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Yuan T, Xing J, Liu P. Identification of Crohn's Disease-Related Biomarkers and Pan-Cancer Analysis Based on Machine Learning. Mediators Inflamm 2025; 2025:6631637. [PMID: 40224483 PMCID: PMC11991868 DOI: 10.1155/mi/6631637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Accepted: 03/14/2025] [Indexed: 04/15/2025] Open
Abstract
Background: In recent years, the incidence of Crohn's disease (CD) has shown a significant global increase, with numerous studies demonstrating its correlation with various cancers. This study aims to identify novel biomarkers for diagnosing CD and explore their potential applications in pan-cancer analysis. Methods: Gene expression profiles were retrieved from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified using the "limma" R package. Key biomarkers were selected through an integrative machine learning pipeline combining LASSO regression, neural network modeling, and Support Vector Machine-Recursive Feature Elimination (SVM-RFE). Six hub genes were identified and further validated using the independent dataset GSE169568. To assess the broader relevance of these biomarkers, a standardized pan-cancer dataset from the UCSC database was analyzed to evaluate their associations with 33 cancer types. Results: Among the identified biomarkers, S100 calcium binding protein P (S100P) and S100 calcium binding protein A8 (S100A8) emerged as key candidates for CD diagnosis, with strong validation in the independent dataset. Notably, S100P displayed significant associations with immune cell infiltration and patient survival outcomes in both liver and lung cancers. These findings suggest that chronic inflammation and immune imbalances in CD may not only contribute to disease progression but also elevate cancer risk. As an inflammation-associated biomarker, S100P holds particular promise for both CD diagnosis and potential cancer risk stratification, especially in liver and lung cancers. Conclusion: Our study highlights S100P and S100A8 as potential diagnostic biomarkers for CD. Moreover, the pan-cancer analysis underscores the broader clinical relevance of S100P, offering new insights into its role in immune modulation and cancer prognosis. These findings provide a valuable foundation for future research into the shared molecular pathways linking chronic inflammatory diseases and cancer development.
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Affiliation(s)
- Tangyu Yuan
- School of Life Science and Technology, Shandong Second Medical University, Weifang, Shandong, China
| | - Jiayin Xing
- School of Life Science and Technology, Shandong Second Medical University, Weifang, Shandong, China
| | - Pengtao Liu
- School of Basic Medical Science, Shandong Second Medical University, Weifang, Shandong, China
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Khesali F, Yousefi A, Ahmadi SAY, Nekouian R. Investigation of Some Long Noncoding RNAs (LncRNAs) in Pediatric Inflammatory Bowel Disease (IBD): An Iranian Study. Biochem Res Int 2025; 2025:8879418. [PMID: 40191802 PMCID: PMC11972125 DOI: 10.1155/bri/8879418] [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: 05/31/2024] [Accepted: 03/13/2025] [Indexed: 04/09/2025] Open
Abstract
Introduction: According to the importance of long noncoding RNAs (LncRNA) in the pathogenesis of inflammatory bowel disease (IBD) and also the lack of study for pediatric IBD in this regard, we investigated the expression of a selected panel of LncRNAs in Iranian pediatric cases of IBD compared to adult cases and healthy samples. Methods: In this gene expression study, blood samples were taken from the three groups of pediatric IBD cases, adult IBD cases, and pediatric healthy samples (for gene expression calibration). The investigated LncRNAs were UCA1, CCAT, IFNG-AS1, and CDKN2B. Real-time PCR was used and fold changes (FCs) were reported. Results: A total of 50 individuals were studied including 28 cases of pediatric IBD, 12 cases of controls, and 10 cases of adult IBD. UCA1 showed upregulation in adult IBD (FC = 10.56, p = 0.007). CCAT showed downregulations for pediatric IBD (FC = 0.01, p < 0.001) and adult IBD (FC = 0.10, p = 0.039). IFNG-AS1 showed downregulation in pediatric IBD (FC < 0.01, p < 0.001). CDKN2B showed upregulation in pediatric IBD (FC = 17.39, p < 0.001). The results were in contrast with the literature. Conclusion: It seems that these LncRNAs may have different roles in pediatric IBD. Further studies are needed on pediatric cases of IBD.
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Affiliation(s)
- Fatemeh Khesali
- Department of Medical Biotechnology, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Azizollah Yousefi
- Department of Pediatrics, Rasoul Akram Complex Clinical Research Development Center (RCRDC), School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Seyyed Amir Yasin Ahmadi
- Preventive Medicine and Public Health Research Center, Psychosocial Health Research Institute, Iran University of Medical Sciences, Tehran, Iran
| | - Reza Nekouian
- Pediatric Growth and Development Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
- Mehresoheila Cancer Charity, Karaj, Alborz, Iran
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Calcaterra V, Penagini F, Rossi V, Abbattista L, Bianchi A, Turzi M, Cococcioni L, Zuccotti G. Thyroid disorders and inflammatory bowel disease: an association present in adults but also in children and adolescents. Front Endocrinol (Lausanne) 2025; 16:1425241. [PMID: 39968296 PMCID: PMC11832402 DOI: 10.3389/fendo.2025.1425241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 01/13/2025] [Indexed: 02/20/2025] Open
Abstract
Inflammatory bowel diseases (IBD) represent chronic inflammatory multisystemic disorders that primarily involve the gastrointestinal tract. Patients with ulcerative colitis (UC) and Crohn's disease (CD) exhibit a higher prevalence of thyroid disorders compared to the general population. The aim of this review is to summarize the literature on concomitant IBD and thyroid disorders, specifically autoimmune thyroid diseases such as Graves' disease (GD) and Hashimoto's thyroiditis (HT), as well as thyroid cancer, with a focus on children and adolescents. We provide an overview of the age-related differences between children and adults in the prevalence of this association. Literature shows that relatively few studies have been conducted on this subject in pediatric populations. The etiopathogenetic similarities between IBD and autoimmune thyroiditis are undeniable. Nevertheless, current data does not indicate a unanimous association between GD and HT and chronic IBD (both CD and UC). Although evidence suggests a potential association between IBD and thyroid cancer, particularly papillary thyroid cancer, the precise nature of this relationship varies across studies and is influenced by multiple factors. The limited information regarding the relationship between IBD and thyroid disorders in children highlights a significant knowledge gap. Since the thyroid plays a critical role in the pediatric population's development, it is essential to promptly recognize and treat thyroid diseases. A thyroid function monitoring and future research exploring the genetic and immunologic connections are essential to enhance our understanding of the interrelation between IBD and thyroid disorders.
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Affiliation(s)
- Valeria Calcaterra
- Pediatric and Adolescent Unit, Department of Internal Medicine, University of Pavia, Pavia, Italy
- Pediatric Department, Buzzi Children’s Hospital, Milano, Italy
| | | | - Virginia Rossi
- Pediatric Department, Buzzi Children’s Hospital, Milano, Italy
| | | | - Alice Bianchi
- Pediatric Department, Buzzi Children’s Hospital, Milano, Italy
| | | | | | - Gianvincenzo Zuccotti
- Pediatric Department, Buzzi Children’s Hospital, Milano, Italy
- Department of Biomedical and Clinical Science, University of Milan, Milano, Italy
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Hong R, Li Z, Li M, Dai Y. Hepatobiliary and pancreatic manifestations in inflammatory bowel disease: an umbrella review of meta-analyses. Therap Adv Gastroenterol 2025; 18:17562848241311165. [PMID: 39777137 PMCID: PMC11705336 DOI: 10.1177/17562848241311165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Accepted: 12/16/2024] [Indexed: 01/11/2025] Open
Abstract
Background Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), can affect the hepatobiliary system and pancreas, substantially impacting the life quality of patients. Objectives To evaluate the quality of evidence and comprehensively assess the validity of associations of IBD with hepatobiliary and pancreatic diseases. Design We performed an umbrella review of existing meta-analyses in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) recommendations. Data sources and methods We systematically searched PubMed, Embase, and Web of Science from inception to April 2024, to identify and appraise meta-analyses examining IBD and risk of hepatobiliary and pancreatic manifestations. Methodologic quality was assessed with A Measurement Tool to Assess Systematic Reviews (AMSTAR 2) and the strength of evidence was graded according to prespecified criteria. Results A total of 14 meta-analyses of observational studies were included. The strongest-validity evidence suggested the significant associations between IBD and risk of gallstones (odds ratio (OR) = 1.72; 95% confidence interval (CI) = 1.40-2.12) and acute pancreatitis (OR = 3.11; 95% CI = 2.93-3.30). Highly suggestive evidence indicated a significantly increased risk of hepatobiliary cancer in UC (incidence rate ratio (IRR) = 2.05; 95% CI = 1.52-2.76) and CD (IRR = 2.31; 95% CI = 1.25-4.28). In addition, highly suggestive evidence indicated that IBD was associated with portal venous system thrombosis. Suggestive evidence showed a significantly higher prevalence of primary sclerosing cholangitis, non-alcoholic fatty liver disease, autoimmune hepatitis, and autoimmune pancreatitis in IBD patients than in the general population. Conclusion The associations between IBD and multiple hepatobiliary and pancreatic disorders showed varying levels of evidence and magnitude of risk. Further high-quality primary studies are needed to identify IBD patients who are more at risk and would benefit the most from screening and prevention programs. Trial registration PROSPERO CRD42023451461.
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Affiliation(s)
- Runsheng Hong
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Zhixue Li
- Peking University Health Science Center, Beijing, China
| | - Meng Li
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Yun Dai
- Department of Gastroenterology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China
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Zamani M, Alizadeh-Tabari S, Murad MH, Singh S, Ananthakrishnan AN, Malekzadeh R, Talley NJ. Meta-analysis: Risk of lymphoma in patients with inflammatory bowel disease in population-based cohort studies. Aliment Pharmacol Ther 2024; 60:1264-1275. [PMID: 39310939 DOI: 10.1111/apt.18277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 07/22/2024] [Accepted: 09/02/2024] [Indexed: 10/25/2024]
Abstract
BACKGROUND There are inconsistencies in the results of the studies investigating the association between inflammatory bowel disease (IBD) and lymphoma. AIMS The aim of this study is to systematically appraise the risk of lymphoma development in patients with IBD. METHODS We searched Embase, PubMed and Scopus from inception to 30 April 2024 to identify population-based cohort studies that evaluated the risk of lymphoma in patients with IBD in comparison with those without IBD. We carried out random-effects meta-analyses and estimated pooled relative risks (RRs) with 95% confidence intervals (CIs). RESULTS We identified 23 eligible studies reporting 2078 lymphoma events in 656,731 patients with IBD. Patients with IBD had 30% higher odds of lymphoma (RR = 1.30 [95% CI: 1.21-1.40]). The risk of developing both Hodgkin's lymphoma (nine studies, RR = 1.29 [95% CI: 1.06-1.53]) and non-Hodgkin's lymphoma (16 studies, RR = 1.31 [95% CI: 1.20-1.42]) was increased in patients with IBD (p for interaction = 0.881). The increased risk of lymphoma was observed in both Crohn's disease (17 studies, RR = 1.54 [95% CI: 1.27-1.80]) and ulcerative colitis (20 studies, RR = 1.22 [95% CI: 1.09-1.35]) (p for interaction = 0.026). Meta-regression demonstrated that mean age of patients, study year, mean study follow-up duration, and percentages of immunomodulators and biologics use did not influence study outcome. CONCLUSIONS The risk of lymphoma is only modestly increased in patients with IBD, with Crohn's disease having a slightly higher risk than ulcerative colitis. In IBD, there appears to be no difference between the risks of Hodgkin's and non-Hodgkin's lymphoma.
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Affiliation(s)
- Mohammad Zamani
- Digestive Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Shaghayegh Alizadeh-Tabari
- Digestive Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Hassan Murad
- Kern Center for the Science of Healthcare Delivery Research, Mayo Clinic, Rochester, Minnesota, USA
| | - Siddharth Singh
- Division of Gastroenterology, and Division of Biomedical Informatics, University of California san Diego, La Jolla, California, USA
| | - Ashwin N Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Reza Malekzadeh
- Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Nicholas J Talley
- School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia
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Murthy SK, Tandon P, Matthews P, Ahmed F, Pugliese M, Taljaard M, Kaplan GG, Coward S, Bernstein C, Benchimol EI, Kuenzig ME, Targownik LE, Singh H. A Population-Based Matched Cohort Study of Digestive System Cancer Incidence and Mortality in Individuals With and Without Inflammatory Bowel Disease. Am J Gastroenterol 2024; 119:2275-2287. [PMID: 38916226 PMCID: PMC11524629 DOI: 10.14309/ajg.0000000000002900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 06/12/2024] [Indexed: 06/26/2024]
Abstract
INTRODUCTION To study digestive system cancer risks in individuals with inflammatory bowel diseases (IBDs) in the biologic era. METHODS We used population-level administrative and cancer registry data from Ontario, Canada, (1994-2020) to compare people with IBD to matched controls (1:10 by sex and birth year) on trends in age-sex standardized cancer incidence and risk ratios of incident cancers and cancer-related deaths. RESULTS Among 110,919 people with IBD and 1,109,190 controls, colorectal cancer incidence (per 100,000 person-years) declined similarly in people with ulcerative colitis (average annual percentage change [AAPC] -1.81; 95% confidence interval [CI] -2.48 to -1.156) and controls (AAPC -2.79; 95% CI -3.44 to -2.14), while small bowel cancer incidence rose faster in those with Crohn's disease (AAPC 9.68; 95% CI 2.51-17.3) than controls (AAPC 3.64; 95% CI 1.52-5.80). Extraintestinal digestive cancer incidence rose faster in people with IBD (AAPC 3.27; 95% CI 1.83-4.73) than controls (AAPC -1.87; 95% CI -2.33 to -1.42), particularly for liver (IBD AAPC 8.48; 95% CI 4.11-13.1) and bile duct (IBD AAPC 7.22; 95% CI 3.74-10.8) cancers. Beyond 2010, the incidences (and respective mortality rates) of colorectal (1.60; 95% CI 1.46-1.75), small bowel (4.10; 95% CI 3.37-4.99), bile duct (2.33; 95% CI 1.96-2.77), and pancreatic (1.19; 95% CI 1.00-1.40) cancers were higher in people with IBD. DISCUSSION Cancer incidence is declining for colorectal cancer and rising for other digestive cancers in people with IBD. Incidence and mortality remain higher in people with IBD than controls for colorectal, small bowel, bile duct, and pancreatic cancers.
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Affiliation(s)
- Sanjay K. Murthy
- Department of Medicine and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
- The Ottawa Hospital, IBD Centre, Ottawa, Ontario, Canada
- Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- ICES, Toronto, Canada
| | - Parul Tandon
- ICES, Toronto, Canada
- Division of Gastroenterology and Hepatology, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | | | - Faria Ahmed
- Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | | | - Monica Taljaard
- Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- ICES, Toronto, Canada
| | - Gilaad G. Kaplan
- Department of Medicine and Community Health Sciences, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Stephanie Coward
- Department of Medicine and Community Health Sciences, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Charles Bernstein
- University of Manitoba IBD Clinical and Research Centre, Winnipeg, Manitoba, Canada
- Departments of Internal Medicine and Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Eric I. Benchimol
- ICES, Toronto, Canada
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Paediatrics and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
| | - M. Ellen Kuenzig
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Laura E. Targownik
- Mount Sinai Hospital IBD Centre, Toronto, Ontario, Canada
- Division of Gastroenterology and Hepatology, University of Toronto, Ontario, Canada
| | - Harminder Singh
- University of Manitoba IBD Clinical and Research Centre, Winnipeg, Manitoba, Canada
- Departments of Internal Medicine and Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- Paul Albrechtsen Research Institute CancerCare Manitoba, Winnipeg, Manitoba, Canada
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7
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Adamina M, Minozzi S, Warusavitarne J, Buskens CJ, Chaparro M, Verstockt B, Kopylov U, Yanai H, Vavricka SR, Sigall-Boneh R, Sica GS, Reenaers C, Peros G, Papamichael K, Noor N, Moran GW, Maaser C, Luglio G, Kotze PG, Kobayashi T, Karmiris K, Kapizioni C, Iqbal N, Iacucci M, Holubar S, Hanzel J, Sabino JG, Gisbert JP, Fiorino G, Fidalgo C, Ellu P, El-Hussuna A, de Groof J, Czuber-Dochan W, Casanova MJ, Burisch J, Brown SR, Bislenghi G, Bettenworth D, Battat R, Atreya R, Allocca M, Agrawal M, Raine T, Gordon H, Myrelid P. ECCO Guidelines on Therapeutics in Crohn's Disease: Surgical Treatment. J Crohns Colitis 2024; 18:1556-1582. [PMID: 38878002 DOI: 10.1093/ecco-jcc/jjae089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Indexed: 07/28/2024]
Abstract
This article is the second in a series of two publications on the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of prior ECCO Guidelines.
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Affiliation(s)
- Michel Adamina
- Department of Surgery, Cantonal Hospital of Fribourg & Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
| | - Silvia Minozzi
- Department of Epidemiology, Lazio Regional Health Service, Rome, Italy
| | | | | | - Maria Chaparro
- Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-Princesa], Universidad Autónoma de Madrid [UAM], Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | - Bram Verstockt
- Department Gastroenterology & Hepatology, University Hospitals Leuven, KU Leuven, Belgium
- Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Uri Kopylov
- Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel
| | - Henit Yanai
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Stephan R Vavricka
- Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland
| | - Rotem Sigall-Boneh
- Pediatric Gastroenterology and Nutrition Unit, The E. Wolfson Medical Center, Holon, Israel
- Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology and Metabolism, University of Amsterdam, Amsterdam, The Netherlands
| | - Giuseppe S Sica
- Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology and Metabolism, University of Amsterdam, Amsterdam, The Netherlands
- Department of Surgery, Università Tor Vergata, Roma, Italy
| | | | - Georgios Peros
- Department of Surgery, Cantonal Hospital Winterthur, Winterthur, Switzerland
| | - Konstantinos Papamichael
- Center for Inflammatory Bowel Diseases, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Nurulamin Noor
- Department of Medicine, University of Cambridge, Cambridge, UK
| | - Gordon William Moran
- National Institute of Health Research Nottingham Biomedical Research Centre, University of Nottingham and Nottingham University Hospitals, Nottingham, UK
- Translational Medical Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK
| | - Christian Maaser
- Outpatients Department of Gastroenterology, University Teaching Hospital Lueneburg, Lueneburg, Germany
| | - Gaetano Luglio
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | - Paulo Gustavo Kotze
- Health Sciences Postgraduate Program, Pontificia Universidade Católica do Paraná [PUCPR], Curitiba, Brazil
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | | | | | - Nusrat Iqbal
- Department of Surgery, Worcestershire Acute Hospitals NHS Trust, Worcester, UK
| | - Marietta Iacucci
- APC Microbiome Ireland, College of Medicine and Health, University College of Cork, Cork, Ireland
| | - Stefan Holubar
- Department of Colon & Rectal Surgery, Cleveland Clinic, Cleveland, OH, USA
| | - Jurij Hanzel
- Department of Gastroenterology, University Medical Centre Ljubljana, Ljubljana, Slovenia
- Department of of Internal Medicine, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - João Guedelha Sabino
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Javier P Gisbert
- Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-Princesa], Universidad Autónoma de Madrid [UAM], Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | | | - Catarina Fidalgo
- Division of Gastroenterology, Hospital Beatriz Ângelo, Loures Division of Gastroenterology, Hospital da Luz, Lisboa, Portugal
| | - Pierre Ellu
- Division of Gastroenterology, Mater Dei Hospital, l-Msida, Malta
| | - Alaa El-Hussuna
- OpenSourceResearch Organization [OSRC.Network], Aalborg, Denmark
| | - Joline de Groof
- Colorectal Surgery, Royal Surrey NHS Foundation Trust, Guildford, UK
| | - Wladyslawa Czuber-Dochan
- Florence Nightingale Faculty of Nursing-Midwifery and Palliative Care, King's College London, London, UK
| | - María José Casanova
- Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-Princesa], Universidad Autónoma de Madrid [UAM], Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | - Johan Burisch
- Gastrounit, Medical Division, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
| | | | | | - Dominik Bettenworth
- CED Schwerpunktpraxis, Münster and Medical Faculty of the University of Münster, Münster, Germany
| | - Robert Battat
- Division of Gastroenterology, Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada
| | - Raja Atreya
- First Department of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
| | - Mariangela Allocca
- IRCCS Hospital San Raffaele and University Vita-Salute San Raffaele, Gastroenterology and Endoscopy, Milan, Italy
| | - Manasi Agrawal
- Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Center for Molecular Prediction of Inflammatory Bowel Disease [PREDICT], Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - Tim Raine
- Department of Gastroenterology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Hannah Gordon
- Translational Gastroenterology and Liver Unit, Gastroenterology Office, University of Oxford, Oxford, UK
| | - Pär Myrelid
- Department of Surgery and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
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8
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Chen P, Wang Y, Xiong Z, Luo T, Lai Y, Zhong H, Peng S, Zhuang R, Li K, Huang H. Association between autoimmunity-related disorders and prostate cancer: A Mendelian randomization study. CANCER PATHOGENESIS AND THERAPY 2024; 2:292-298. [PMID: 39371096 PMCID: PMC11447306 DOI: 10.1016/j.cpt.2024.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Revised: 03/12/2024] [Accepted: 03/20/2024] [Indexed: 10/08/2024]
Abstract
Background Although many epidemiological studies and meta-analyses have reported an association between autoimmune disorders and prostate cancer, none has reported a clear correlation or the direction of the association. The purpose of our study was to explore the potential relationship between autoimmunity-related disorders and prostate cancer using Mendelian randomization (MR). Methods We retrieved literature from PubMed using the keywords "autoimmune disorder" AND "prostate cancer" to find more clues on the correlation between prostate cancer and autoimmunity-related disorder. Based on this literature search, we selected 16 autoimmunity-related disorders that had genome-wide association study (GWAS) data and may be associated with prostate cancer. The inverse variance weighting (IVW) method was applied as our primary analysis for two-sample MR and multivariate MR analysis to estimate the odds ratio (OR) and 95% confidence interval (CI). We further verified the robustness of our conclusions using a series of sensitivity analyses. Results The autoimmunity-related diseases selected include rheumatoid arthritis, ankylosing spondylitis, coxarthrosis, gonarthrosis, Crohn's disease, ulcerative colitis, irritable bowel syndrome, celiac disease, primary sclerosing cholangitis, asthma, type 1 diabetes, systemic lupus erythematosus, multiple sclerosis, autoimmune hyperthyroidism, psoriatic arthropathies, and polymyalgia rheumatica. The results of inverse variance weighting (IVW suggested that six diseases were associated with the development of prostate cancer. The three diseases that may increase the risk of prostate cancer are rheumatoid arthritis (P = 0.001), coxarthrosis (P < 0.001), and gonarthrosis (P = 0.008). The three possible protective factors against prostate cancer are primary sclerosing cholangitis (P = 0.001), autoimmune hyperthyroidism (P = 0.011), and psoriatic arthropathies (P = 0.001). Horizontal pleiotropy was not observed in the MR-Egger test. Conclusions Our findings provide predictive genetic evidence for an association between autoimmune disorders and prostate cancer. Further research is needed to explore the underlying mechanisms of comorbidities at the molecular level.
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Affiliation(s)
- Peixian Chen
- Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China
| | - Yue Wang
- National Institutes for Food and Drug Control, Beijing 102629, China
| | - Zhi Xiong
- Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China
| | - Tianlong Luo
- Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China
| | - Yiming Lai
- Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China
| | - Haitao Zhong
- Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China
| | - Shirong Peng
- Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China
| | - Ruilin Zhuang
- Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China
| | - Kaiwen Li
- Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China
| | - Hai Huang
- Department of Urology, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong Provincial Clinical Research Center for Urological Diseases, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China
- Department of Urology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, Guangdong 511518, China
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9
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Singh A, Khanna T, Mahendru D, Kahlon J, Kumar V, Sohal A, Yang J. Insights into renal and urological complications of inflammatory bowel disease. World J Nephrol 2024; 13:96574. [PMID: 39351187 PMCID: PMC11439091 DOI: 10.5527/wjn.v13.i3.96574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 07/01/2024] [Accepted: 07/15/2024] [Indexed: 09/19/2024] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic condition characterized by immune-mediated inflammation in the gastrointestinal tract, which follows a relapsing and remitting course. Apart from affecting the gastrointestinal tract, IBD also has extra-intestinal manifestations (EIMs). While the etiology of extraintestinal manifestation remains unclear, it is theorized to be based on immunological responses influenced by genetic factors. Renal involvement is one of the EIMs observed in ulcerative colitis and Crohn's disease. The renal manifestations in IBD patients encompass a range of conditions including nephrolithiasis, amyloidosis, tubulointerstitial nephritis, glomerulonephritis (GN), obstructive pathologies, and chronic kidney disease (CKD). The incidence of CKD in IBD patients varies from 5%-15%. The decline in renal function can stem from various factors such as direct inflammatory damage to the kidneys leading to glomerular or tubular injury, or from complications like recurrent stones, amyloidosis, or GN. Additionally, nephrotoxic medications used in treating IBD, such as TNF-α inhibitors, calcineurin inhibitors, and aminosalicylates, can exacerbate the decline in renal function. Currently, there is a lack of consensus regarding these patients' screening and renal function monitoring. This review aims to assess the existing literature on the different renal complications among individuals with IBD, shedding light on their pathophysiology and management.
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Affiliation(s)
- Anmol Singh
- Department of Medicine, Tristar Centennial Medical Center, Nashville, TN 37203, United States
| | - Tejasvini Khanna
- Department of Medicine, Maulana Azad Medical College, New Delhi 110002, India
| | - Diksha Mahendru
- Department of Medicine, Dayanand Medical College and Hospital, Ludhiana 141001, Punjab, India
| | - Jasraj Kahlon
- Department of Internal Medicine, Abrazo Medical Center, Phoenix, AZ 85015, United States
| | - Vikash Kumar
- Department of Medicine, The Brooklyn Hospital Center, Brooklyn, NY 11201, United States
| | - Aalam Sohal
- Department of Hepatology, Liver Institute Northwest, Seattle, WA 98105, United States
| | - Juliana Yang
- Division of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, TX 77555, United States
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10
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Li R, Luo W, Chen X, Zeng Q, Yang S, Wang P, Hu J, Chen A. An observational and genetic investigation into the association between psoriasis and risk of malignancy. Nat Commun 2024; 15:7952. [PMID: 39261450 PMCID: PMC11391051 DOI: 10.1038/s41467-024-51824-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Accepted: 08/16/2024] [Indexed: 09/13/2024] Open
Abstract
The relationship between psoriasis and site-specific cancers remains unclear. Here, we aim to investigate whether psoriasis is causally associated with site-specific cancers. We use observational and genetic data from the UK Biobank, obtaining GWAS summary data, eQTL analysis data, TCGA data, and GTEx data from public datasets. We perform PheWAS, polygenic risk score analysis, and one-sample and two-sample Mendelian randomization analyses to investigate the potential causal associations between psoriasis and cancers. In the unselected PheWAS analysis, psoriasis is associated with higher risks of 16 types of cancer. Using one-sample Mendelian randomization analyses, it is found that genetically predicted psoriasis is associated with higher risks of anal canal cancer, breast cancer, follicular non-Hodgkin's lymphoma and nonmelanoma skin cancer in women; and lung cancer and kidney cancer in men. Our two-sample Mendelian randomization analysis indicates that psoriasis is causally associated with breast cancer and lung cancer. Gene annotation shows that psoriasis-related genes, such as ERAP1, are significantly different in lung and breast cancer tissues. Taken together, clinical attention to lung cancer and breast cancer may be warranted among patients with psoriasis.
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Affiliation(s)
- Ruolin Li
- Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Wenjin Luo
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiangjun Chen
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qinglian Zeng
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Shumin Yang
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ping Wang
- Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jinbo Hu
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
| | - Aijun Chen
- Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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11
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Han J, Zhao Y, Canney M, Atiquzzaman M, Keown P, Levin A, Barbour S. Are patients with primary glomerular disease at increased risk of malignancy? Nephrol Dial Transplant 2024; 39:910-919. [PMID: 38070875 DOI: 10.1093/ndt/gfad261] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Indexed: 06/01/2024] Open
Abstract
Over the past decade, several observational studies and case series have provided evidence suggesting a connection between glomerular diseases and the development of malignancies, with an estimated risk ranging from 5 to 11%. These malignancies include solid organ tumours as well as haematologic malignancies such as lymphoma and leukaemia. However, these risk estimates are subject to several sources of bias, including unmeasured confounding from inadequate exploration of risk factors, inclusion of glomerular disease cases that were potentially secondary to an underlying malignancy, misclassification of glomerular disease type and ascertainment bias arising from an increased likelihood of physician encounters compared with the general population. Consequently, population-based studies that accurately evaluate the cancer risk in glomerular disease populations are lacking. While it is speculated that long-term use of immunosuppressive medications and glomerular disease activity measured by proteinuria and estimated glomerular filtration rate may be associated with cancer risk in patients with glomerular disease, the independent role of these risk factors remains largely unknown. The presence of these knowledge gaps could lead to a lack of awareness of cancer as a potential chronic complication of glomerular disease, underutilization of routine screening practices in clinical care that allow early diagnosis and treatment of malignancies and underrecognition of modifiable risk factors to decrease the risk of de novo malignancies over time. This review summarizes the current evidence on the risk of cancer in patients with glomerular diseases, explores the limitations of prior studies and discusses methodological challenges and potential solutions for obtaining accurate estimates of cancer risk and identifying modifiable risk factors unique to GN populations.
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Affiliation(s)
- Jialin Han
- Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Yinshan Zhao
- School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Mark Canney
- Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Mohammad Atiquzzaman
- Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Paul Keown
- Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Adeera Levin
- Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- BC Renal, Provincial Health Services Authority, Vancouver, British Columbia, Canada
| | - Sean Barbour
- Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- BC Renal, Provincial Health Services Authority, Vancouver, British Columbia, Canada
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12
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Romano L, Napolitano L, Crocetto F, Sciorio C, Sio MD, Miranda A, Romano M, Priadko K. Prostate and gut: Any relationship? A narrative review on the available evidence and putative mechanisms. Prostate 2024; 84:513-524. [PMID: 38353479 DOI: 10.1002/pros.24675] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 12/26/2023] [Accepted: 01/30/2024] [Indexed: 03/22/2024]
Abstract
BACKGROUND Gut microbiome is a community of microorganisms that lives in the human intestine and exerts various functions on the host, including metabolic, immunoregulatory, and control over cell proliferation. Gut microbiome alterations have been associated with various pathological conditions, such as diabetes mellitus, obesity, and cardiovascular diseases. Gut-prostate axis is explained by the association between gut microbiome quantitative and functional alterations along with increased intestinal epithelial permeability with prostatediseases. However, the pathophysiological mechanisms and clinical importance of this association are not completely clarified yet. METHODS We conducted a narrative review of the most relevant articles in the Medline (US National Library of Medicine, Bethesda, MD, USA), Scopus (Elsevier, Amsterdam, The Netherlands) and Web of Science Core Collection (Thomson Reuters, Toronto, ON, Canada) databases. No chronological restrictions were applied, and the most related papers published until December 2023 were included. RESULTS Gut microbiota (GM) and its metabolites are capable of modifying host androgen level, as well as prostate cancer (PCa) therapy response. Moreover, patients with inflammatory bowel disease have higher rates of prostatitis-like symptoms and a potential risk of developing PCa. CONCLUSIONS There is evidence that interventions on the GM and its metabolites have a high potential to serve as diagnostic and therapeutic tools for prostate diseases, including PCa.
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Affiliation(s)
- Lorenzo Romano
- Department of Neurosciences, Reproductive Sciences and Odontostomatology and Urology Unit, Federico II University, Naples, Italy
- Department of Woman, Child and General and Specialized Surgery, Unit of Urology, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Luigi Napolitano
- Department of Neurosciences, Reproductive Sciences and Odontostomatology and Urology Unit, Federico II University, Naples, Italy
| | - Felice Crocetto
- Department of Neurosciences, Reproductive Sciences and Odontostomatology and Urology Unit, Federico II University, Naples, Italy
| | | | - Marco De Sio
- Department of Woman, Child and General and Specialized Surgery, Unit of Urology, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Agnese Miranda
- Department of Precision Medicine and Hepatogastroenterology Unit, University of Campania "L. Vanvitelli", Naples, Italy
| | - Marco Romano
- Department of Precision Medicine and Hepatogastroenterology Unit, University of Campania "L. Vanvitelli", Naples, Italy
| | - Kateryna Priadko
- Department of Precision Medicine and Hepatogastroenterology Unit, University of Campania "L. Vanvitelli", Naples, Italy
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13
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Mao YQ, Sun SP, Lv B, Fan YH. Progress in understanding of relationship between use of biological agents and risk of malignant tumors in patients with inflammatory bowel disease. WORLD CHINESE JOURNAL OF DIGESTOLOGY 2024; 32:221-227. [DOI: 10.11569/wcjd.v32.i3.221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/29/2024]
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14
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Tassone D, Basnayake C, Wright E, Lust M, Kamm MA, Niewiadomski O, Schulberg J, Flanagan E, Samyue T, Fry S, Malcolm R, Stanley A, Thompson AJ, Connell WR, Ding NS. Risk factors for malignancy and serious infection in patients with inflammatory bowel disease: a retrospective analysis. Intern Med J 2024; 54:446-454. [PMID: 37255273 DOI: 10.1111/imj.16141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 05/18/2023] [Indexed: 06/01/2023]
Abstract
BACKGROUND Patients with inflammatory bowel disease (IBD) are at increased risk of malignancy and infection compared to the general population. AIMS We aim to identify risk factors for malignancy or serious infection in our IBD cohort. METHODS Patients with IBD from a single tertiary referral centre were included. Demographic and clinical details, including immunosuppressant exposure, were collected and medical records retrospectively screened for adverse events, including malignancy or infection requiring hospitalisation. Logistic regression was used to evaluate risk factors for adverse events. RESULTS Five hundred and forty-nine patients with IBD (340 Crohn disease (CD) and 209 ulcerative colitis (UC)) were studied. Forty-eight malignancies, including 39 (81.3%) non-melanoma skin cancers, 3 (6.3%) haematologic malignancies and 6 (15.4%) solid-organ malignancies, were identified, and 92 cases of serious infection were detected. IBD duration (odds ratio (OR) = 1.08; 95% confidence interval (CI) = 1.03-1.13) and ileocolonic CD (OR = 4.96; 95% CI = 1.13-21.71) were associated with increased odds of overall cancer. Compared with patients not previously exposed to the given class of immunosuppression assessed, the development of overall malignancy was not higher with thiopurine exposure (OR = 1.00; 95% CI = 0.50-2.24) or anti-tumour necrosis factor-alpha (TNF-α) exposure (OR = 0.78; 95% CI = 0.37-1.64). Similarly, compared with patients not exposed, infection risk was not affected by thiopurine (OR = 0.74; 95% CI = 0.46-1.20) or anti-TNF exposure (OR = 0.60; 95% CI = 0.38-0.95). CONCLUSIONS Factors including ileocolonic CD and increasing IBD duration were associated with higher malignancy risk in this cohort. Compared with non-exposure, patients exposed to thiopurines were not at increased risk of malignancy or serious infection. Similarly, patients exposed to anti-TNF treatment did not experience increased rates of malignancy or serious infection compared to patients not exposed to this treatment.
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Affiliation(s)
- Daniel Tassone
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Chamara Basnayake
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Emily Wright
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Mark Lust
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Michael A Kamm
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Ola Niewiadomski
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Julien Schulberg
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Emma Flanagan
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Tamie Samyue
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Stephanie Fry
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Ruth Malcolm
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Annalise Stanley
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Alexander J Thompson
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - William R Connell
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Nik S Ding
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
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15
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Viola A, Fiorino G, Costantino G, Fries W. Epidemiology and clinical course of late onset inflammatory bowel disease. Minerva Gastroenterol (Torino) 2024; 70:52-58. [PMID: 34057332 DOI: 10.23736/s2724-5985.21.02890-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
With the increasing age of the general population in developed countries, the management of several chronic diseases becomes more and more complex due to comorbidities. Some, especially inflammatory bowel diseases, formerly believed to belong to the young adult population, have now been recognized as being present at disease onset also in the ageing population, representing medical challenges different from those in the younger population. In the past few years, knowledge on this special older population has increased, changing initial beliefs concerning epidemiology and course of disease. In the present review, we addressed the most recent evidence concerning their current incidence compared with other age groups, their clinical course, potential risk factors for the development of late-onset IBDs, associated diseases, and cancer risk beyond therapy-related neoplasias.
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Affiliation(s)
- Anna Viola
- Gastroenterology and Clinical Unit for Chronic Bowel Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy -
| | - Gionata Fiorino
- Department of Gastroenterology, IBD Center, Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Giuseppe Costantino
- Gastroenterology and Clinical Unit for Chronic Bowel Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Walter Fries
- Gastroenterology and Clinical Unit for Chronic Bowel Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
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16
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Kaneko M, Kanatani Y, Sato H, Sano M, Teramura E, Imai J, Fujisawa M, Matsushima M, Suzuki H. Prognostic Factors in Prostate Cancer Associated with Ulcerative Colitis. J Clin Med 2024; 13:1392. [PMID: 38592255 PMCID: PMC10932459 DOI: 10.3390/jcm13051392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 02/17/2024] [Accepted: 02/27/2024] [Indexed: 04/10/2024] Open
Abstract
Ulcerative colitis (UC) has been associated with increased prostate cancer (PCa) risk. However, the mechanisms underlying UC and increased PCa risk remain unclear, and research on this topic is scarce in Japan. We have investigated whether UC is associated with PCa risk in the Japanese population and the risk factors related to PCa among older UC patients. This retrospective single-center cohort study was conducted between January 2010 and April 2022. A total of 68 cases were analyzed, and 9 cases of PCa were observed (13.2%). PCa occurred more frequently in the adult-onset group (8/40, 20.0%) than in the older-onset group with UC (1/28; 3.57%). No significant differences were observed between immunosuppressive therapies and PCa in patients, excluding those with pancolitis-type UC. PCa occurred more frequently in the pancolitis type, and the biologics group had no PCa cases, but the difference was not statistically significant (p = 0.07). This study suggests that pancolitis type and UC onset in middle-aged patients may be risk factors and found that biologics potentially suppress PCa development.
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Affiliation(s)
- Motoki Kaneko
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Japan; (M.K.); (H.S.); (M.S.)
| | - Yasuhiro Kanatani
- Department of Clinical Pharmacology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Japan
| | - Hirohiko Sato
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Japan; (M.K.); (H.S.); (M.S.)
| | - Masaya Sano
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Japan; (M.K.); (H.S.); (M.S.)
| | - Erika Teramura
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Japan; (M.K.); (H.S.); (M.S.)
| | - Jin Imai
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Japan; (M.K.); (H.S.); (M.S.)
- Department of Clinical Health Science, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Japan
| | - Mia Fujisawa
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Japan; (M.K.); (H.S.); (M.S.)
| | - Masashi Matsushima
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Japan; (M.K.); (H.S.); (M.S.)
| | - Hidekazu Suzuki
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Tokai University, 143 Shimokasuya, Isehara 259-1193, Japan; (M.K.); (H.S.); (M.S.)
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17
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Yu C, Xu J, Xu S, Huang Y, Tang L, Zeng X, Yu T, Chen W, Sun Z. Appraising the causal association between Crohn's disease and breast cancer: a Mendelian randomization study. Front Oncol 2024; 13:1275913. [PMID: 38406175 PMCID: PMC10884953 DOI: 10.3389/fonc.2023.1275913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 12/27/2023] [Indexed: 02/27/2024] Open
Abstract
Background Previous research has indicated that there may be a link between Crohn's disease (CD) and breast cancer (BC), but the causality remains unclear. This study aimed to investigate the causal association between CD and BC using Mendelian randomization (MR) analysis. Methods The summary data for CD (5,956 cases/14,927 controls) was obtained from the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). And the summary data for BC (122,977 cases/105,974 controls) was extracted from the Breast Cancer Association Consortium (BCAC). Based on the estrogen receptor status, the cases were classified into two subtypes: estrogen receptor-positive (ER+) BC and estrogen receptor-negative (ER-) BC. We used the inverse variance weighted method as the primary approach for two-sample MR. MR-PRESSO method was used to rule out outliers. Heterogeneity and pleiotropy tests were carried out to improve the accuracy of results. Additionally, multivariable MR was conducted by adjusting for possible confounders to ensure the stability of the results. Results The two-sample MR indicated that CD increased the risks of overall (OR: 1.020; 95% CI: 1.010-1.031; p=0.000106), ER+ (OR: 1.019; 95%CI: 1.006-1.034; p=0.006) and ER- BC (OR: 1.019; 95%CI: 1.000-1.037; p=0.046) after removal of outliers by MR-PRESSO. This result was reliable in the sensitivity analysis, including Cochran's Q and MR-Egger regression. In multivariate MR analyses, after adjusting for smoking and drinking separately or concurrently, the positive association between CD and the risks of overall and ER+ BC remained, but it disappeared in ER- BC. Furthermore, reverse MR analysis suggested that BC did not have a significant impact on CD risk. Conclusion Our findings provide evidence for a possible positive association between CD and the risk of BC. However, further studies are needed to fully understand the underlying mechanisms and establish a stronger causal relationship.
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Affiliation(s)
- Chengdong Yu
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Jiawei Xu
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Siyi Xu
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Yanxiao Huang
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Lei Tang
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Xiaoqiang Zeng
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Tenghua Yu
- Department of Breast Surgery, Jiangxi Cancer Hospital, Nanchang, China
| | - Wen Chen
- Department of Breast Surgery, Jiangxi Cancer Hospital, Nanchang, China
| | - Zhengkui Sun
- Department of Breast Surgery, Jiangxi Cancer Hospital, Nanchang, China
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18
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Yu C, Xu J, Xu S, Tang L, Han Q, Zeng X, Huang Y, Yu T, Sun Z. Exploring genetic associations of Crohn's disease and ulcerative colitis with extraintestinal cancers in European and East Asian populations. Front Immunol 2024; 15:1339207. [PMID: 38404590 PMCID: PMC10885353 DOI: 10.3389/fimmu.2024.1339207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 01/19/2024] [Indexed: 02/27/2024] Open
Abstract
Background Previous studies have reported associations of Crohn's disease (CD) and ulcerative colitis (UC) with the risks of extraintestinal cancers, but the causality remains unclear. Methods Using genetic variations robustly associated with CD and UC extracted from genome-wide association studies (GWAS) as instrumental variables. Nine types of extraintestinal cancers of European and Asian populations were selected as outcomes. We used the inverse variance weighted method as the primary approach for two-sample Mendelian randomization analysis. Sensitivity analyses were carried out to evaluate the reliability of our findings. Results In the European population, we found that CD showed a potential causal relationship with pancreatic cancer (OR: 1.1042; 95% CI: 1.0087-1.2088; P=0.0318). Meanwhile, both CD (outliers excluded: OR: 1.0208; 95% CI: 1.0079-1.0339; P=0.0015) and UC (outliers excluded: OR: 1.0220; 95% CI: 1.0051-1.0393; P=0.0108) were associated with a slight increase in breast cancer risk. Additionally, UC exhibited a potential causal effect on cervical cancer (outliers excluded: OR: 1.1091; 95% CI: 1.0286-1.1960; P=0.0071). In the East Asian population, CD had significant causal effects on pancreatic cancer (OR: 1.1876; 95% CI: 1.0741-1.3132; P=0.0008) and breast cancer (outliers excluded: OR: 0.9452; 95% CI: 0.9096-0.9822; P=0.0040). For UC, it exhibited significant causal associations with gastric cancer (OR: 1.1240; 95% CI: 1.0624-1.1891; P=4.7359×10-5), bile duct cancer (OR: 1.3107; 95% CI: 1.0983-1.5641; P=0.0027), hepatocellular carcinoma (OR: 1.2365; 95% CI: 1.1235-1.3608; P=1.4007×10-5) and cervical cancer (OR: 1.3941; 95% CI: 1.1708-1.6599; P=0.0002), as well as a potential causal effect on lung cancer (outliers excluded: OR: 1.1313; 95% CI: 1.0280-1.2449; P=0.0116). Conclusions Our study provided evidence that genetically predicted CD may be a risk factor for pancreatic and breast cancers in the European population, and for pancreatic cancer in the East Asian population. Regarding UC, it may be a risk factor for cervical and breast cancers in Europeans, and for gastric, bile duct, hepatocellular, lung, and cervical cancers in East Asians. Therefore, patients with CD and UC need to emphasize screening and prevention of site-specific extraintestinal cancers.
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Affiliation(s)
- Chengdong Yu
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Jiawei Xu
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Siyi Xu
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Lei Tang
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Qinyuan Han
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Xiaoqiang Zeng
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Yanxiao Huang
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Tenghua Yu
- Department of breast surgery, Jiangxi Cancer Hospital, Nanchang, China
| | - Zhengkui Sun
- Department of breast surgery, Jiangxi Cancer Hospital, Nanchang, China
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19
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Zhang H, Hu C, Zhang Z, Li P, Shen G, Sun J. Two-sample Mendelian randomization study reveals no causal relationship between inflammatory bowel disease and urological cancers. Front Genet 2023; 14:1275247. [PMID: 38188502 PMCID: PMC10771298 DOI: 10.3389/fgene.2023.1275247] [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: 08/09/2023] [Accepted: 12/06/2023] [Indexed: 01/09/2024] Open
Abstract
Background: The relationship between inflammatory bowel disease (IBD) and urological cancers has been identified in epidemiological and observational studies, while the causality remains uncertain. We examined whether IBD is causally associated with urological cancers in a Mendelian randomization (MR) study. Methods: The causal relationship between IBD, its main subtypes, and urological cancers was investigated using genome-wide association study data. To obtain more reliable conclusions, all outcomes were divided into training and validation sets. Eligible single-nucleotide polymorphisms were selected as instrumental variables based on MR analysis assumptions. The inverse variance-weighted (IVW) method was employed as the main method along with four other complementary methods. Results: In this two-sample MR study, no genetic evidence for the causal effect of IBD on urological cancers was found in either the training or validation sets using the IVW method. Similarly, we did not observe any significant association between Crohn's disease or ulcerative colitis and urological cancers. The results of the other methods are in accordance with those obtained using the IVW method. Conclusion: In this study, we confirmed that IBD is not a causal genetic risk factor for urological cancer in a European population.
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Affiliation(s)
- Haoyang Zhang
- Department of Urology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
| | - Can Hu
- Department of Urology, Suzhou Xiangcheng People’s Hospital, Suzhou, China
| | - Zhiyu Zhang
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Peng Li
- Department of Urology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
| | - Gang Shen
- Department of Urology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
| | - Jiale Sun
- Department of Urology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
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20
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Liu J, Wu P, Lai S, Wang J, Wang J, Zhang Y. Identifying possible hub genes and biological mechanisms shared between bladder cancer and inflammatory bowel disease using machine learning and integrated bioinformatics. J Cancer Res Clin Oncol 2023; 149:16885-16904. [PMID: 37740761 DOI: 10.1007/s00432-023-05266-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 08/08/2023] [Indexed: 09/25/2023]
Abstract
BACKGROUND Recent studies have shown that inflammatory bowel disease (IBD) is associated with bladder cancer (BC) incidence. But there is still a lack of understanding regarding its pathogenesis. Thus, this study aimed to identify potential hub genes and their important pathways and pathological mechanisms of interactions between IBD and BC using bioinformatics methods. METHODS The data from Gene Expression Omnibus (GEO) and the cancer genome atlas (TCGA) were analyzed to screen common differentially expressed genes (DEGs) between IBD and BC. The "clusterProfiler" package was used to analyze GO term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment in DEGs. After that, we conducted a weighted gene co-expression network analysis (WGCNA) on these DEGs to determine the vital modules and genes significantly related to BC. Protein-protein interaction (PPI) networks was used to identify hub genes. Further, the hub genes were used to develop a prognostic signature by Cox analysis. The validity of the ten hub DEGs was tested using three classification algorithms. Finally, we analyzed the microRNAs (miRNA)-mRNA, transcription factors (TFs)-mRNA regulatory network. RESULTS Positive regulation of organelle fission, chromosomal region, tubulin binding, and cell cycle signaling pathway were the major enriched pathways for the common DEGs. PPI networks identified three hub proteins (AURKB, CDK1, and CCNA2) with high connectivity. Three machine-learning classification algorithms based on ten hub genes performed well for IBD and BC (accuracy > 0.80). The robust predictive model based on the ten hub genes could accurately classify BC cases with various clinical outcomes. Based on the gene-TFs and gene-miRNAs network construction, 9 TFs and 6 miRNAs were identified as potential critical TFs and miRNAs. There are 13 drugs that interact with the hub gene based on gene-drug interaction analysis. CONCLUSIONS This study explored common gene signatures and the potential pathogenesis of IBD and BC. We revealed that an unbalanced immune response, cell cycle pathway, and neutrophil infiltration might be the common pathogenesis of IBD and BC. Molecular mechanisms for the treatment of IBD and CC still require further investigation.
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Affiliation(s)
- Jianyong Liu
- Department of Urology, Institute of the Geriatric Medicine, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
- Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China
- Beijing Hospital Continence Center, Beijing, People's Republic of China
| | - Pengjie Wu
- Department of Urology, Institute of the Geriatric Medicine, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
- Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China
- Beijing Hospital Continence Center, Beijing, People's Republic of China
| | - Shicong Lai
- Department of Urology, Peking University People's Hospital, Beijing, 100044, People's Republic of China
| | - Jianye Wang
- Department of Urology, Institute of the Geriatric Medicine, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
- Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
- Beijing Hospital Continence Center, Beijing, People's Republic of China.
- , No. 1 DaHua Road, Dong Dan, Beijing, 100730, China.
| | - Jianlong Wang
- Department of Urology, Institute of the Geriatric Medicine, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
- Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
- Beijing Hospital Continence Center, Beijing, People's Republic of China.
- , No. 1 DaHua Road, Dong Dan, Beijing, 100730, China.
| | - Yaoguang Zhang
- Department of Urology, Institute of the Geriatric Medicine, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
- Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
- Beijing Hospital Continence Center, Beijing, People's Republic of China.
- , No. 1 DaHua Road, Dong Dan, Beijing, 100730, China.
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21
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Kottavadakkeel N, Farzina R, Rajaram A, Mannath S, Sunil A. A Case Report of Follicular Lymphoma in a Crohn's Disease Patient Treated With Azathioprine. Cureus 2023; 15:e50839. [PMID: 38125685 PMCID: PMC10732096 DOI: 10.7759/cureus.50839] [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] [Accepted: 12/20/2023] [Indexed: 12/23/2023] Open
Abstract
Inflammatory bowel disease (IBD) is an autoimmune disorder marked by chronic inflammation affecting the intestines. Crohn's disease (CD) and ulcerative colitis (UC) fall under the IBD umbrella, necessitating diverse treatments, including steroids, immunomodulators like 6-mercaptopurine (6-MP) and azathioprine (AZA), and biological agents. The prolonged use of immunomodulators, such as AZA, is associated with an elevated risk of developing lymphomas. This case report centers on a 77-year-old gentleman regularly monitored by Gastroenterology, undergoing long-term AZA therapy for CD management. He presented with palate swelling and acute-on-chronic back pain, diagnosed with follicular lymphoma in the palate with metastasis. Palliative radiotherapy was administered for the paraspinal lesion, and the patient is currently stable. In conclusion, this case underscores the importance of recognizing the heightened risk of neoplasms, especially lymphomas, in patients undergoing prolonged immunomodulator therapy. It emphasizes the need for a vigilant and comprehensive approach to patient care, transcending conventional paradigms.
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Affiliation(s)
- Nadeer Kottavadakkeel
- Gastroenterology, Pilgrim Hospital Boston, United Lincolnshire Hospital National Health Services (NHS) Trust, Lincolnshire, GBR
| | - Reefat Farzina
- Gastroenterology, Pilgrim Hospital Boston, United Lincolnshire Hospital National Health Services (NHS) Trust, Lincolnshire, GBR
| | - Arun Rajaram
- Gastroenterology and Hepatology, Aster Medcity, Kochi, IND
- Otolaryngology, Pilgrim Hospital Boston, United Lincolnshire Hospital National Health Services (NHS) Trust, Lincolnshire, GBR
| | - Sathia Mannath
- Diabetes and Endocrinology, Pilgrim Hospital Boston, United Lincolnshire Hospital National Health Services (NHS) Trust, Lincolnshire, GBR
| | - Abida Sunil
- Gastroenterology, Pilgrim Hospital Boston, United Lincolnshire Hospital National Health Services (NHS) Trust, Lincolnshire, GBR
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22
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Wang L, Deng JY, Li KP, Shan-Yin, Zhu PY. Inflammatory bowel disease and bladder cancer risk: based on a Mendelian randomization study. BMC Urol 2023; 23:195. [PMID: 38012665 PMCID: PMC10683281 DOI: 10.1186/s12894-023-01346-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Accepted: 10/20/2023] [Indexed: 11/29/2023] Open
Abstract
BACKGROUND Prior epidemiological observational studies have duly documented a correlative link between inflammatory bowel disease (IBD) and bladder cancer (BC); however, the establishment of a definitive causal relationship has remained elusive. The principal objective of this meticulous investigation was to rigorously evaluate the causal nexus between IBD and BC, employing the robust methodology of Mendelian randomization (MR) analysis. METHODS We meticulously performed both univariate and multivariate Mendelian randomization (MVMR) analyses employing publicly accessible genome-wide association study (GWAS) data. The central approach employed for our investigations was inverse variance weighting (IVW) method, while diligently scrutinizing potential sources of heterogeneity and horizontal pleiotropy via the rigorous utilization of Cochran's Q test, the MR-PRESSO method, and MR-Egger. RESULTS In the univariate MR analysis, no causal link was observed between genetic prediction of IBD and BC. Furthermore, both Crohn's disease (CD) and ulcerative colitis (UC) showed no causal association with BC. The consistent association between CD and UC in the MVMR analysis supports this finding. CONCLUSION This study found no genetic basis for the causative association of IBD and BC. It is crucial to emphasize that further comprehensive investigations are warranted to delve into the intricate underlying mechanisms that may contribute to these associations.
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Affiliation(s)
- Li Wang
- Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Jing-Ya Deng
- Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Kun-Peng Li
- Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, China
| | - Shan-Yin
- Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Ping-Yu Zhu
- Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
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23
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Li CJ, Wang YK, Zhang SM, Ren MD, He SX. Global burden of inflammatory bowel disease 1990-2019: A systematic examination of the disease burden and twenty-year forecast. World J Gastroenterol 2023; 29:5751-5767. [PMID: 38075848 PMCID: PMC10701338 DOI: 10.3748/wjg.v29.i42.5751] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 10/13/2023] [Accepted: 10/30/2023] [Indexed: 11/13/2023] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is an idiopathic intestinal disease with various levels and trends in different countries and regions. Understanding the current burden and trends of IBD in various geographical locations is essential to establish effective strategies for prevention and treatment. We report the average annual percentage change (AAPC) and estimated annual percentage change (EAPC) in age-standardized rates (ASR) of IBD in different regions based on the Global Burden of Disease (GBD) study from 1990-2019, and the relationships between IBD and the human development index (HDI) and socio-demographic index (SDI). The prevalence trends of IBD were predicted by gender from 2019-2039. AIM To comprehensively investigate IBD data, providing further insights into the management of this chronic disease. METHODS We collected the information on the incidence of IBD from the GBD study from 1990-2019 to calculate the AAPC and EAPC in ASR of IBD in different regions. The relationships between IBD, HDI, and SDI were analyzed. The Nordpred and Bayesian age-period-cohort models were used to predict the prevalence trends of IBD by gender from 2019-2039, and the reliability of the results was validated. Statistics of all the data in this study were performed using R software (version 4.2.1). RESULTS North America consistently had the highest IBD ASR, while Oceania consistently had the lowest. East Asia had the fastest average annual growth in ASR (2.54%), whereas Central Europe had the fastest decline (1.38%). Countries with a low age-standardized incidence rates in 1990 showed faster growth in IBD while there was no significant correlation in 2019. Additionally, IBD increased faster in countries with a low age-standardized death rates in 1990, whereas the opposite was true in 2019. Analysis of SDI and IBD ASR showed that countries with a high SDI generally had a higher IBD ASR. Finally, the projections showed a declining trend in the incidence of IBD from 2019-2039, but a gradual increase in the number of cases. CONCLUSION As the global population increases and ages, early monitoring and prevention of IBD is important to reduce the disease burden, especially in countries with a high incidence of IBD.
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Affiliation(s)
- Cheng-Jun Li
- Department of Gastroenterology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Yi-Kai Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Shun-Ming Zhang
- School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an 710061, Shaanxi Province, China
| | - Mu-Dan Ren
- Department of Gastroenterology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Shui-Xiang He
- Department of Gastroenterology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
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24
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Li CJ, Wang YK, Zhang SM, Ren MD, He SX. Global burden of inflammatory bowel disease 1990-2019: A systematic examination of the disease burden and twenty-year forecast. World J Gastroenterol 2023; 29:5764-5780. [DOI: 10.3748/wjg.v29.i42.5764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 10/13/2023] [Accepted: 10/30/2023] [Indexed: 11/13/2023] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is an idiopathic intestinal disease with various levels and trends in different countries and regions. Understanding the current burden and trends of IBD in various geographical locations is essential to establish effective strategies for prevention and treatment. We report the average annual percentage change (AAPC) and estimated annual percentage change (EAPC) in age-standardized rates (ASR) of IBD in different regions based on the Global Burden of Disease (GBD) study from 1990-2019, and the relationships between IBD and the human development index (HDI) and socio-demographic index (SDI). The prevalence trends of IBD were predicted by gender from 2019-2039.
AIM To comprehensively investigate IBD data, providing further insights into the management of this chronic disease.
METHODS We collected the information on the incidence of IBD from the GBD study from 1990-2019 to calculate the AAPC and EAPC in ASR of IBD in different regions. The relationships between IBD, HDI, and SDI were analyzed. The Nordpred and Bayesian age-period-cohort models were used to predict the prevalence trends of IBD by gender from 2019-2039, and the reliability of the results was validated. Statistics of all the data in this study were performed using R software (version 4.2.1).
RESULTS North America consistently had the highest IBD ASR, while Oceania consistently had the lowest. East Asia had the fastest average annual growth in ASR (2.54%), whereas Central Europe had the fastest decline (1.38%). Countries with a low age-standardized incidence rates in 1990 showed faster growth in IBD while there was no significant correlation in 2019. Additionally, IBD increased faster in countries with a low age-standardized death rates in 1990, whereas the opposite was true in 2019. Analysis of SDI and IBD ASR showed that countries with a high SDI generally had a higher IBD ASR. Finally, the projections showed a declining trend in the incidence of IBD from 2019-2039, but a gradual increase in the number of cases.
CONCLUSION As the global population increases and ages, early monitoring and prevention of IBD is important to reduce the disease burden, especially in countries with a high incidence of IBD.
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Affiliation(s)
- Cheng-Jun Li
- Department of Gastroenterology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Yi-Kai Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
| | - Shun-Ming Zhang
- School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an 710061, Shaanxi Province, China
| | - Mu-Dan Ren
- Department of Gastroenterology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Shui-Xiang He
- Department of Gastroenterology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
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25
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Axiaris G, Ioannou A, Papoutsaki M, Marinos L, Liontos M, Michopoulos S, Zampeli E. Case Report: Malignant melanoma in a patient with Crohn's disease treated with ustekinumab. F1000Res 2023; 11:424. [PMID: 37867623 PMCID: PMC10589619 DOI: 10.12688/f1000research.110356.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/02/2023] [Indexed: 10/24/2023] Open
Abstract
The cornerstone of inflammatory bowel disease (IBD) treatment is immunomodulators. IBD patients are at increased risk of intestinal and extraintestinal malignancy. Ustekinumab is a fully humanized monoclonal anti-IL12/23 antibody with a good safety profile. Malignancies of breast, colon, head and neck, kidney, prostate, thyroid, and non-melanoma skin cancer have been reported among patients who received ustekinumab. We report the case of a 42-year-old Crohn's patient on long-term treatment with ustekinumab, who developed achromatic malignant melanoma. Crohn's was diagnosed at the age of 15, with upper and lower gastrointestinal involvement and was initially treated with azathioprine (2mg/kg for 4 years) and infliximab (5mg/kg for 6 weeks). Due to ileal obstruction, the patient underwent stricturoplasty and received adalimumab (40mg every other week) for two years. He then discontinued therapy and a year later underwent right hemicolectomy. Adalimumab was reinstituted (40mg every other week) and the patient remained in clinical remission for two years. His overall exposure to adalimumab was four years. Ustekinumab was initiated due to a relapse and after 3 years, an incident of scalp itching led to the diagnosis metastatic achromatic malignant melanoma bearing BRAF V600E mutation. He received targeted therapy with an initial good response. We aim to point out the risk of dermatologic malignancy in IBD patients on long-term immunosuppression and the lifelong and meticulous evaluation that is required.
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Affiliation(s)
- Georgios Axiaris
- Gastroenterology Department, Alexandra General Hospital, Athens, Greece, 11528, Greece
| | - Alexandros Ioannou
- Gastroenterology Department, Alexandra General Hospital, Athens, Greece, 11528, Greece
| | - Marina Papoutsaki
- Dermatology Department, Syggros Hospital, Athens, Greece, 11528, Greece
| | - Leonidas Marinos
- Pathology Department, Evangelismos Hospital, Atherns, Greece, 11528, Greece
| | - Michael Liontos
- Oncology Department, Alexandra General Hospital, Athens, Greece, 11528, Greece
| | - Spyridon Michopoulos
- Gastroenterology Department, Alexandra General Hospital, Athens, Greece, 11528, Greece
| | - Evanthia Zampeli
- Gastroenterology Department, Alexandra General Hospital, Athens, Greece, 11528, Greece
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26
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Murthy SK, Kuenzig ME, Windsor JW, Matthews P, Tandon P, Benchimol EI, Bernstein CN, Bitton A, Coward S, Jones JL, Kaplan GG, Lee K, Targownik LE, Peña-Sánchez JN, Rohatinsky N, Ghandeharian S, Meka S, Chis RS, Gupta S, Cheah E, Davis T, Weinstein J, Im JHB, Goddard Q, Gorospe J, Loschiavo J, McQuaid K, D’Addario J, Silver K, Oppenheim R, Singh H. The 2023 Impact of Inflammatory Bowel Disease in Canada: Cancer and IBD. J Can Assoc Gastroenterol 2023; 6:S83-S96. [PMID: 37674502 PMCID: PMC10478814 DOI: 10.1093/jcag/gwad006] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/08/2023] Open
Abstract
Cancer is a major cause of morbidity and mortality among people with inflammatory bowel disease (IBD). Intestinal cancers may arise as a complication of IBD itself, while extra-intestinal cancers may arise due to some of the immunosuppressive therapies used to treat IBD. Colorectal cancer (CRC) and small bowel cancer risks remain elevated among persons with IBD as compared to age-and sex-matched members of the general population, and the lifetime risk of these cancers is strongly correlated to cumulative intestinal inflammatory burden. However, the cumulative risk of cancer, even among those with IBD is still low. Some studies suggest that IBD-CRC incidence has declined over the years, possibly owing to improved treatment standards and improved detection and management of early neoplastic lesions. Across studies of extra-intestinal cancers, there are generally higher incidences of melanoma, hepatobiliary cancer, and lung cancer and no higher incidences of breast cancer or prostate cancer, with equivocal risk of cervical cancer, among persons with IBD. While the relative risks of some extra-intestinal cancers are increased with treatment, the absolute risks of these cancers remain low and the decision to forego treatment in light of these risks should be carefully weighed against the increased risks of intestinal cancers and other disease-related complications with undertreated inflammatory disease. Quality improvement efforts should focus on optimized surveillance of cancers for which surveillance strategies exist (colorectal cancer, hepatobiliary cancer, cervical cancers, and skin cancers) and the development of cost-effective surveillance strategies for less common cancers associated with IBD.
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Affiliation(s)
- Sanjay K Murthy
- Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- The Ottawa Hospital IBD Centre, Ottawa, Ontario, Canada
| | - M Ellen Kuenzig
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Joseph W Windsor
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | | | - Parul Tandon
- Department of Gastroenterology and Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Eric I Benchimol
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
- ICES, Toronto, Ontario, Canada
- Department of Paediatrics, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Institute of Health Policy, Management, and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Charles N Bernstein
- Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Alain Bitton
- Division of Gastroenterology and Hepatology, McGill University Health Centre IBD Centre, McGill University, Montréal, Quebec, Canada
| | - Stephanie Coward
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Jennifer L Jones
- Departments of Medicine, Clinical Health, and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Gilaad G Kaplan
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Kate Lee
- Crohn’s and Colitis Canada, Toronto, Ontario, Canada
| | - Laura E Targownik
- Division of Gastroenterology and Hepatology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Juan-Nicolás Peña-Sánchez
- Department of Community Health and Epidemiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Noelle Rohatinsky
- College of Nursing, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | | | - Saketh Meka
- Department of Neuroscience, McGill University, Montreal, Quebec, Canada
| | - Roxana S Chis
- Department of Gastroenterology and Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Sarang Gupta
- Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Eric Cheah
- Department of Gastroenterology and Clinical Nutrition, The Royal Children’s Hospital Melbourne, Parkville, Australia
| | - Tal Davis
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Jake Weinstein
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - James H B Im
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada
- Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Quinn Goddard
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Julia Gorospe
- Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | | | | | | | - Ken Silver
- Crohn’s and Colitis Canada, Toronto, Ontario, Canada
| | | | - Harminder Singh
- Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada
- Department of Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- CancerCare Manitoba Research Institute, Winnipeg, Manitoba, Canada
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Min Y, Liu Z, Li R, Jin J, Wei Z, Pei Y, Hu X, Peng X. Association between inflammatory bowel disease and pancreatic cancer: results from the two-sample Mendelian randomization study. Front Oncol 2023; 13:1155123. [PMID: 37692850 PMCID: PMC10492092 DOI: 10.3389/fonc.2023.1155123] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 08/14/2023] [Indexed: 09/12/2023] Open
Abstract
Background The nuanced relationship between inflammatory bowel disease (IBD) and pancreatic cancer is noticed in recent years. However, the underlying causal effects of these two diseases are still unclear. Methods The two-sample mendelian randomization (MR) was conducted to explore the causal effect of IBD condition on pancreatic cancer. Methods of Wald ratio, inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode were used to investigate the causal relationship between IBD and pancreatic cancer. Besides, Cochrane's Q test, MR-Egger, and leave-one-out method were further conducted to detect heterogeneity, stability, and pleiotropy of MR results. Results In the MR analysis, we found Crohn's disease had a significant causal effect on pancreatic cancer. Specifically, Crohn's disease would increase 11.1% the risk of pancreatic cancer by the IVW method (p= 0.022), 33.8% by MR Egger (p= 0.015), by 35.3% by the Weighted model (p= 0.005). Regarding ulcerative colitis, there was no statistically significant causal effect observed on pancreatic cancer (p>0.05). Additionally, the pleiotropic test and Leave-one-out analysis both proved the validity and reliability of the present two-sample MR analyses. Conclusion This study indicates that IBD, particularly Crohn's disease, is causality associated with increased risk of pancreatic cancer. Our results may help public health managers to make better follow-up surveillance of IBD patients.
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Affiliation(s)
- Yu Min
- Department of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University, Cheng Du, Sichuan, China
| | - Zheran Liu
- Department of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University, Cheng Du, Sichuan, China
| | - Ruidan Li
- Department of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University, Cheng Du, Sichuan, China
| | - Jing Jin
- Department of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University, Cheng Du, Sichuan, China
| | - Zhigong Wei
- Department of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University, Cheng Du, Sichuan, China
| | - Yiyan Pei
- Department of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University, Cheng Du, Sichuan, China
| | - Xiaolin Hu
- West China School of Nursing, West China Hospital, Sichuan University, Cheng Du, Sichuan, China
| | - Xingchen Peng
- Department of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University, Cheng Du, Sichuan, China
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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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Kim J, Jung JH, Jo H, Kim MH, Kang DR, Kim HM. Risk of uterine cervical cancer in inflammatory bowel disease: a systematic review and meta-analysis. Scand J Gastroenterol 2023; 58:1412-1421. [PMID: 37517000 DOI: 10.1080/00365521.2023.2238101] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Revised: 06/25/2023] [Accepted: 07/13/2023] [Indexed: 08/01/2023]
Abstract
BACKGROUND AND AIMS There are limited data on the association between uterine cervical cancer (UCC) and inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC). METHODS This systematic review and meta-analysis assessed the risk of UCC in patients with IBD. We searched MEDLINE, Embase, Cochrane Library, Scopus, Web of Science, ClinicalTrials.gov, gray literature and conference proceedings for studies published before 21 January 2022. Two reviewers independently screened studies, extracted data and assessed quality using the Newcastle-Ottawa Scale. Subgroup analyses were based on IBD type, biologic era, immunosuppression status, study location and design, and publication status. Fifteen studies were included. RESULTS The pooled relative risk (RR) of UCC in IBD was 1.34 (95% confidence interval [CI], 1.07-1.69; I2 = 53.4%). In subgroup analyses, the pooled RRs of UCC in CD and UC were 1.18 (95% CI, 0.97-1.42) and 1.50 (95% CI, 1.01-12.21), respectively. The pooled RRs of UCC in pre-biologic and biologic eras were 1.36 (95% CI, 0.83-2.23) and 1.99 (95% CI, 1.03-3.86), respectively. The pooled RR of UCC in immunomodulator users was 2.18 (95% CI, 0.81-5.87). The pooled RRs of UCC in Asia, Europe and North America were 5.65 (95% CI, 2.65-12.07), 1.13 (95% CI, 0.96-1.34) and 1.38 (95% CI, 1.10-1.73), respectively. CONCLUSIONS The risk of UCC was significantly increased in IBD, particularly in UC but not in CD, suggesting that women with IBD should undergo regular UCC screening and consider vaccination.
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Affiliation(s)
- Jihoon Kim
- Department of Medicine, Yonsei University Wonju College of Medicine, Wonju, South Korea
| | - Jae Hung Jung
- Department of Urology, Yonsei University Wonju College of Medicine, Wonju, South Korea
- Center of Evidence Based Medicine, Institute of Convergence Science, Yonsei University, Seoul, South Korea
| | - Halim Jo
- Department of Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea
| | - Myung Ha Kim
- Yonsei Wonju Medical Library, Yonsei University Wonju College of Medicine, Wonju, South Korea
| | - Dae Ryong Kang
- Center of Biomedical Data Science, Yonsei University Wonju College of Medicine, Wonju, South Korea
| | - Hee Man Kim
- Cancer Prevention Center, Severance Cancer Hospital, Yonsei University College of Medicine, Seoul, South Korea
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30
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Balda A, Wani I, Roohi TF, Krishna KL, Mehdi S, Nadiga AP, Makkapati M, Baig MAI. Psoriasis and skin cancer - Is there a link? Int Immunopharmacol 2023; 121:110464. [PMID: 37390565 DOI: 10.1016/j.intimp.2023.110464] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Revised: 05/18/2023] [Accepted: 06/05/2023] [Indexed: 07/02/2023]
Abstract
A chronic auto-immune-mediated disease Psoriasis is associated with manycoexisting or co-occurringconditions, which include a significant risk of malignancies, especiallyskin tumours. Numerous studies were done to understand whether psoriasis itself, comorbidities related to psoriasis, or psoriasis treatment might increase the risk of neoplasms. We reviewed the relation between psoriasis and cancer risk, also the significance of inflammation in cancer The various classes of drugs used to treat psoriasis, including biologics like tumour necrosis factor (TNF) inhibitors; and how they increase cancer risk are deliberated. Literature was collated for the past five years from the data bases like PubMed, Medline, Google Scholar, etc. Literatures discussing the skin cancer linked to psoriasis were reviewed. Possible mechanisms associated between inflammation and psoriasis; skin cancer was explained in the context of the several psoriasis medications that increase the likelihood of skin cancer. The risk of cancer in other cutaneous auto-inflammatory diseases is also elucidated. It is frequently observed that increased doses of PUVA therapy, immunosuppressive medications, and lifestyle changes alter the aetiology of the tumours. This review is conceptualized to shed the light on probable mechanisms involved in these connections as well as the chance of cancer in psoriasis patients.
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Affiliation(s)
- Aayushi Balda
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysore 570015, Karnataka, India
| | - Irshad Wani
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysore 570015, Karnataka, India
| | - Tamsheel Fatima Roohi
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysore 570015, Karnataka, India
| | - K L Krishna
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysore 570015, Karnataka, India.
| | - Seema Mehdi
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysore 570015, Karnataka, India
| | - Abhishek Pr Nadiga
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysore 570015, Karnataka, India
| | - Manasa Makkapati
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysore 570015, Karnataka, India
| | - Md Awaise Iqbal Baig
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysore 570015, Karnataka, India
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Peixoto RD, Ferreira AR, Cleary JM, Fogacci JP, Vasconcelos JP, Jácome AA. Risk of Cancer in Inflammatory Bowel Disease and Pitfalls in Oncologic Therapy. J Gastrointest Cancer 2023; 54:357-367. [PMID: 35288863 DOI: 10.1007/s12029-022-00816-0] [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] [Accepted: 02/22/2022] [Indexed: 10/18/2022]
Abstract
BACKGROUND Inflammatory bowel disease (IBD), represented by ulcerative colitis and Crohn's disease, is an idiopathic condition caused by a dysregulated immune response to host intestinal microflora, leading to chronic relapsing intestinal inflammation. Individuals with IBD are more prone to die from several diseases, including cancer. METHODS An extensive search was conducted of PubMed using the following medical subject heading-"inflammatory bowel disease" OR "Crohn's disease" OR "ulcerative colitis" AND "cancer." RESULTS In this review article, we discuss the oncogenic mechanisms and genomics of colitis-associated colorectal cancer. Beyond this, we describe the multiple other malignancies that IBD patients are at risk for, discuss caveats in the screening and diagnosis of those cancers, and shed light on pitfalls on the management and treatment of cancer in IBD patients. CONCLUSION Patients, caregivers, and health professionals who deal with IBD must be educated on how to identify warning signs so that cancers can be diagnosed and treated as early as possible.
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Kim J, Jo H, Ha MC, Kim H, Lee JK, Han JH, Lee SH, Kang DR, Kim SY, Kim HS, Kim HM. Elevated risk of cervical cancer in elderly women with incident ulcerative colitis in South Korea. Sci Rep 2023; 13:8323. [PMID: 37221276 DOI: 10.1038/s41598-023-33476-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Accepted: 04/13/2023] [Indexed: 05/25/2023] Open
Abstract
The association between ulcerative colitis (UC) and uterine cervical cancer is still unclear. To investigate cervical cancer risk in South Korean women with UC, we analyzed the Korean National Health Insurance claims data. UC was defined using both ICD-10 codes and UC-specific prescriptions. We analyzed incident cases of UC diagnosed between 2006 and 2015. Age-matched women without UC (control group) were randomly selected from the general population (1:3 ratio). Hazard ratios were calculated using multivariate Cox proportional hazard regression, and the event was defined as occurrence of cervical cancer. A total of 12,632 women with UC and 36,797 women without UC were enrolled. The incidence of cervical cancer was 38.8 per 100,000 women per year in UC patients and 25.7 per 100,000 women per year in controls, respectively. The adjusted HR for cervical cancer was 1.56 (95% CI 0.97-2.50) in the UC group with reference to the control group. When stratified by age, the adjusted HR for cervical cancer was 3.65 (95% CI 1.54-8.66) in elderly UC patients (≥ 60 years) compared to elderly control group (≥ 60 years). Within UC patients, increased age (≥ 40 years) and low socioeconomic status were associated with an increased risk of cervical cancer. The incidence of cervical cancer was found to be higher among elderly patients (≥ 60 years) with newly diagnosed UC in South Korea, compared to age-matched controls. Therefore, regular cervical cancer screening is recommended for elderly patients who have recently been diagnosed with UC.
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Affiliation(s)
- Jihoon Kim
- Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Halim Jo
- Department of Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Min Chul Ha
- Department of Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Hyunil Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Jung Kuk Lee
- Department of Biostatistics, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Jae Hun Han
- Department of Biostatistics, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - San-Hui Lee
- Department of Obstetrics and Gynecology, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Dae Ryong Kang
- Department of Precision Medicine and Biostatistics, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Su Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Hyun-Soo Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
| | - Hee Man Kim
- Health Promotion Center, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
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Conti Bellocchi MC, Crinò SF, De Marchi G, De Pretis N, Ofosu A, Caldart F, Ciccocioppo R, Frulloni L. A Clinical and Pathophysiological Overview of Intestinal and Systemic Diseases Associated with Pancreatic Disorders: Causality or Casualty? Biomedicines 2023; 11:biomedicines11051393. [PMID: 37239064 DOI: 10.3390/biomedicines11051393] [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: 04/05/2023] [Revised: 05/01/2023] [Accepted: 05/05/2023] [Indexed: 05/28/2023] Open
Abstract
The relationship between chronic intestinal disease, including inflammatory bowel disease (IBD) and celiac disease (CelD), and pancreatic disorders has been little investigated. Although an increased risk of acute pancreatitis (AP), exocrine pancreatic insufficiency with or without chronic pancreatitis, and chronic asymptomatic pancreatic hyperenzymemia have been described in these patients, the pathogenetic link remains unclear. It may potentially involve drugs, altered microcirculation, gut permeability/motility with disruption of enteric-mediated hormone secretion, bacterial translocation, and activation of the gut-associated lymphoid tissue related to chronic inflammation. In addition, the risk of pancreatic cancer seems to be increased in both IBD and CelD patients with unknown pathogenesis. Finally, other systemic conditions (e.g., IgG4-related disease, sarcoidosis, vasculitides) might affect pancreatic gland and the intestinal tract with various clinical manifestations. This review includes the current understandings of this enigmatic association, reporting a clinical and pathophysiological overview about this topic.
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Affiliation(s)
| | - Stefano Francesco Crinò
- Diagnostic and Interventional Endoscopy of Pancreas, Pancreas Institute, University of Verona, 37134 Verona, Italy
| | - Giulia De Marchi
- Gastroenterology Unit, Department of Medicine, Pancreas Institute, University of Verona, 37134 Verona, Italy
| | - Nicolò De Pretis
- Gastroenterology Unit, Department of Medicine, Pancreas Institute, University of Verona, 37134 Verona, Italy
| | - Andrew Ofosu
- Division of Gastroenterology and Hepatology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
| | - Federico Caldart
- Gastroenterology Unit, Department of Medicine, Pancreas Institute, University of Verona, 37134 Verona, Italy
| | - Rachele Ciccocioppo
- Gastroenterology Unit, Department of Medicine, Pancreas Institute, University of Verona, 37134 Verona, Italy
| | - Luca Frulloni
- Gastroenterology Unit, Department of Medicine, Pancreas Institute, University of Verona, 37134 Verona, Italy
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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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35
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Kim HM, Kim J, Kim H, Park SC, Lee JK, Kang DR, Kim SY, Kim HS. Risk of Gastric Cancer among Patients with Newly Diagnosed Ulcerative Colitis: A Nationwide Population-Based Study. J Clin Med 2023; 12:jcm12082843. [PMID: 37109180 PMCID: PMC10141013 DOI: 10.3390/jcm12082843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 04/01/2023] [Accepted: 04/11/2023] [Indexed: 04/29/2023] Open
Abstract
BACKGROUND Few studies have investigated the risk of gastric cancer (GC) in ulcerative colitis (UC), and the results have been inconsistent. This study aimed to assess the risk of gastric cancer in newly diagnosed UC patients. METHODS Based on claims data from Korean National Health Insurance from January 2006 to December 2015, we identified 30,546 patients with UC and randomly selected 88,829 non-UC individuals as controls, who were matched by age and sex. Multivariate Cox proportional hazards regression was used to calculate adjusted hazard ratios (HRs) for gastric cancer events, with covariates taken into account. RESULTS During the study period, a total of 77 (0.25%) patients with UC and 383 (0.43%) non-UC individuals were diagnosed with GC. After multivariable adjustment, the HR for GC was 0.60 (95% CI: 0.47-0.77) in patients with UC, using non-UC individuals as the reference group. When stratified by age, the adjusted HRs for GC in UC patients were 0.19 (95% CI: 0.04-0.98) for those aged 20-39 years at the time of UC diagnosis, 0.65 (95% CI: 0.45-0.94) for 40-59, and 0.60 (95% CI: 0.49-0.80) for ≥60 as compared to non-UC individuals in the corresponding age groups. When stratified by sex, the adjusted HR for GC was 0.54 (95% CI: 0.41-0.73) in male UC patients of all ages. Within UC patients, a multivariable analysis revealed that the HR for GC was 12.34 (95% CI: 2.23-68.16) for those aged ≥ 60 years at the time of diagnosis of UC. CONCLUSIONS Patients with UC had a decreased GC risk compared with non-UC individuals in South Korea. Within the UC population, advancing age (≥60 years) was identified as a significant risk factor for GC.
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Affiliation(s)
- Hee Man Kim
- Health Promotion Center, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea
| | - Jihoon Kim
- Department of Physiology, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea
| | - Hyunil Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea
| | - Soon Chang Park
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea
| | - Jung Kuk Lee
- Department of Biostatistics, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea
| | - Dae Ryong Kang
- Department of Precision Medicine & Biostatistics, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea
| | - Su Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea
| | - Hyun-Soo Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea
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Wetwittayakhlang P, Tselekouni P, Al-Jabri R, Bessissow T, Lakatos PL. The Optimal Management of Inflammatory Bowel Disease in Patients with Cancer. J Clin Med 2023; 12:2432. [PMID: 36983432 PMCID: PMC10056442 DOI: 10.3390/jcm12062432] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/11/2023] [Accepted: 03/21/2023] [Indexed: 03/30/2023] Open
Abstract
Patients with inflammatory bowel disease (IBD) have an increased risk of cancer secondary to chronic inflammation and long-term use of immunosuppressive therapy. With the aging IBD population, the prevalence of cancer in IBD patients is increasing. As a result, there is increasing concern about the impact of IBD therapy on cancer risk and survival, as well as the effects of cancer therapies on the disease course of IBD. Managing IBD in patients with current or previous cancer is challenging since clinical guidelines are based mainly on expert consensus. Evidence is rare and mainly available from registries or observational studies. In contrast, excluding patients with previous/or active cancer from clinical trials and short-term follow-up can lead to an underestimation of the cancer or cancer recurrence risk of approved medications. The present narrative review aims to summarize the current evidence and provide practical guidance on the management of IBD patients with cancer.
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Affiliation(s)
- Panu Wetwittayakhlang
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai 90110, Songkhla, Thailand
| | - Paraskevi Tselekouni
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada
| | - Reem Al-Jabri
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada
| | - Talat Bessissow
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada
| | - Peter L. Lakatos
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada
- Department of Internal Medicine and Oncology, Semmelweis University, 1085 Budapest, Hungary
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Wu S, Xie S, Yuan C, Yang Z, Liu S, Zhang Q, Sun F, Wu J, Zhan S, Zhu S, Zhang S. Inflammatory Bowel Disease and Long-term Risk of Cancer: A Prospective Cohort Study Among Half a Million Adults in UK Biobank. Inflamm Bowel Dis 2023; 29:384-395. [PMID: 35639937 DOI: 10.1093/ibd/izac096] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND This study aims to examine the prospective association of inflammatory bowel disease (IBD) with long-term risk of overall, site-specific cancer and cancer-specific mortality in middle-aged and older people. METHODS The study included participants free of any cancer at baseline from the UK Biobank, with IBD patients as an exposure group and non-IBD patients as a reference group. Primary outcome was the incidence of overall cancer and cancer-specific mortality. Secondary outcomes included site-specific cancers and types of digestive cancers. Cox proportional hazard model was used to investigate the associated risk of incident malignancies and related mortality. RESULTS Among 455 927 participants, 5142 were diagnosed with IBD (3258 ulcerative colitis [UC]; 1449 Crohn's disease [CD]; others unspecified). During a median of 12.2-year follow-up, 890 cases of incident cancer were identified in IBD patients (15.74 per 1000 person years) compared with 63 675 cases in reference individuals (12.46 per 1000 person years). Of these cases, 220 and 12 838 cancer-specific deaths occurred in IBD and non-IBD groups. Compared with non-IBD participants, the adjusted hazard ratio (AHR) for overall cancer and cancer-specific mortality was 1.17 (95% CI, 1.09-1.25) and 1.26 (95% CI, 1.18-1.35) among IBD patients, with an AHR of 1.15 (95% CI, 1.02-1.31) and 1.38 (95% CI, 1.08-1.75) in UC and 1.15 (95% CI, 1.06-1.25) and 1.25 (95% CI, 1.06-1.49) in CD, respectively. Specifically, increased risk of digestive (1.33; 95% CI, 1.12-1.57), nonmelanoma (1.25; 95% CI, 1.11-1.41), and male genital (1.29; 95% CI, 1.09-1.52) cancers was observed in IBD patients. CONCLUSIONS Compared with non-IBD, IBD may be associated with an increased risk of overall cancer and cancer-specific mortality, particularly digestive cancers, nonmelanoma and male genital cancers.
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Affiliation(s)
- Shanshan Wu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, China
| | - Sian Xie
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, China
| | - Changzheng Yuan
- School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, China
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
| | - Zhirong Yang
- Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China
- Primary Care Unit, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, CB18RN, UK
| | - Si Liu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, China
| | - Qian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, China
| | - Feng Sun
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, 100191, China
| | - Jing Wu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, China
| | - Siyan Zhan
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, 100191, China
| | - Shengtao Zhu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, China
| | - Shutian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, China
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Egberg MD, Zhang X, Smitherman AB, Kappelman MD. Low Risk of Lymphoma in Pediatric Patients Treated for Inflammatory Bowel Disease. Am J Gastroenterol 2023; 118:354-359. [PMID: 36219181 PMCID: PMC9898086 DOI: 10.14309/ajg.0000000000002053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Accepted: 10/06/2022] [Indexed: 11/07/2022]
Abstract
INTRODUCTION Despite the effectiveness of immune-suppressing therapies in treating pediatric inflammatory bowel diseases (IBDs), concerns of lymphoma may limit their use. We used a large administrative claims database to evaluate the risk of lymphoma in pediatric IBD and conducted a case series analysis of medication exposure in children diagnosed with lymphoma. METHODS We analyzed administrative claims from the 2007 to 2018 IQVIA database and identified pediatric (≤18 years) patients with Crohn's disease or ulcerative colitis using International Classification of Diseases, 9th or 10th Revision codes and pharmacy claims. Lymphoma cases were identified by diagnosis codes and confirmed by independent claim-by-claim review by a pediatric oncologist and gastroenterologist. We calculated incidence rates for lymphoma among patients with and without pharmacy claims for treatment followed by treatment description among those who developed lymphoma during follow-up. RESULTS A total of 10,777 pediatric patients with IBD received ≥1 IBD therapy (median age 15 years [12-17], 45% female and 61% diagnosed with Crohn's disease) during 28,292 patient-years of follow-up. Among treated patients, 5 lymphoma cases were identified (incidence rate 17.7/100,000 patient-years; 95% confidence interval 6.5-39.2). Of these, 4 were treated with a thiopurine before lymphoma diagnosis, and none received anti-tumor necrosis factor-α (anti-TNF) monotherapy. DISCUSSION The overall lymphoma incidence was low among our cohort of treated pediatric patients with IBD. We observed no cases of lymphoma among patients prescribed anti-TNF monotherapy. These findings reinforce the relative safety of anti-TNF monotherapy for the treatment of pediatric IBD.
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Affiliation(s)
- Matthew D. Egberg
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC
- Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Xian Zhang
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Andrew B. Smitherman
- Department of Pediatrics, Division of Hematology and Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Michael D. Kappelman
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC
- Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC
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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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40
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Alehashemi S, Ward MM. Risk of Hematologic Malignancies in Elderly Patients With Ankylosing Spondylitis: A Cohort Study and Systematic Review. Mayo Clin Proc 2023; 98:100-110. [PMID: 36470752 PMCID: PMC9822846 DOI: 10.1016/j.mayocp.2022.06.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 05/09/2022] [Accepted: 06/30/2022] [Indexed: 12/04/2022]
Abstract
OBJECTIVE To examine the risk of hematologic malignancies in older adults with ankylosing spondylitis (AS). PATIENTS AND METHODS We used US Medicare data from January 1, 1999, to December 31, 2010, to identify a population-based cohort of beneficiaries with AS. We also included beneficiaries with inflammatory bowel disease (IBD) as disease controls and beneficiaries without AS or IBD as unaffected controls. We excluded those treated with tumor necrosis factor inhibitors in this period. We followed up each group for new diagnosis claims for hematologic malignancies until September 30, 2015. RESULTS We included 12,451 beneficiaries with AS, 234,905 with IBD, and 10,975,340 unaffected controls, with a mean follow-up of 9.9, 9.3, and 8.0 years, respectively. We identified 297 hematologic malignancies in the AS group, 4538 malignancies in the IBD group, and 128,239 malignancies in unaffected controls. The standardized incidence ratio in AS vs unaffected controls was 1.39 (95% CI, 1.05 to 1.61) for non-Hodgkin lymphoma, 1.50 (95% CI, 1.17 to 1.92) for chronic lymphocytic leukemia, and 1.52 (95% CI, 1.12 to 2.06) for multiple myeloma. Risks of acute myeloid leukemia and chronic myeloid leukemia were not elevated in AS, and there were too few cases of Hodgkin lymphoma to compute risks. Risks were comparable to those of beneficiaries with IBD. We also performed a systematic literature review of the risk of hematologic malignancy in AS, focusing on age associations, which have not been previously examined. We identified 21 studies in the systematic literature review, which included mainly young or middle-aged patients. Results suggested that AS was largely not associated with an increased risk of hematologic malignancies. Two cohort studies reported an increased risk of multiple myeloma in AS. CONCLUSION The risks of non-Hodgkin lymphoma, chronic lymphocytic leukemia, and multiple myeloma are increased among elderly patients with AS.
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MESH Headings
- Middle Aged
- Humans
- Aged
- United States/epidemiology
- Multiple Myeloma/complications
- Cohort Studies
- Leukemia, Lymphocytic, Chronic, B-Cell/epidemiology
- Leukemia, Lymphocytic, Chronic, B-Cell/complications
- Spondylitis, Ankylosing/complications
- Spondylitis, Ankylosing/drug therapy
- Spondylitis, Ankylosing/epidemiology
- Medicare
- Hematologic Neoplasms/complications
- Lymphoma, Non-Hodgkin/epidemiology
- Lymphoma, Non-Hodgkin/etiology
- Lymphoma, Non-Hodgkin/pathology
- Inflammatory Bowel Diseases/complications
- Inflammatory Bowel Diseases/drug therapy
- Inflammatory Bowel Diseases/epidemiology
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Affiliation(s)
- Sara Alehashemi
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
| | - Michael M Ward
- Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD
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Qu-Yu-Jie-Du Decoction Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulation of Neutrophils and Macrophage Infiltration. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:3762591. [DOI: 10.1155/2022/3762591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 11/05/2022] [Accepted: 11/11/2022] [Indexed: 12/12/2022]
Abstract
Background. Inflammatory bowel disease (IBD) is becoming a global disease. A percentage of IBD patients will not react to therapy or will lose their response. Qu-Yu-Jie-Du Decoction (QYJD) is a traditional Chinese medicine formula commonly used for intestinal diseases. It has been reported that QYJD has an anti-inflammatory effect, but the mechanism is not fully understood. In this study, we mainly evaluated the anti-inflammatory effect of QYJD and explored the possible mechanisms. Methods. Twenty-four BALB/c mice were randomly divided into 4 groups according to their body weight, namely, the control group, the dextran sulfate sodium (DSS) group, the DSS + QYJD group, and the QYJD group. Mice were given 3% DSS drinking water freely, and at the same time, mice were given normal saline or QYJD (4.44 mg/g/d), respectively. Mental state, faeces, and weight were recorded every day. On the 10th day, the mice were sacrificed and collected for investigation. The length of the mice colon was measured. Histological analysis was used to detect the morphological changes in the colon. Immunohistochemistry was used to measure the infiltration of macrophages (F4/80, CD163) and neutrophils (Ly6G). Colorimetry was used to detect the myeloperoxidase (MPO) activity of colon tissues. ELISA was utilized to detect associated inflammatory cytokines and chemokines in colon tissues. Results. QYJD alleviated the weight loss and colitis symptoms of mice caused by DSS. QYJD fought against the shortening of the intestine caused by DSS; that is, it improved the decline of intestinal compliance in mice and had a protective effect on colon tissues. The mechanisms were related to downregulating macrophages and neutrophils in colon tissues of infiltration. Besides, QYJD simultaneously reduced the activity of myeloperoxidase activity (MPO) and the contents of IL-1β, IL-6, TNF-α, TGF-β, CCL2, and CXCL2 in colon tissues. Conclusions. QYJD can ameliorate DSS-induced colitis in mice and the mechanism is connected with a reduction in neutrophil and macrophage infiltration.
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Na JE, Kim TJ, Lee YC, Kim JE, Kim ER, Hong SN, Chang DK, Kim YH. Risk of prostate cancer in patients with inflammatory bowel disease: a nationwide cohort study in South Korea. Therap Adv Gastroenterol 2022; 15:17562848221137430. [PMID: 36458049 PMCID: PMC9706079 DOI: 10.1177/17562848221137430] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 10/04/2022] [Indexed: 11/22/2022] Open
Abstract
Background Several studies have suggested an association between inflammatory bowel disease (IBD) and the risk of prostate cancer development. However, these findings are inconsistent, and studies based on Asian populations are limited. Objectives We compared the risk of prostate cancer according to IBD status using the Korean National Health Insurance Service database. Design A population-based retrospective cohort of age-matched 59,044 non-IBD patients and 14,761 IBD patients between January 2009 and December 2011 was analyzed up to December 2017. Methods The risk of prostate cancer was compared between patients with IBD and controls using the Cox proportional hazards regression model and Kaplan-Meier survival analysis. Results During a median follow-up of 6 years, the incidence rate of prostate cancer was 264 per 100,000 person-years in non-IBD patients and 242 per 100,000 person-years in patients with IBD. IBD status was not associated with the risk of prostate cancer compared to non-IBD [adjusted hazard ratio (aHR) 0.93, 95% confidence interval (CI): 0.80-1.08, p = 0.32). The cumulative incidence of prostate cancer did not differ by IBD status (non-IBD patients versus IBD patients: log-rank p = 0.27; non-IBD patients versus ulcerative colitis versus Crohn's disease: log-rank p = 0.42). In multivariate analysis, age was an independent risk factor for the development of prostate cancer (HR 1.03, 95% CI: 1.02-1.03, p < 0.001). Conclusion In our population-based study, IBD status was not associated with the risk of prostate cancer.
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Affiliation(s)
- Ji Eun Na
- Department of Medicine, Inje University
Haeundae Paik Hospital, Busan, Republic of Korea
| | - Tae Jun Kim
- Division of Gastroenterology, Department of
Medicine, Samsung Medical Center, Sungkyunkwan University School of
Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea
| | - Yeong Chan Lee
- Department of Digital Health, Samsung Advanced
Institute for Health Sciences & Technology, Sungkyunkwan University,
Seoul, Republic of Korea
| | - Ji Eun Kim
- Department of Medicine, Samsung Medical Center,
Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Eun Ran Kim
- Department of Medicine, Samsung Medical Center,
Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sung Noh Hong
- Department of Medicine, Samsung Medical Center,
Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Kyung Chang
- Department of Medicine, Samsung Medical Center,
Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Young-Ho Kim
- Division of Gastroenterology, Department of
Medicine, Samsung Medical Center, Sungkyunkwan University School of
Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea
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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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Piovani D, Hassan C, Repici A, Rimassa L, Carlo-Stella C, Nikolopoulos GK, Riboli E, Bonovas S. Risk of Cancer in Inflammatory Bowel Diseases: Umbrella Review and Reanalysis of Meta-analyses. Gastroenterology 2022; 163:671-684. [PMID: 35643170 DOI: 10.1053/j.gastro.2022.05.038] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 05/16/2022] [Accepted: 05/18/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS To summarize the epidemiologic evidence and assess the validity of claimed associations of inflammatory bowel diseases (IBDs) with overall and site-specific cancer risk. METHODS We systematically searched PubMed, Embase, and Scopus from inception to May 10, 2021, to identify and comprehensively reanalyze the data of meta-analyses on associations between IBDs (ie, Crohn's disease [CD] and ulcerative colitis [UC]) and subsequent risk of cancer. The strength of epidemiologic evidence was graded as high, moderate, or weak, by applying prespecified criteria that included the random effects estimate, its 95% confidence interval, and P value, estimates of heterogeneity, small-study effects, and robustness to unmeasured confounding. RESULTS This study critically appraised 277 estimates derived from 24 published meta-analyses and our own meta-analyses. The association between pediatric-onset IBDs and overall risk of cancer showed high epidemiologic evidence. Twenty associations (15 cancer types) demonstrated moderate evidence: any cancer (pediatric-onset UC), mouth to terminal ileum (CD), small bowel (CD/UC), colon (CD), rectum (CD/UC), colon-rectum (IBDs, pediatric-onset CD/UC), bile ducts and liver (CD/UC), liver (CD), intrahepatic cholangiocarcinoma (IBDs), bile ducts (CD), skin (CD), squamous cell carcinoma of the skin (CD), nonmelanoma skin cancer (UC), kidney (CD), and thyroid cancer (IBDs). Another 40 associations (23 cancer types) showed statistical significance; however, our confidence in these effect estimates was weak. No statistical significance was found regarding further 47 associations. CONCLUSIONS Associations between IBDs and different types of malignancy showed varying levels of evidence and magnitude of risk. Further primary research investigating the impact of a consistent set of risk factors that are known to affect cancer risk is warranted. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42021254996.
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Affiliation(s)
- Daniele Piovani
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Cesare Hassan
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Alessandro Repici
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Lorenza Rimassa
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Carmelo Carlo-Stella
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Georgios K Nikolopoulos
- Laboratory of Medical Statistics, Epidemiology and Public Health, Medical School, University of Cyprus, Nicosia, Cyprus
| | - Elio Riboli
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
| | - Stefanos Bonovas
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
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Robertson AR, Webster KL. Disease Activity in the Final Years of Life for Patients with Long-standing Inflammatory Bowel Disease. J Crohns Colitis 2022; 16:1340-1341. [PMID: 35255142 DOI: 10.1093/ecco-jcc/jjac039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
| | - Kirstin L Webster
- Intensive Care Unit, Western General Hospital, Edinburgh EH4 2XU, UK
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Sun J, Fang F, Olén O, Song M, Halfvarson J, Roelstraete B, Khalili H, Ludvigsson JF. Normal gastrointestinal mucosa at biopsy and subsequent cancer risk: nationwide population-based, sibling-controlled cohort study. BMC Cancer 2022; 22:890. [PMID: 35964121 PMCID: PMC9375922 DOI: 10.1186/s12885-022-09992-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 08/10/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND While individuals with normal gastrointestinal (GI) mucosa on endoscopy have a lower risk of colorectal cancer, risks of other cancers remain unexplored. METHODS Through Sweden's 28 pathology departments, we identified 415,092 individuals with a first GI biopsy with histologically normal mucosa during 1965-2016 and no prior cancer. These individuals were compared to 1,939,215 matched reference individuals from the general population. Follow-up began 6 months after biopsy, and incident cancer data were retrieved from the Swedish Cancer Register. Flexible parametric model was applied to estimate cumulative incidences and hazard ratios (HRs) for cancers. We also used full siblings (n = 441,534) as a secondary comparison group. RESULTS During a median follow-up of 10.9 years, 40,935 individuals with normal mucosa (incidence rate: 82.74 per 10,000 person-years) and 177,350 reference individuals (incidence rate: 75.26) developed cancer. Restricting the data to individuals where follow-up revealed no cancer in the first 6 months, we still observed an increased risk of any cancer in those with a histologically normal mucosa (average HR = 1.07; 95%CI = 1.06-1.09). Although the HR for any and specific cancers decreased shortly after biopsy, we observed a long-term excess risk of any cancer, with an HR of 1.08 (95%CI = 1.05-1.12) and a cumulative incidence difference of 0.93% (95%CI = 0.61%-1.25%) at 30 years after biopsy. An elevated risk of gastric cancer, lung cancer, and hematological malignancy (including lymphoproliferative malignancy) was also observed at 20 or 30 years since biopsy. Sibling analyses confirmed the above findings. CONCLUSION Individuals with a histologically normal mucosa at biopsy and where follow-up revealed no cancer in the first 6 months, may still be at increased risk of cancer, although excess risks are small.
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Affiliation(s)
- Jiangwei Sun
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Fang Fang
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Ola Olén
- Department of Medicine Solna, Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden
- Sachs' Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden
- Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
| | - Mingyang Song
- Departments of Epidemiology and Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Jonas Halfvarson
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Bjorn Roelstraete
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77, Stockholm, Sweden
| | - Hamed Khalili
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
| | - Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77, Stockholm, Sweden.
- Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
- Department of Medicine, Division of Digestive and Liver Disease, Columbia University Medical Center, New York, NY, USA.
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47
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Kumar S, Pollok R, Goldsmith D. Renal and Urological Disorders Associated With Inflammatory Bowel Disease. Inflamm Bowel Dis 2022:6658535. [PMID: 35942657 PMCID: PMC10393213 DOI: 10.1093/ibd/izac140] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Indexed: 12/15/2022]
Abstract
Renal and urinary tract complications related to inflammatory bowel disease (IBD) have been relatively understudied in the literature compared with other extraintestinal manifestations. Presentation of these renal manifestations can be subtle, and their detection is complicated by a lack of clarity regarding the optimal screening and routine monitoring of renal function in IBD patients. Urolithiasis is the most common manifestation. Penetrating Crohn's disease involving the genitourinary system as an extraintestinal complication is rare but associated with considerable morbidity. Some biologic agents used to treat IBD have been implicated in progressive renal impairment, although differentiating between drug-related side effects and deteriorating kidney function due to extraintestinal manifestations can be challenging. The most common findings on renal biopsy of IBD patients with renal injury are tubulointerstitial nephritis and IgA nephropathy, the former also being associated with drug-induced nephrotoxicity related to IBD medication. Amyloidosis, albeit rare, must be diagnosed early to reduce the chance of progression to renal failure. In this review, we evaluate the key literature relating to renal and urological involvement in IBD and emphasize the high index of suspicion required for the prompt diagnosis and treatment of these manifestations and complications, considering the potential severity and implications of acute or chronic loss of renal function. We also provide suggestions for future research priorities.
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Affiliation(s)
- Shankar Kumar
- Centre for Medical Imaging, University College London, London, UK
| | - Richard Pollok
- Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK
| | - David Goldsmith
- Renal and Transplantation Department, Guys and St Thomas' Hospitals NHS Foundation Trust, Great Maze Pond, London, UK
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Chang Z, Zhang Y, Fan J, Zhang L, Liu S, Liu G, Tu J. The potential effects and mechanisms of breast inflammatory lesions on the occurrence and development of breast cancer. Front Oncol 2022; 12:932743. [PMID: 35992864 PMCID: PMC9389363 DOI: 10.3389/fonc.2022.932743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 06/30/2022] [Indexed: 12/24/2022] Open
Abstract
Breast cancer as the most common cancer in women has become the leading cause of cancer death for women. Although many inflammatory factors increase the risk of breast cancer, there are very few studies on the mechanisms by which inflammation affects the initiation and progression of breast cancer. Here, we profiled and compared the transcriptome of normal tissues, inflammatory breast tissues, benign breast tumors, and malignant breast tumors. To find key regulatory factors, a protein interaction network between characteristic modules in inflammatory lesions and ER-negative (ER−) breast cancer was constructed and inflammation-cancer interface genes were identified. We found that the transcriptional profile of inflammatory breast tissues was similar with ER− malignant tumors, featured with low ER expression levels and similar immune signaling pathway activation. Through comprehensive protein network analysis, we identified the interface genes and chemokine signaling pathway that have the potential to promote inflammatory cancer transformation. These interface genes could be used as a risk factor to provide a certain basis for the clinical early detection and treatment of breast cancer. This is the first study to explore the association between breast inflammatory lesions and breast cancer at the transcriptome level. Our inflammation data and research results provide a basis for future inflammation-cancer transformation analysis.
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Affiliation(s)
- Zhaoxia Chang
- Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Cancer Institutes, Key Laboratory of Breast Cancer in Shanghai, The Shanghai Key Laboratory of Medical Epigenetics, Shanghai Key Laboratory of Radiation Oncology, The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ying Zhang
- Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jue Fan
- Singleron Biotechnologies, Nanjing, China
| | - Lixing Zhang
- Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Cancer Institutes, Key Laboratory of Breast Cancer in Shanghai, The Shanghai Key Laboratory of Medical Epigenetics, Shanghai Key Laboratory of Radiation Oncology, The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Suling Liu
- Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Cancer Institutes, Key Laboratory of Breast Cancer in Shanghai, The Shanghai Key Laboratory of Medical Epigenetics, Shanghai Key Laboratory of Radiation Oncology, The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Shanghai Medical College, Fudan University, Shanghai, China
- *Correspondence: Juchuanli Tu, ; Guangyu Liu, ; Suling Liu,
| | - Guangyu Liu
- Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- *Correspondence: Juchuanli Tu, ; Guangyu Liu, ; Suling Liu,
| | - Juchuanli Tu
- Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Cancer Institutes, Key Laboratory of Breast Cancer in Shanghai, The Shanghai Key Laboratory of Medical Epigenetics, Shanghai Key Laboratory of Radiation Oncology, The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Shanghai Medical College, Fudan University, Shanghai, China
- *Correspondence: Juchuanli Tu, ; Guangyu Liu, ; Suling Liu,
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Zafari N, Khosravi F, Rezaee Z, Esfandyari S, Bahiraei M, Bahramy A, Ferns GA, Avan A. The role of the tumor microenvironment in colorectal cancer and the potential therapeutic approaches. J Clin Lab Anal 2022; 36:e24585. [PMID: 35808903 PMCID: PMC9396196 DOI: 10.1002/jcla.24585] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 06/07/2022] [Accepted: 06/23/2022] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Colorectal cancer (CRC) with a high prevalence is recognized as the fourth most common cause of cancer-related death globally. Over the past decade, there has been growing interest in the network of tumor cells, stromal cells, immune cells, blood vessel cells, and fibroblasts that comprise the tumor microenvironment (TME) to identify new therapeutic interventions. METHODS Databases, such as Google Scholar, PubMed, and Scopus, were searched to provide an overview of the recent research progress related to targeting the TME as a novel therapeutic approach. RESULTS Tumor microenvironment as a result of the cross talk between these cells may result in either advantages or disadvantages in tumor development and metastasis, affecting the signals and responses from the surrounding cells. Whilst chemotherapy has led to an improvement in CRC patients' survival, the metastatic aspect of the disease remains difficult to avoid. CONCLUSIONS The present review emphasizes the structure and function of the TME, alterations in the TME, its role in the incidence and progression of CRC, the effects on tumor development and metastasis, and also the potential of its alterations as therapeutic targets. It should be noted that providing novel studies in this field of research might help us to achieve practical therapeutic strategies based on their interaction.
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Affiliation(s)
- Narges Zafari
- Department of Medical Genetics, School of MedicineTehran University of Medical SciencesTehranIran
| | - Fatemeh Khosravi
- Molecular Medicine Research Center, Hormozgan Health InstituteHormozgan University of Medical SciencesBandar AbbasIran
| | - Zahra Rezaee
- Department of Medical Genetics, Faculty of Medical SciencesTarbiat Modares UniversityTehranIran
| | - Sahar Esfandyari
- Department of Anatomy, School of MedicineTehran University of Medical SciencesTehranIran
| | - Mohamad Bahiraei
- Department of Radiology, Besat HospitalHamedan University of Medical SciencesHamedanIran
| | - Afshin Bahramy
- Department of Medical Genetics, Faculty of Medical SciencesTarbiat Modares UniversityTehranIran
| | - Gordon A. Ferns
- Brighton & Sussex Medical SchoolDivision of Medical EducationSussexUK
| | - Amir Avan
- Metabolic Syndrome Research CenterMashhad University of Medical SciencesMashhadIran
- Basic Medical Sciences InstituteMashhad University of Medical SciencesMashhadIran
- Medical Genetics Research CenterMashhad University of Medical SciencesMashhadIran
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50
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Cost-Effectiveness of Therapeutic Drug Monitoring of Anti-TNF Therapy in Inflammatory Bowel Disease: A Systematic Review. Pharmaceutics 2022; 14:pharmaceutics14051009. [PMID: 35631594 PMCID: PMC9145467 DOI: 10.3390/pharmaceutics14051009] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 04/27/2022] [Accepted: 04/30/2022] [Indexed: 02/01/2023] Open
Abstract
Infliximab and adalimumab are monoclonal antibodies against tumor necrosis factor (anti-TNF) used to manage inflammatory bowel disease (IBD). Therapeutic Drug Monitoring (TDM) has been proven to prevent immunogenicity, to achieve better long-term clinical results and to save costs in IBD treatment. The aim of this study was to conduct a systematic review on cost-effectiveness analyses of studies that apply TDM of anti-TNF in IBD and to provide a critical analysis of the best scientific knowledge available in the literature. The quality of the included studies was assessed using Consolidated Health Economic Evaluation Reporting Standards (CHEERS). Cost-effectiveness of the TDM strategies was presented as total costs, cost savings, quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER). Thirteen studies that examined the health economics of TDM of anti-TNF in IBD from 2013 to 2021 were included. Eight of them (61.5%) achieved a score between 17 and 23 on the CHEERS checklist. The comparison between the TDM strategy and an empirical strategy was cost saving. The ICER between reactive TDM and an empirical strategy was dominated (favorable) by reactive TDM, whereas the ICER value for proactive TDM compared to an empirical strategy ranged from EUR 56,845 to 3,901,554. This systematic review demonstrated that a TDM strategy is cost-effective or cost-saving in IBD.
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