
- Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland
| | - Pilar Amiano
- Public Health Division of Gipuzkoa, Ministry of Health of the Basque Government, Donostia-San Sebastian, Spain
- Biodonostia Health Research Institute, Donostia-San Sebastian, Spain
- CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain
| | | | - Ana Babic
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - William R Bamlet
- Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - Sonja I Berndt
- Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland
| | - Paul Brennan
- International Agency for Research on Cancer, Lyon, France
| | - Bas Bueno-de-Mesquita
- Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
- Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands
- Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, UK
- Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Julie E Buring
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Peter T Campbell
- Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia
| | - Stephen J Chanock
- Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland
| | - Charles S Fuchs
- Yale Cancer Center, New Haven, Connecticut
- Department of Medicine, Yale School of Medicine, New Haven, Connecticut
- Smilow Cancer Hospital, New Haven, Connecticut
| | - J Michael Gaziano
- Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
- Boston Veteran Affairs Healthcare System, Boston, Massachusetts
| | - Michael G Goggins
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Patricia Hartge
- Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland
| | - Manal M Hassan
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Elizabeth A Holly
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California
| | - Robert N Hoover
- Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland
| | - Verena Katzke
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Holger Kirsten
- Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
- LIFE-Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
| | - Robert C Kurtz
- Gastroenterology, Hepatology, and Nutrition Service, Memorial Sloan Kettering Cancer Center, New York, New York
| | - I-Min Lee
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Nuria Malats
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre, Madrid, Spain
| | - Roger L Milne
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
| | - Neil Murphy
- Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France
| | - Kimmie Ng
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - Ann L Oberg
- Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - Miquel Porta
- CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
- Hospital del Mar Institute of Medical Research (IMIM), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Kari G Rabe
- Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - Francisco X Real
- CIBERONC, Madrid, Spain
- Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre, Madrid, Spain
- Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
| | - Nathaniel Rothman
- Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland
| | - Howard D Sesso
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Debra T Silverman
- Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland
| | - Ian M Thompson
- CHRISTUS Santa Rosa Hospital - Medical Center, San Antonio, Texas
| | - Jean Wactawski-Wende
- Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, New York
| | - Xiaoliang Wang
- Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Nicolas Wentzensen
- Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland
| | - Lynne R Wilkens
- Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii
| | - Herbert Yu
- Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii
| | - Anne Zeleniuch-Jacquotte
- Department of Population Health, New York University School of Medicine, New York, New York
- Department of Environmental Medicine, New York University School of Medicine, New York, New York
- Perlmutter Cancer Center, New York University School of Medicine, New York, New York
| | - Jianxin Shi
- Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland
| | - Eric J Duell
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, Spain
| | | | - Donghui Li
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Gloria M Petersen
- Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - Brian M Wolpin
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - Harvey A Risch
- Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut
| | - Kai Yu
- Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland
| | - Alison P Klein
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland
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28
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Zhu J, Shu X, Guo X, Liu D, Bao J, Milne RL, Giles GG, Wu C, Du M, White E, Risch HA, Malats N, Duell EJ, Goodman PJ, Li D, Bracci P, Katzke V, Neale RE, Gallinger S, Van Den Eeden SK, Arslan AA, Canzian F, Kooperberg C, Beane Freeman LE, Scelo G, Visvanathan K, Haiman CA, Le Marchand L, Yu H, Petersen GM, Stolzenberg-Solomon R, Klein AP, Cai Q, Long J, Shu XO, Zheng W, Wu L. Associations between Genetically Predicted Blood Protein Biomarkers and Pancreatic Cancer Risk. Cancer Epidemiol Biomarkers Prev 2020; 29:1501-1508. [PMID: 32439797 PMCID: PMC7334065 DOI: 10.1158/1055-9965.epi-20-0091] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 03/15/2020] [Accepted: 04/27/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with few known risk factors and biomarkers. Several blood protein biomarkers have been linked to PDAC in previous studies, but these studies have assessed only a limited number of biomarkers, usually in small samples. In this study, we evaluated associations of circulating protein levels and PDAC risk using genetic instruments. METHODS To identify novel circulating protein biomarkers of PDAC, we studied 8,280 cases and 6,728 controls of European descent from the Pancreatic Cancer Cohort Consortium and the Pancreatic Cancer Case-Control Consortium, using genetic instruments of protein quantitative trait loci. RESULTS We observed associations between predicted concentrations of 38 proteins and PDAC risk at an FDR of < 0.05, including 23 of those proteins that showed an association even after Bonferroni correction. These include the protein encoded by ABO, which has been implicated as a potential target gene of PDAC risk variant. Eight of the identified proteins (LMA2L, TM11D, IP-10, ADH1B, STOM, TENC1, DOCK9, and CRBB2) were associated with PDAC risk after adjusting for previously reported PDAC risk variants (OR ranged from 0.79 to 1.52). Pathway enrichment analysis showed that the encoding genes for implicated proteins were significantly enriched in cancer-related pathways, such as STAT3 and IL15 production. CONCLUSIONS We identified 38 candidates of protein biomarkers for PDAC risk. IMPACT This study identifies novel protein biomarker candidates for PDAC, which if validated by additional studies, may contribute to the etiologic understanding of PDAC development.
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Affiliation(s)
- Jingjing Zhu
- Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii
| | - Xiang Shu
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Xingyi Guo
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Duo Liu
- Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii
- Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin, China
| | - Jiandong Bao
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Roger L Milne
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
| | - Graham G Giles
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
| | - Chong Wu
- Department of Statistics, Florida State University, Tallahassee, Florida
| | - Mengmeng Du
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Emily White
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
- Department of Epidemiology, University of Washington, Seattle, Washington
| | - Harvey A Risch
- Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut
| | - Nuria Malats
- Spanish National Cancer Research Centre (CNIO) and CIBERONC, Madrid, Spain
| | - Eric J Duell
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), L'Hospitalet de Llobregat, Spain
| | - Phyllis J Goodman
- SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Donghui Li
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Paige Bracci
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California
| | - Verena Katzke
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Rachel E Neale
- Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
| | - Steven Gallinger
- Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada
| | | | - Alan A Arslan
- Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York
| | - Federico Canzian
- Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Charles Kooperberg
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | | | - Ghislaine Scelo
- Genetic Epidemiology Group, Section of Genetics, International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Kala Visvanathan
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Christopher A Haiman
- Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - Loïc Le Marchand
- Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii
| | - Herbert Yu
- Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii
| | - Gloria M Petersen
- Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota
| | | | - Alison P Klein
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Qiuyin Cai
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Jirong Long
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Xiao-Ou Shu
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Wei Zheng
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Lang Wu
- Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii.
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Carli E, Caviglia GP, Pellicano R, Fagoonee S, Rizza S, Astegiano M, Saracco GM, Ribaldone DG. Incidence of Prostate Cancer in Inflammatory Bowel Disease: A Meta-Analysis. MEDICINA (KAUNAS, LITHUANIA) 2020; 56:285. [PMID: 32545154 PMCID: PMC7353864 DOI: 10.3390/medicina56060285] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 06/04/2020] [Accepted: 06/05/2020] [Indexed: 01/02/2023]
Abstract
Background and objectives: Inflammatory bowel disease (IBD) is associated with an increased risk of developing colorectal cancer as well as some extra-intestinal tumors, but there are still limited data about the risk of prostate cancer (PC). To analyze if there is an increased risk of PC in patients affected by IBD, we performed a systematic review with meta-analysis. Materials and Methods: A Pubmed search of all studies comparing standardized incidence ratio (SIR) or odds ratio (OR) or relative risks (RR) of PC between IBD and non IBD groups, published until March 2020 was conducted. The study protocol was registered on PROSPERO. Twelve studies, mostly population studies, were included. The quality score of these studies, evaluated by the Newcastle-Ottawa Scale, was 7. The heterogeneity was high among the studies in which ulcerative colitis (UC) was considered separate from Crohn's disease (CD) and in the studies that considered UC and CD together ("IBD-studies"), while it was low in the studies which considered CD separate from UC. Results: The relative risk of developing PC was 1.71 (95% confidence interval [CI] 1.16-2.51, p = 0.007) in IBD, 1.10 (95%CI 0.98-1.25, p = 0.116) in CD, and 1.22 (95%CI 0.98-1.51, p = 0.07) in UC. Conclusions: Patients with IBD appear to have a slightly increased risk of PC compared to the general population.
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Affiliation(s)
- Edoardo Carli
- Unit of Gastroenterology, Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (S.R.); (G.M.S.); (D.G.R.)
| | | | - Rinaldo Pellicano
- Unit of Gastroenterology, Molinette Hospital, 10126 Turin, Italy; (R.P.); (M.A.)
| | - Sharmila Fagoonee
- Institute of Biostructure and Bioimaging, CNR c/o Molecular Biotechnology Centre, 10126 Turin, Italy;
| | - Stefano Rizza
- Unit of Gastroenterology, Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (S.R.); (G.M.S.); (D.G.R.)
| | - Marco Astegiano
- Unit of Gastroenterology, Molinette Hospital, 10126 Turin, Italy; (R.P.); (M.A.)
| | - Giorgio Maria Saracco
- Unit of Gastroenterology, Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (S.R.); (G.M.S.); (D.G.R.)
| | - Davide Giuseppe Ribaldone
- Unit of Gastroenterology, Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (S.R.); (G.M.S.); (D.G.R.)
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30
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Chen M, Yuan C, Xu T. An increase in prostate cancer diagnosis during inflammatory bowel disease: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 2020; 44:302-309. [PMID: 31447293 DOI: 10.1016/j.clinre.2019.07.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 07/13/2019] [Accepted: 07/16/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND In recent years, some studies showed that inflammatory bowel disease (IBD) might be associated with an increased risk of prostate cancer (PC), whereas some other studies indicated that IBD was not associated with the increased risk of PC. In the present study, we aimed to conduct a systematic review and meta-analysis to evaluate the association of IBD and PC risk. METHODS Web of Science and PubMed were systematically searched on for link of PC risk and IBD published from January 1976 to February 2019. The pooled multivariate odd ratio (OR) or relative risk (RR) and 95% confidence intervals (CI) were obtained by the use of STATA 12.0 software. RESULTS The meta-analysis indicated that IBD showed a 78% increase in PC risk (95% CI: 1.32-2.41). Sensitivity analyses showed no changes in the direction of effect after excluding any one study (supplementary figure 1). A significant heterogeneity was detected between different studies (Q test, P<0.001). Moreover, Begg's test, Egger's tests and funnel plots indicated no significant publication bias between included studies [Begg's test (P=0.371); Egger's test (p=0.100)]. CONCLUSION The present meta-analysis demonstrated that IBD was associated with an increased diagnosis of PC. In addition, large scale prospective studies are essential to determine whether IBD increase the PC risk.
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Affiliation(s)
- Mingshi Chen
- Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, N°321 Zhongshan Road, 210008 Nanjing, Jiangsu, China
| | - Caihong Yuan
- Department of Endocrinology, Kunshan Hospital on Integration of Chinese and Western Medicine, 215332 Jiangsu, China
| | - Tianshu Xu
- Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, N°321 Zhongshan Road, 210008 Nanjing, Jiangsu, China.
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31
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Golshani G, Zhang Y. Advances in immunotherapy for colorectal cancer: a review. Therap Adv Gastroenterol 2020; 13:1756284820917527. [PMID: 32536977 PMCID: PMC7268115 DOI: 10.1177/1756284820917527] [Citation(s) in RCA: 143] [Impact Index Per Article: 28.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Accepted: 03/17/2020] [Indexed: 02/04/2023] Open
Abstract
Immunotherapy is a new and exciting modality of cancer treatments. Its role in gastrointestinal malignancies has been promising, especially in advanced disease. Although various therapies are available for treatment of advanced colorectal cancer, survival rates for these patients remain very poor. The application of immunotherapy in colorectal cancer has shown remarkable results for a subset of patients with mismatch-repair-deficient mutations or microsatellite instability in their tumors. This literature review evaluates the current role of immunotherapy in advanced colorectal cancer, potential challenges clinicians face with immunotherapy-based regimens, and the possible future approach of combined modality immunotherapy.
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Affiliation(s)
- Gol Golshani
- Department of Medicine, Division of Hematology/Oncology, Stony Brook University Hospital, Stony Brook, NY, USA
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32
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Haddad A, Al-Sabbagh MQ, Al-Ani H, Siyam AM, Aborajooh E, Iwata T, Kimura S, Shariat SF, Abufaraj M. Inflammatory bowel disease and prostate cancer risk: A systematic review. Arab J Urol 2020; 18:207-212. [PMID: 33312730 PMCID: PMC7717159 DOI: 10.1080/2090598x.2020.1761674] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Objective: To evaluate the risk of prostate cancer (PCa) in patients with inflammatory bowel disease (IBD), focussing on ulcerative colitis (UC) and Crohn's disease (CD) separately. Methods: A systemic search was carried out using PubMed and Web of Science databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We retrieved a total of 349 articles. All the articles were in the English language and investigated the incidence of PCa in patients with IBD. Results: Nine studies met our inclusion criteria, with a total of 205 037 men. Two studies reported an increase in the risk of PCa in men with IBD in general. Five other studies reported an increased risk of PCa in men with UC or with CD specifically. On the other hand, two studies reported a decreased risk of PCa in patients with UC and patients with IBD treated with aminosalicylates. Conclusions: While men with UC appear to have higher risk of developing PCa, data on patients with CD are inconclusive. Therefore, patients with UC may benefit from earlier PCa screening. Our findings confirm a complex interplay between IBD and PCa, including factors such as genetic predisposition, systemic inflammation and treatment effects. The modulatory effect of treatment strategies for IBD on the development and progression of PCa might be of clinical significance. Abbreviations: CD: Crohn's disease; CRP: C- reactive protein; FOLH1: folate hydrolase 1; GIT: gastrointestinal tract; IBD: inflammatory bowel disease; IL-6: interleukin 6; NOS: Newcastle-Ottawa Scale; PCa: prostate cancer; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PSMA: prostate-specific membrane antigen; UC: ulcerative colitis.
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Affiliation(s)
- Anoud Haddad
- Division of Urology, Department of Special Surgery, Jordan University Hospital, the University of Jordan, Amman, Jordan
| | - Mohammed Qussay Al-Sabbagh
- Division of Urology, Department of Special Surgery, Jordan University Hospital, the University of Jordan, Amman, Jordan
| | - Hashim Al-Ani
- Division of Urology, Department of Special Surgery, Jordan University Hospital, the University of Jordan, Amman, Jordan
| | - Abdel Muez Siyam
- Division of Urology, Department of Special Surgery, Jordan University Hospital, the University of Jordan, Amman, Jordan
| | - Emad Aborajooh
- Department of Surgery, Faculty of Medicine, Mutah University, Kerak, Jordan
| | - Takehiro Iwata
- Department of Urology, Medical University of Vienna, Vienna, Austria.,Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Shoji Kimura
- Department of Urology, Medical University of Vienna, Vienna, Austria.,Department of Urology, Jikei University School of Medicine, Tokyo, Japan
| | - Shahrokh F Shariat
- Department of Urology, Medical University of Vienna, Vienna, Austria.,Department of Urology, Weill Cornell Medical College, New York, NY, USA.,Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.,Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria.,Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia
| | - Mohammad Abufaraj
- Division of Urology, Department of Special Surgery, Jordan University Hospital, the University of Jordan, Amman, Jordan.,Department of Urology, Medical University of Vienna, Vienna, Austria
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33
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Ge Y, Shi Q, Yao W, Cheng Y, Ma G. The association between inflammatory bowel disease and prostate cancer risk: a meta-analysis. Prostate Cancer Prostatic Dis 2019; 23:53-58. [PMID: 31591455 DOI: 10.1038/s41391-019-0177-7] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 08/07/2019] [Accepted: 08/26/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Patients with inflammatory bowel disease (IBD) are at increased risk of gastrointestinal and extraintestinal malignancies. However, the associations between IBD and prostate cancer (PCa) risk remain conflicting. METHODS We conducted a systematic literature search in PubMed, EMBASE, and Web of Science databases. According to the inclusion and exclusion criteria, a total of nine studies were included in the meta-analysis. The pooled standardized incidence ratios (SIRs) or relative risks (RRs) and corresponding 95% confidence intervals (CIs) were calculated to determine the relationship of IBD and PCa risk. RESULTS For cohort studies, the pooled SIR was 1.33 (95% CI = 1.03-1.71). The further subgroup analysis showed that the PCa risk was higher in patients with ulcerative colitis (UC) (pooled SIR = 1.58, 95% CI = 1.08-2.30), but not in patients with Crohn's disease (CD) (pooled SIR = 1.12, 95% CI = 0.97-1.31). Besides, for the three case-control studies, the results indicated that compared with normal group, the pooled RR of PCa was 1.81 for the patients with IBD (95% CI = 1.43-2.29). In addition, sensitivity analysis indicated that the results were robust and no significant publication bias were observed. CONCLUSIONS Our findings based on the large and multicenter samples strongly indicated that men with IBD especial UC have significantly elevated PCa risk. Future efforts are needed to define the mechanism underlying the link between IBD and PCa or clinically significant PCa risk.
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Affiliation(s)
- Yuqiu Ge
- Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu, China
| | - Qianqian Shi
- Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Wenxi Yao
- Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu, China
| | - Yang Cheng
- Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu, China.
| | - Gaoxiang Ma
- Clinical Metabolomics Center, China Pharmaceutical University, Nanjing, 211198, China. .,State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China.
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34
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Beckmann K, Russell B, Josephs D, Garmo H, Haggstrom C, Holmberg L, Stattin P, Van Hemelrijck M, Adolfsson J. Chronic inflammatory diseases, anti-inflammatory medications and risk of prostate cancer: a population-based case-control study. BMC Cancer 2019; 19:612. [PMID: 31226970 PMCID: PMC6588859 DOI: 10.1186/s12885-019-5846-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Accepted: 06/17/2019] [Indexed: 12/20/2022] Open
Abstract
Background Whether chronic inflammation increases prostate cancer risk remains unclear. This study investigated whether chronic inflammatory diseases (CID) or anti-inflammatory medication use (AIM) were associated with prostate cancer risk. Methods Fifty-five thousand nine hundred thirty-seven cases (all prostate cancer, 2007–2012) and 279,618 age-matched controls were selected from the Prostate Cancer Database Sweden. CIDs and AIMs was determined from national patient and drug registers. Associations were investigated using conditional logistic regression, including for disease/drug subtypes and exposure length/dose. Results Men with a history of any CID had slightly increased risk of any prostate cancer diagnosis (OR: 1.08; 95%CI: 1.04–1.12) but not ‘unfavourable’ (high-risk or advanced) prostate cancer. Generally, risk of prostate cancer was highest for shorter exposure times. However, a positive association was observed for asthma > 5 years before prostate cancer diagnosis (OR: 1.21; 95%CI: 1.05–1.40). Risk of prostate cancer was increased with prior use of any AIMs (OR: 1.26; 95%CI: 1.24–1.29). A positive trend with increasing cumulative dose was only observed for inhaled glucocorticoids (p < 0.011). Conclusion Detection bias most likely explains the elevated risk of prostate cancer with prior history of CIDs or use of AIMs, given the higher risk immediately after first CID event and lack of dose response. However, findings for length of time with asthma and dose of inhaled glucocorticoids suggest that asthma may increase risk of prostate cancer through other pathways. Electronic supplementary material The online version of this article (10.1186/s12885-019-5846-3) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Kerri Beckmann
- UniSA Cancer Research Institute, University of South Australia, Adelaide, Australia. .,School of Cancer and Pharmaceutical Studies, Translational Oncology & Urology Research (TOUR), King's College London, London, UK.
| | - Beth Russell
- School of Cancer and Pharmaceutical Studies, Translational Oncology & Urology Research (TOUR), King's College London, London, UK
| | - Debra Josephs
- School of Cancer and Pharmaceutical Studies, Translational Oncology & Urology Research (TOUR), King's College London, London, UK
| | - Hans Garmo
- School of Cancer and Pharmaceutical Studies, Translational Oncology & Urology Research (TOUR), King's College London, London, UK.,Regional Cancer Centre Uppsala, Uppsala University Hospital, Uppsala, Sweden
| | - Christel Haggstrom
- Department of Biobank Research, Umea University, Umea, Sweden.,Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden
| | - Lars Holmberg
- School of Cancer and Pharmaceutical Studies, Translational Oncology & Urology Research (TOUR), King's College London, London, UK.,Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden
| | - Pär Stattin
- Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden
| | - Mieke Van Hemelrijck
- School of Cancer and Pharmaceutical Studies, Translational Oncology & Urology Research (TOUR), King's College London, London, UK.,Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Jan Adolfsson
- CLINTEC-department, Karolinska Institutet, Stockholm, Sweden
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35
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Zhao H, Chen J, Chen J, Kong X, Zhu H, Zhang Y, Dong H, Wang J, Ren Q, Wang Q, Chen S, Deng Z, Chen Z, Cui Q, Zheng J, Lu J, Wang S, Tan J. miR-192/215-5p act as tumor suppressors and link Crohn's disease and colorectal cancer by targeting common metabolic pathways: An integrated informatics analysis and experimental study. J Cell Physiol 2019; 234:21060-21075. [PMID: 31020657 DOI: 10.1002/jcp.28709] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Revised: 04/02/2019] [Accepted: 04/11/2019] [Indexed: 12/25/2022]
Abstract
MicroRNAs have emerged as key regulators involved in a variety of biological processes. Previous studies have demonstrated that miR-192/215 participated in progression of Crohn's disease and colorectal cancer. However, their concrete relationships and regulation networks in diseases remain unclear. Here, we used bioinformatics methods to expound miR-192/215-5p macrocontrol regulatory networks shared by two diseases. For data mining and figure generation, several miRNA prediction tools, Human miRNA tissue atlas, FunRich, miRcancer, MalaCards, STRING, GEPIA, cBioPortal, GEO databases, Pathvisio, Graphpad Prism 6 software, etc . are extensively applied. miR-192/215-5p were specially distributed in colon tissues and enriched biological pathways were closely associated with human cancers. Emerging role of miR-192/215-5p and their common pathways in Crohn's disease and colorectal cancer was also analyzed. Based on results derived from multiple approaches, we identified the biological functions of miR-192/215-5p as a tumor suppressor and link Crohn's disease and colorectal cancer by targeting triglyceride synthesis and extracellular matrix remodeling pathways.
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Affiliation(s)
- Hu Zhao
- Department of Urology, Fujian Provincial Key Laboratory of Transplant Biology, 900 Hospital of the Joint Logistics Team, Xiamen University, Fuzhou, Fujian, China
| | - Junqiu Chen
- Department of Urology, Fujian Provincial Key Laboratory of Transplant Biology, 900 Hospital of the Joint Logistics Team, Xiamen University, Fuzhou, Fujian, China
| | - Jin Chen
- Department of Urology, Fujian Provincial Key Laboratory of Transplant Biology, 900 Hospital of the Joint Logistics Team, Xiamen University, Fuzhou, Fujian, China
| | - Xuhui Kong
- Department of Urology, Fujian Provincial Key Laboratory of Transplant Biology, 900 Hospital of the Joint Logistics Team, Xiamen University, Fuzhou, Fujian, China
| | - Hehuan Zhu
- Department of Urology, Fujian Provincial Key Laboratory of Transplant Biology, 900 Hospital of the Joint Logistics Team, Xiamen University, Fuzhou, Fujian, China
| | - Yongping Zhang
- Department of Neuro-oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas
| | - Huiyue Dong
- Department of Urology, Fujian Provincial Key Laboratory of Transplant Biology, 900 Hospital of the Joint Logistics Team, Xiamen University, Fuzhou, Fujian, China
| | - Jie Wang
- Department of Urology, Fujian Provincial Key Laboratory of Transplant Biology, 900 Hospital of the Joint Logistics Team, Xiamen University, Fuzhou, Fujian, China
| | - Qun Ren
- Department of Urology, Fujian Provincial Key Laboratory of Transplant Biology, 900 Hospital of the Joint Logistics Team, Xiamen University, Fuzhou, Fujian, China
| | - Qinghua Wang
- Department of Urology, Fujian Provincial Key Laboratory of Transplant Biology, 900 Hospital of the Joint Logistics Team, Xiamen University, Fuzhou, Fujian, China
| | - Shushang Chen
- Department of Urology, Fujian Provincial Key Laboratory of Transplant Biology, 900 Hospital of the Joint Logistics Team, Xiamen University, Fuzhou, Fujian, China
| | - Zhen Deng
- Department of Urology, Fujian Provincial Key Laboratory of Transplant Biology, 900 Hospital of the Joint Logistics Team, Xiamen University, Fuzhou, Fujian, China
| | - Zhan Chen
- Department of Urology, Fujian Provincial Key Laboratory of Transplant Biology, 900 Hospital of the Joint Logistics Team, Xiamen University, Fuzhou, Fujian, China
| | - Qiang Cui
- Department of Urology, Fujian Provincial Key Laboratory of Transplant Biology, 900 Hospital of the Joint Logistics Team, Xiamen University, Fuzhou, Fujian, China
| | - Junqiong Zheng
- Department of Oncology, Longyan First Hospital, Affiliated to Fujian Medical University, Longyan, Fujian, China
| | - Jun Lu
- Department of Urology, Fujian Provincial Key Laboratory of Transplant Biology, 900 Hospital of the Joint Logistics Team, Xiamen University, Fuzhou, Fujian, China
| | - Shuiliang Wang
- Department of Urology, Fujian Provincial Key Laboratory of Transplant Biology, 900 Hospital of the Joint Logistics Team, Xiamen University, Fuzhou, Fujian, China
| | - Jianming Tan
- Department of Urology, Fujian Provincial Key Laboratory of Transplant Biology, 900 Hospital of the Joint Logistics Team, Xiamen University, Fuzhou, Fujian, China
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Gomez-Rubio P, Piñero J, Molina-Montes E, Gutiérrez-Sacristán A, Marquez M, Rava M, Michalski CW, Farré A, Molero X, Löhr M, Perea J, Greenhalf W, O'Rorke M, Tardón A, Gress T, Barberá VM, Crnogorac-Jurcevic T, Muñoz-Bellvís L, Domínguez-Muñoz E, Balsells J, Costello E, Yu J, Iglesias M, Ilzarbe L, Kleeff J, Kong B, Mora J, Murray L, O'Driscoll D, Poves I, Lawlor RT, Ye W, Hidalgo M, Scarpa A, Sharp L, Carrato A, Real FX, Furlong LI, Malats N. Pancreatic cancer and autoimmune diseases: An association sustained by computational and epidemiological case-control approaches. Int J Cancer 2019; 144:1540-1549. [PMID: 30229903 DOI: 10.1002/ijc.31866] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Revised: 07/18/2018] [Accepted: 07/27/2018] [Indexed: 12/17/2022]
Abstract
Deciphering the underlying genetic basis behind pancreatic cancer (PC) and its associated multimorbidities will enhance our knowledge toward PC control. The study investigated the common genetic background of PC and different morbidities through a computational approach and further evaluated the less explored association between PC and autoimmune diseases (AIDs) through an epidemiological analysis. Gene-disease associations (GDAs) of 26 morbidities of interest and PC were obtained using the DisGeNET public discovery platform. The association between AIDs and PC pointed by the computational analysis was confirmed through multivariable logistic regression models in the PanGen European case-control study population of 1,705 PC cases and 1,084 controls. Fifteen morbidities shared at least one gene with PC in the DisGeNET database. Based on common genes, several AIDs were genetically associated with PC pointing to a potential link between them. An epidemiologic analysis confirmed that having any of the nine AIDs studied was significantly associated with a reduced risk of PC (Odds Ratio (OR) = 0.74, 95% confidence interval (CI) 0.58-0.93) which decreased in subjects having ≥2 AIDs (OR = 0.39, 95%CI 0.21-0.73). In independent analyses, polymyalgia rheumatica, and rheumatoid arthritis were significantly associated with low PC risk (OR = 0.40, 95%CI 0.19-0.89, and OR = 0.73, 95%CI 0.53-1.00, respectively). Several inflammatory-related morbidities shared a common genetic component with PC based on public databases. These molecular links could shed light into the molecular mechanisms underlying PC development and simultaneously generate novel hypotheses. In our study, we report sound findings pointing to an association between AIDs and a reduced risk of PC.
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Affiliation(s)
- Paulina Gomez-Rubio
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center CNIO, Madrid, Spain
- Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
| | - Janet Piñero
- Research Program on Biomedical Informatics (GRIB), Hospital del Mar Research Institute (IMIM), Universidad Pompeu Fabra (UPF), Barcelona, Spain
| | - Esther Molina-Montes
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center CNIO, Madrid, Spain
- Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
| | - Alba Gutiérrez-Sacristán
- Research Program on Biomedical Informatics (GRIB), Hospital del Mar Research Institute (IMIM), Universidad Pompeu Fabra (UPF), Barcelona, Spain
| | - Mirari Marquez
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center CNIO, Madrid, Spain
- Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
| | - Marta Rava
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center CNIO, Madrid, Spain
- Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
| | - Christoph W Michalski
- Department of Surgery, Technical University of Munich, Munich, Germany
- Department of Surgery, University of Heidelberg, Heidelberg, Germany
| | - Antoni Farré
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Xavier Molero
- Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
- Hospital Universitaru Vall d'Hebron, Exocrine Pancreas Research Unit and Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
- Universitat Auntònoma de Barcelona, Campus de la UAB, Barcelona, Spain
| | - Matthias Löhr
- Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and University Hospital, Stockholm, Sweden
| | - José Perea
- Department of Surgery, University Hospital 12 de Octubre, Madrid, Spain
| | - William Greenhalf
- Department of Molecular and Clinical Cancer Medicine, The Royal Liverpool University Hospital, Liverpool, United Kingdom
| | - Michael O'Rorke
- Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom
| | - Adonina Tardón
- Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
- Department of Medicine, Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain
| | - Thomas Gress
- Department of Gastroenterology, University Hospital of Giessen and Marburg, Marburg, Germany
| | - Victor M Barberá
- Laboratorio de Genética Molecular, Hospital General Universitario de Elche, Elche, Spain
| | - Tatjana Crnogorac-Jurcevic
- Centre for Molecular Oncology, John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom
| | - Luís Muñoz-Bellvís
- General and Digestive Surgery Department, Hospital Universitario de Salamanca, Salamanca, Spain
| | - Enrique Domínguez-Muñoz
- Department of Gastroenterology, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
| | - Joaquim Balsells
- Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
- Hospital Universitaru Vall d'Hebron, Exocrine Pancreas Research Unit and Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
- Universitat Auntònoma de Barcelona, Campus de la UAB, Barcelona, Spain
| | - Eithne Costello
- Department of Molecular and Clinical Cancer Medicine, The Royal Liverpool University Hospital, Liverpool, United Kingdom
| | - Jingru Yu
- Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and University Hospital, Stockholm, Sweden
| | - Mar Iglesias
- Department of Gastroenterology, Hospital del Mar/Parc de Salut Mar, Barcelona, Spain
| | - Lucas Ilzarbe
- Department of Gastroenterology, Hospital del Mar/Parc de Salut Mar, Barcelona, Spain
| | - Jörg Kleeff
- Department of Surgery, Technical University of Munich, Munich, Germany
- Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, Halle, (Saale), Germany
| | - Bo Kong
- Department of Surgery, Technical University of Munich, Munich, Germany
| | - Josefina Mora
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Liam Murray
- Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom
| | - Damian O'Driscoll
- Cancer Data Registrars, National Cancer Registry Ireland, Cork, Ireland
| | - Ignasi Poves
- Department of Gastroenterology, Hospital del Mar/Parc de Salut Mar, Barcelona, Spain
| | - Rita T Lawlor
- ARC-Net Centre for Applied Research on Cancer, Department of Pathology and Diagnostics, University Hospital Trust of Verona, Verona, Italy
| | - Weimin Ye
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet and University Hospital, Sweden
| | - Manuel Hidalgo
- Hospital Madrid-Norte-Sanchinarro and Spanish National Cancer Research Centre (CNIO), Madrid, Spain
- Rosenberg Clinical Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
| | - Aldo Scarpa
- ARC-Net Centre for Applied Research on Cancer, Department of Pathology and Diagnostics, University Hospital Trust of Verona, Verona, Italy
| | - Linda Sharp
- Cancer Data Registrars, National Cancer Registry Ireland, Cork, Ireland
- Institute of Health and Society, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Alfredo Carrato
- Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
- Department of Oncology, Hospital Ramón y Cajal, Madrid, Spain
| | - Francisco X Real
- Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
- Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
- Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
| | - Laura I Furlong
- Research Program on Biomedical Informatics (GRIB), Hospital del Mar Research Institute (IMIM), Universidad Pompeu Fabra (UPF), Barcelona, Spain
| | - Núria Malats
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center CNIO, Madrid, Spain
- Centro de Investigación Biomédica en Red en Oncología (CIBERONC), Enfermedades Hepáticas y Digestivas (CIBERHD), and Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
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Wong JJ, Sceats L, Dehghan M, Wren AA, Sellers ZM, Limketkai BN, Bensen R, Kin C, Park KT. Depression and Health Care Use in Patients With Inflammatory Bowel Disease. J Crohns Colitis 2019; 13:19-26. [PMID: 30256923 DOI: 10.1093/ecco-jcc/jjy145] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Depression frequently co-occurs in patients with inflammatory bowel disease [IBD] and is a driver in health care costs and use. AIM This study examined the associations between depression and total health care costs, emergency department [ED] visits, computed tomography [CT] during ED/inpatient visits, and IBD-related surgery among IBD patients. METHODS Our sample included 331772 IBD patients from a national administrative claims database [Truven Health MarketScan® Database]. Gamma and Poisson regression analyses assessed differences related to depression, controlling for key variables. RESULTS Approximately 16% of the IBD cohort was classified as having depression. Depression was associated with a $17,706 (95% confidence interval [CI] [$16,892, 18,521]) increase in mean annual IBD-related health care costs and an increased incidence of ED visits (adjusted incidence rate ratio [aIRR] of 1.5; 95% CI [1.5, 1.6]). Among patients who had one or more ED/inpatient visits, depression was associated with an increased probability of receiving repeated CT [one to four scans, adjusted odds ratio [aOR] of 1.6; 95% CI [1.5, 1.7]; five or more scans, aOR of 4.6; 95% CI [2.9, 7.3]) and increased odds of undergoing an IBD-related surgery (aOR of 1.2; 95% CI [1.1, 1.2]). Secondary analysis with a paediatric subsample revealed that approximately 12% of this cohort was classified as having depression, and depression was associated with increased costs and incidence rates of ED visits and CT, but not of IBD-related surgery. CONCLUSIONS Quantifiable differences in health care costs and patterns of use exist among patients with IBD and depression. Integration of mental health services within IBD care may improve overall health outcomes and costs of care.
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Affiliation(s)
- Jessie J Wong
- Pediatric Endocrinology, Stanford University School of Medicine, Stanford, CA, USA
| | - Lindsay Sceats
- Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Melody Dehghan
- Stanford Children's Inflammatory Bowel Disease Center, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Anava A Wren
- Stanford Children's Inflammatory Bowel Disease Center, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Zachary M Sellers
- Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Berkeley N Limketkai
- Division of Gastroenterology & Hepatology, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Rachel Bensen
- Stanford Children's Inflammatory Bowel Disease Center, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Cindy Kin
- Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - K T Park
- Stanford Children's Inflammatory Bowel Disease Center, Stanford University School of Medicine, Palo Alto, CA, USA
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38
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Goodman B, Gardner H. The microbiome and cancer. J Pathol 2018; 244:667-676. [PMID: 29377130 DOI: 10.1002/path.5047] [Citation(s) in RCA: 118] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Revised: 01/11/2018] [Accepted: 01/17/2018] [Indexed: 12/12/2022]
Abstract
Humans coexist with a vast bacterial, fungal and viral microbiome with which we have coevolved for millions of years. Several long recognized epidemiological associations between particular bacteria and cancer are now understood at the molecular level. At the same time, the arrival of next-generation sequencing technology has permitted a thorough exploration of microbiomes such as that of the human gut, enabling observation of taxonomic and metabolomic relationships between the microbiome and cancer. These studies have revealed causal mechanisms for both microbes within tumours and microbes in other host niches separated from tumours, mediated through direct and immunological mechanisms. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Hazenberg HMJL, de Boer NKH, Mulder CJJ, Mom SH, van Bodegraven AA, Tack Md PhD GJ. Neoplasia and Precursor Lesions of the Female Genital Tract in IBD: Epidemiology, Role of Immunosuppressants, and Clinical Implications. Inflamm Bowel Dis 2018; 24:510-531. [PMID: 29462389 DOI: 10.1093/ibd/izx062] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2017] [Indexed: 12/13/2022]
Abstract
In this review the risk of breast, ovarian, and endometrial cancer and cervical and vulvovaginal (pre)malignant abnormalities in patients with inflammatory bowel disease (IBD) with or without immune suppressive treatment will be discussed. So far, this has not been studied thoroughly and large studies taking into account diverse potential confounding factors are lacking. IBD per se has not been associated with development of cervical cancer, yet patients with Crohn's disease who smoke, have a younger age at diagnosis or who use(d) thiopurines might be more at risk. Other immunosuppressive medication seems not to increase this risk, however, as evidence at this point is incomplete, physician awareness and prevention by lifestyle counseling, HPV vaccination and (intensified) screening are warranted. The risk for breast, endometrial, ovarian, and vulvovaginal cancer in IBD patients appears to be comparable to the background population, although for breast cancer this may even be decreasedin Crohn's disease specifically. Immunosuppressive medication in general does not seem to alter this risk. Earlier and more frequent screening for breast cancer than currently conducted in general nationwide screening programs is not recommended at this moment. Current literature suggests a much lower overall malignancy recurrence rate in IBD patients than has been observed previously. More importantly, immune suppressive medication does not appear to increase the recurrence risk. Robust epidemiologic data on female genital tract cancer are needed.
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Affiliation(s)
- Hanna M J L Hazenberg
- Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam
| | - Nanne K H de Boer
- Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam
| | - Chris J J Mulder
- Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam
| | - Stijn H Mom
- Department of Obstetrics and Gynaecology, VU University Medical Center, Amsterdam
| | - Ad A van Bodegraven
- Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam.,Department of Gastroenterology, Geriatrics, Internal and Intensive Care Medicine (Co-MIK), Zuyderland Medical Center, Heerlen-Sittard-Geleen
| | - Greetje J Tack Md PhD
- Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam.,Department of Gastroenterology and Hepatology, Medical Center Leeuwarden, Leeuwarden
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Schairer C, Pfeiffer RM, Gadalla SM. Autoimmune diseases and breast cancer risk by tumor hormone-receptor status among elderly women. Int J Cancer 2017; 142:1202-1208. [PMID: 29144542 DOI: 10.1002/ijc.31148] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2017] [Revised: 10/13/2017] [Accepted: 10/17/2017] [Indexed: 12/19/2022]
Abstract
The female preponderance of many autoimmune diseases suggests a possible hormonal etiology. Little research exists on systemic and organ-specific autoimmune diseases and risk of breast cancer by tumor estrogen receptor (ER)- and progesterone receptor (PR)- status. Here, we evaluate associations between selected systemic and organ-specific autoimmune diseases and breast cancer risk overall and by tumor ER- and PR-status. We used linked Surveillance, Epidemiology and End Results (SEER)-Medicare data, with first female breast cancer cases ages ≥66 years identified by SEER registries (years 1992-2011; N = 209,929). We selected female controls (N = 200,000) from a stratified 5% random sample of Medicare recipients who were alive and breast cancer-free. We assessed exposures until 12 months before breast cancer diagnosis/selection using Medicare claims data. We estimated odds ratios (OR) and 99.9% confidence intervals (CI) using unconditional and multinomial logistic regression. We found reduced breast cancer risk among those with rheumatoid arthritis (OR = 0.84; 99.9% CI 0.79-0.89), systemic lupus erythematosus (OR = 0.82; 99.9% CI 0.70-0.97) and pernicious anemia (OR = 0.90; 99.9% CI 0.83-0.97) and increased risk among those with psoriasis (OR = 1.16; 99.9% CI 1.06-1.27). Statistically significant alterations in risk for rheumatoid arthritis were limited to ER-positive (+) breast cancer, whereas those for the other three conditions were further limited to ER+/PR+ breast cancer. However, only differences for rheumatoid arthritis by ER-status were statistically significant (p-heterogeneity = 0.0001). The reasons for these associations need to be investigated in future studies accounting for host characteristics and autoimmune disease treatment.
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Affiliation(s)
- Catherine Schairer
- National Cancer Institute, Division of Cancer Epidemiology and Genetics, National Institutes of Health, Bethesda, MD
| | - Ruth M Pfeiffer
- National Cancer Institute, Division of Cancer Epidemiology and Genetics, National Institutes of Health, Bethesda, MD
| | - Shahinaz M Gadalla
- National Cancer Institute, Division of Cancer Epidemiology and Genetics, National Institutes of Health, Bethesda, MD
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Santos SCDD, Barbosa LER. Crohn's disease: risk factor for colorectal cancer. JOURNAL OF COLOPROCTOLOGY 2017. [DOI: 10.1016/j.jcol.2016.06.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/11/2023]
Abstract
Abstract
Background Crohn's disease is an inflammatory disease that can reach any part of the gastrointestinal tract. This disease has been associated with an increased neoplastic risk, including colorectal carcinoma.
Objective The objective of this work is to describe the mechanisms present in two diseases, and that are responsible for the increased risk in Crohn's disease.
Methods A bibliographic research was conducted in PubMed database. In addition to the articles obtained with an inserted query in Pubmed, other references relevant to the topic in question were included.
Results Colorectal cancer risk varies according to the presence of certain factors, and an example of this is Crohn's disease. Chronic inflammation seems to be an important contribution to carcinogenesis, since it creates a microenvironment suitable for the onset and progression of the disease. There are molecular changes that are common to two conditions, thus justifying the fact of Crohn's disease being a risk factor for colorectal carcinoma. The disease control with an appropriate therapy and with surveillance are two ways to control this risk.
Conclusions A proinflammatory state is the cornerstone in the association between Crohn's disease and colorectal carcinoma. The implementation of surveillance strategies allowed a decrease in morbidity and mortality associated with this cancer.
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Affiliation(s)
| | - Laura Elisabete Ribeiro Barbosa
- Universidade do Porto, Faculdade de Medicina, Porto, Portugal
- Hospital de São João, Serviço de Cirurgia Geral, Porto, Portugal
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Ilic M, Ilic I. Epidemiology of pancreatic cancer. World J Gastroenterol 2016; 22:9694-9705. [PMID: 27956793 PMCID: PMC5124974 DOI: 10.3748/wjg.v22.i44.9694] [Citation(s) in RCA: 939] [Impact Index Per Article: 104.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2016] [Revised: 08/30/2016] [Accepted: 09/28/2016] [Indexed: 02/06/2023] Open
Abstract
Cancer of the pancreas remains one of the deadliest cancer types. Based on the GLOBOCAN 2012 estimates, pancreatic cancer causes more than 331000 deaths per year, ranking as the seventh leading cause of cancer death in both sexes together. Globally, about 338000 people had pancreatic cancer in 2012, making it the 11th most common cancer. The highest incidence and mortality rates of pancreatic cancer are found in developed countries. Trends for pancreatic cancer incidence and mortality varied considerably in the world. A known cause of pancreatic cancer is tobacco smoking. This risk factor is likely to explain some of the international variations and gender differences. The overall five-year survival rate is about 6% (ranges from 2% to 9%), but this vary very small between developed and developing countries. To date, the causes of pancreatic cancer are still insufficiently known, although certain risk factors have been identified, such as smoking, obesity, genetics, diabetes, diet, inactivity. There are no current screening recommendations for pancreatic cancer, so primary prevention is of utmost importance. A better understanding of the etiology and identifying the risk factors is essential for the primary prevention of this disease.
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Wilson JC, Furlano RI, Jick SS, Meier CR. A population-based study examining the risk of malignancy in patients diagnosed with inflammatory bowel disease. J Gastroenterol 2016; 51:1050-1062. [PMID: 27056729 DOI: 10.1007/s00535-016-1199-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Accepted: 03/11/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUND Recent studies suggest an increased risk of malignancy in patients with inflammatory bowel disease (IBD), although the findings were inconsistent. We used data from the clinical practice research datalink (CPRD) to further examine this association. METHODS Patients with a first-time diagnosis of IBD were randomly matched to an equally sized IBD-free comparison group. Multivariable adjusted hazard ratios (AHRs) for cancer risk were estimated using Cox's proportional hazard regression. A nested case-control analysis comprising IBD patients only was then conducted using conditional logistic regression to estimate the risk of cancer development according to IBD severity, disease duration and IBD therapy. RESULTS We identified 1077 cancers among 39,294 IBD or IBD-free patients followed between 1995 and 2012. There was no association between IBD and overall risk of cancer [AHR 1.11, 95 % confidence interval (CI) 0.98-1.25], but a borderline increase in the risk of lymphoproliferative malignancies was observed in patients with IBD (AHR 1.49, 95 % CI 1.00-2.23). Aminosalicylate use was significantly associated with reduced risk of all cancers [adjusted odds ratio (AOR), 0.72, 95 % CI 0.54-0.96], of intestinal cancer (AOR 0.33, 95 % 0.12-0.89) and of prostate cancer (AOR 0.32, 95 % 0.13-0.80). CONCLUSIONS There was no increased risk of cancer overall in individuals with IBD compared to IBD-free individuals. Consistent with previous findings, a reduction in cancer risk was observed in IBD patients using aminosalicylates, with a substantial reduction in prostate cancer risk. Further large-scale studies examining the relationship between IBD therapy and cancer risk appear to be warranted.
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Affiliation(s)
- J Claire Wilson
- Basel Pharmacoepidemiology Unit (BPU), Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
| | | | - Susan S Jick
- Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Lexington, MA, USA
| | - Christoph R Meier
- Basel Pharmacoepidemiology Unit (BPU), Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
- University Hospital Basel, Basel, Switzerland.
- Hospital Pharmacy, Spitalstrasse 26, 4031, Basel, Switzerland.
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Griffey RT, Fowler KJ, Theilen A, Gutierrez A. Considerations in Imaging Among Emergency Department Patients With Inflammatory Bowel Disease. Ann Emerg Med 2016; 69:587-599. [PMID: 27317304 DOI: 10.1016/j.annemergmed.2016.04.010] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2015] [Revised: 03/15/2016] [Accepted: 04/05/2016] [Indexed: 12/16/2022]
Abstract
Patients with inflammatory bowel disease who experience abdominal pain and gastrointestinal symptoms often seek care in the emergency department (ED). These patients commonly undergo abdominopelvic computed tomography (CT) as part of their evaluation, and the rate of imaging appears to be increasing without a corresponding increase in identification of clinically actionable findings or effect on disposition. Studies demonstrate that the yield of CT tends to be fairly high. Yet, because inflammatory bowel disease is often diagnosed at an early age, these patients are repeatedly imaged during their lifetime, a subset of whom accumulate high levels of ionizing radiation exposure, increasing their risk of cancer. This compounds an already increased risk of cancer in these patients because of inflammatory bowel disease alone. Lack of intimate knowledge of a patient's disease phenotype and disease progression contributes to uncertainty in distinguishing between an inflammatory exacerbation; a complication such as obstruction, abscess, perforation, fistula, or stricture; and a noninflammatory-bowel-disease-related condition. This uncertainty can lead to overuse of imaging with CT. Limited availability of and lack of awareness of alternate imaging modalities and strategies may prevent providers from pursuing strategies that avoid ionizing radiation. In this article, we review options for imaging inflammatory bowel disease patients in the ED and attempts undertaken to risk stratify these patients, and we discuss ways in which details of a patient's disease might guide imaging decisionmaking.
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Affiliation(s)
- Richard T Griffey
- Division of Emergency Medicine, Washington University School of Medicine, St. Louis, MO.
| | - Kathryn J Fowler
- Department of Radiology, Washington University School of Medicine, St. Louis, MO
| | - Andrew Theilen
- Division of Emergency Medicine, Washington University School of Medicine, St. Louis, MO
| | - Alexandra Gutierrez
- Division of Gastroenterology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO
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Crohn's disease Activity: Abdominal Computed Tomography Histopathology Correlation. Eur J Radiol Open 2016; 3:74-78. [PMID: 27957517 PMCID: PMC5144110 DOI: 10.1016/j.ejro.2016.03.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2016] [Accepted: 03/03/2016] [Indexed: 01/18/2023] Open
Abstract
Purpose Crohn’s disease is a type of inflammatory bowel disease affecting estimated 4 million people worldwide. Therapy stratification of Crohn’s disease (CD) is mainly based on the inflammatory activity being assessed by endoscopic biopsy and clinical criteria. Cross-sectional imaging allows for the assessment of structural characteristics of the entire gastrointestinal tract including small bowel loops and may provide potential non-invasive image-based biomarkers for the inflammatory activity of CD. The aim of this study was to explore the predictive value of Computed Tomography-based morphologic patterns for inflammatory activity in CD. Material and methods 42 patients diagnosed with CD were included in a retrospective study (13 male, 29 female, median age 32 years). Abdominal CT imaging was carried out on symptomatic patients at a single institution 0–10 days prior to endoscopic biopsy or surgery using a protocol optimized for the characterization of structural bowel alterations. Image data were initially reviewed independently by three radiologists and discrepancies were settled in consensus with a focus on mesenteric fat stranding and combing, mesenteric adenopathy, mesenteric abscess, intraperitoneal free fluid, fistula, skip lesions, highest wall thickness and the localization of the affected bowel. The extent of inflammatory activity in the bowel wall was determined subsequently by histological analysis. Results All intestinal and extraintestinal CT findings except the mesenteric comb sign showed a tendency towards higher extent or prevalence in patients with high histological inflammatory activity score, especially median bowel wall thickness (6.0 mm vs. 3.5 mm), mesenteric abscesses (32% vs. 0%) and mesenteric adenopathy (94% vs. 45%). Spearman rank order correlation coefficient indicated a significant correlation of bowel wall thickness (r = 0.40, p < 0.05), mesenteric adenopathy (r = 0.54, p < 0.05), mesenteric abscess (r = 0.33, p < 0.05) and mesenteric fat stranding (r = 0.33, p < 0.05) with the histological inflammatory activity score. Conclusion CT-based biomarkers including wall thickness, mesenteric fat stranding, mesenteric lymphadenopathy and mesenteric abscess positively correlated with the histological inflammatory activity score and therefore provided additional information for therapy stratification in symptomatic patients with CD, particularly as most of these biomarkers are hidden from endoscopy.
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Ou B, Zhao J, Guan S, Lu A. Survival of Colorectal Cancer in Patients With or Without Inflammatory Bowel Disease: A Meta-Analysis. Dig Dis Sci 2016; 61:881-9. [PMID: 26518415 DOI: 10.1007/s10620-015-3940-1] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2015] [Accepted: 10/22/2015] [Indexed: 12/14/2022]
Abstract
BACKGROUND Patients with inflammatory bowel disease (IBD) are at increased risk of colorectal cancer (CRC), but little is known about the influence of IBD on CRC prognosis. AIMS The aim of this study was to perform a meta-analysis to compare survival in CRC patients with IBD (IBD-CRC) and without IBD. METHODS An electronic search was conducted via PubMed, Embase, and the Cochrane Library to identify eligible trials until July 2015. We pooled the hazard ratios (HRs) and their 95% confidence intervals (CIs) to quantitatively assess the survival of CRC in patients with or without IBD. In addition, clinicopathological parameters of IBD-CRC versus non-IBD CRC were evaluated. RESULTS Twelve studies containing a total of 3472 IBD-CRC patients were eligible according to our selection criteria. Our analysis indicated that CRC patients with IBD had shorter overall survival than those without IBD (HR 1.24, 95% CI 1.19-1.29). IBD-CRC showed a propensity to develop in proximal colon [odds ratio (OR) 2.52, 95% CI 1.35-4.72] and correlated with worse differentiation of tumor (OR 1.59, 95% CI 1.26-1.99) compared to non-IBD CRC. Meta-regression analysis showed that sample size (P = 0.002) could explain 99.01% inter-study heterogeneity. CONCLUSION This meta-analysis found poorer overall survival in CRC patients with IBD than CRC patients without IBD, and further prospective research to confirm these findings is warranted.
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Affiliation(s)
- Baochi Ou
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Jingkun Zhao
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Shaopei Guan
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Aiguo Lu
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
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Gloux K, Anba-Mondoloni J. Unique β-Glucuronidase Locus in Gut Microbiomes of Crohn's Disease Patients and Unaffected First-Degree Relatives. PLoS One 2016; 11:e0148291. [PMID: 26824357 PMCID: PMC4732671 DOI: 10.1371/journal.pone.0148291] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2015] [Accepted: 01/15/2016] [Indexed: 12/24/2022] Open
Abstract
Crohn's disease, an incurable chronic inflammatory bowel disease, has been attributed to both genetic predisposition and environmental factors. A dysbiosis of the gut microbiota, observed in numerous patients but also in at least one hundred unaffected first-degree relatives, was proposed to have a causal role. Gut microbiota β-D-glucuronidases (EC 3.2.1.33) hydrolyse β-D-glucuronate from glucuronidated compounds. They include a GUS group, that is homologous to the Escherichia coli GusA, and a BG group, that is homologous to metagenomically identified H11G11 BG and has unidentified natural substrates. H11G11 BG is part of the functional core of the human gut microbiota whereas GusA, known to regenerate various toxic products, is variably found in human subjects. We investigated potential risk markers for Crohn's disease using DNA-sequence-based exploration of the β-D-glucuronidase loci (GUS or Firmicute H11G11-BG and the respective co-encoded glucuronide transporters). Crohn's disease-related microbiomes revealed a higher frequency of a C7D2 glucuronide transporter (12/13) compared to unrelated healthy subjects (8/32). This transporter was in synteny with the potential harmful GUS β-D-glucuronidase as only observed in a Eubacterium eligens plasmid. A conserved NH2-terminal sequence in the transporter (FGDFGND motif) was found in 83% of the disease-related subjects and only in 12% of controls. We propose a microbiota-pathology hypothesis in which the presence of this unique β-glucuronidase locus may contribute to an increase risk for Crohn's disease.
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Affiliation(s)
- Karine Gloux
- Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France
- * E-mail:
| | - Jamila Anba-Mondoloni
- Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France
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Recurrent Hepatocellular Carcinoma in Patient with Crohn's Disease: Incidental or Expected Outcome of Azathioprine? Case Rep Gastrointest Med 2016; 2015:939136. [PMID: 26788381 PMCID: PMC4691603 DOI: 10.1155/2015/939136] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2015] [Revised: 11/20/2015] [Accepted: 11/25/2015] [Indexed: 12/02/2022] Open
Abstract
Hepatocellular carcinoma (HCC) usually occurs in patients with underlying risk factors such as liver cirrhosis and chronic hepatitis B. Although patients with Crohn's disease (CD) are at an increased risk to develop malignancies such as colon cancer, the incidence of HCC in this population is extremely rare. We report a case of 62-year-old male with long history of CD treated with azathioprine (AZA) and aminosalicylic acid (ASA) who was incidentally diagnosed with HCC, for which left hepatectomy was done. Four years later during routine follow-up, patient had another hepatic lesion and underwent resection of the mass. The mechanism of occurrence of HCC in patient with CD is still controversial and may include immune mediated changes and medication related complications. AZA was reported in all case reports of CD that developed HCC. Through this report we hope to explore the complex pathophysiological mechanisms contributing to the development of HCC in the Crohn's disease patient population.
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Lee J, Clarke K. Anti-TNF agents in patients with inflammatory bowel disease and malignant melanoma--challenges in management. Int J Colorectal Dis 2015; 30:1595-602. [PMID: 26349591 DOI: 10.1007/s00384-015-2344-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/27/2015] [Indexed: 02/04/2023]
Abstract
PURPOSE The inflammatory bowel diseases (IBD) are chronic immune-mediated inflammatory diseases of the gut that occur in genetically predisposed individuals exposed to environmental triggers. Several immunosuppressive agents have been successfully used for induction and maintenance treatment in inflammatory bowel disease. These include steroids, thiopurines, methotrexate, anti-tumor necrosis factor (anti-TNF) alpha agents, anti-alpha 4 integrins, and anti-IL-12/23 agent to name a few. There are also limited data on novel approaches including thalidomide and stem cell transplant. In spite of the significant successes associated with these agents, numerous malignancies have been associated with their use. Lymphomas including hepatosplenic T cell lymphomas, non-melanoma skin cancers and, more recently, melanoma have been described, specifically with anti-TNF. METHODS We reviewed the available published literature on melanoma in IBD, melanoma associated with anti-TNF, and the data on other treatment options in patients with IBD. In addition, we also reviewed the limited data on the gut specific integrin-vedolizumab. This may provide an additional option in the management of the subset of patients with IBD and melanoma. RESULTS Options for treatment of IBD should be based on the stage of melanoma, control of IBD, and patient preferences. It should involve shared decision-making and close interdisciplinary follow-up between the IBD physician and the dermatologist, preferably with expertise in the management of melanoma. CONCLUSIONS Treatment choices in patients with IBD and melanoma are challenging. There is very limited data providing guidance in this subset of patients. As such, treatment and follow-up should be individualized, extensively discussed with patients and their families as appropriate, and done in conjunction with a close follow-up by gastroenterologist and dermatologist.
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Affiliation(s)
- Jungmin Lee
- Department of Medicine, Allegheny Health Network, Pittsburgh, PA, 15212, USA
| | - Kofi Clarke
- Department of Medicine, Allegheny Health Network, Pittsburgh, PA, 15212, USA. .,Division of Gastroenterology, Allegheny Health Network, Pittsburgh, PA, 15212, USA.
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Lawlor G, Katz S. Management of IBD in the Elderly Patient With Cancer. CURRENT TREATMENT OPTIONS IN GASTROENTEROLOGY 2015; 13:301-307. [PMID: 26135089 DOI: 10.1007/s11938-015-0061-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
The management of inflammatory bowel disease (IBD) in patients with known or recently treated cancer has become a common dilemma in our ageing population. Older patients are commonly excluded from prospective trials, and co-morbid status and polypharmacy may muddy our understanding of the impact of therapies on these patients. Immunosuppression (anti-TNF therapy, antimetabolite therapy) carries a relative contra-indication in the setting of known cancer as it is expected to increase cancer risk and increase propagation of in situ cancer. Recent studies have sought to investigate this risk by looking from two sides-the impact of cancer therapies on IBD outcomes and the risk of cancer occurrence/recurrence in patients on IBD therapies. In this chapter, we review this data and determine the safety of commonly used IBD therapies in this potentially vulnerable elderly population.
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Affiliation(s)
- Garrett Lawlor
- Inflammatory Bowel Disease Program, Columbia University Medical Center, 161 Fort Washington Ave, Suite 862, New York, NY, 10032, USA,
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