Risk of Cancer in Inflammatory Bowel Diseases: Umbrella Review and Reanalysis of Meta-analyses

Daniele Piovani; Cesare Hassan; Alessandro Repici; Lorenza Rimassa; Carmelo Carlo-Stella; Georgios K Nikolopoulos; Elio Riboli; Stefanos Bonovas

doi:10.1053/j.gastro.2022.05.038

Risk of Cancer in Inflammatory Bowel Diseases: Umbrella Review and Reanalysis of Meta-analyses

Gastroenterology. 2022 Sep;163(3):671-684. doi: 10.1053/j.gastro.2022.05.038. Epub 2022 May 26.

Authors

Daniele Piovani¹, Cesare Hassan², Alessandro Repici², Lorenza Rimassa³, Carmelo Carlo-Stella³, Georgios K Nikolopoulos⁴, Elio Riboli⁵, Stefanos Bonovas⁶

Affiliations

¹ Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
² Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
³ Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
⁴ Laboratory of Medical Statistics, Epidemiology and Public Health, Medical School, University of Cyprus, Nicosia, Cyprus.
⁵ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
⁶ Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. Electronic address: stefanos.bonovas@hunimed.eu.

PMID: 35643170
DOI: 10.1053/j.gastro.2022.05.038

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.

Keywords: Inflammation; Intestine; Neoplasms; Pathogenesis; Summary.

Publication types

Systematic Review

MeSH terms

Child
Colitis, Ulcerative* / diagnosis
Colitis, Ulcerative* / epidemiology
Crohn Disease* / diagnosis
Crohn Disease* / epidemiology
Humans
Inflammatory Bowel Diseases* / epidemiology
Meta-Analysis as Topic
Neoplasms* / epidemiology
Neoplasms* / etiology

Supplementary concepts

Pediatric ulcerative colitis