Risk of intestinal cancer in Crohn's disease: re-analysis and meta-regression of population-based cohort studies

The risk of intestinal malignancy in Crohn's disease (CD) varies across regions. Given the rising global cancer prevalence, this study aimed to summarize evidence and evaluate associations between CD and site-specific intestinal cancer risks.

We systematically searched PubMed, Embase, and Scopus from inception to July 10, 2025. All population-based epidemiological observational studies that investigated any outcome related to intestinal cancer in adults (the majority of participants >18 years of age), including individuals of any ethnicity or sex from all countries and settings that report observed and expected national cases, were included. Patients diagnosed with colorectal cancer (CRC) or small bowel cancer (SBC) less than 1 year after CD diagnosis, as well as papers that address cancer mortality while combining CD and ulcerative colitis outcomes, referral-center studies, and review articles, were excluded. We analyzed 27 population-based studies using restricted maximum-likelihood models; pooled standardized incidence ratios (SIRs) were calculated for CRC and SBC. Meta-regression explored the impact of cohort size, follow-up duration, calendar year, and disease location on risk estimates. Methodological quality was assessed with the modified Newcastle-Ottawa Scale.

The overall CRC SIR in CD patients was significantly elevated (SIR 2.20, 95% CI 1.69-2.86). Colon cancer (SIR 2.06, 95% CI 1.09-3.90) and rectal cancer (SIR 1.75, 95% CI 1.16-2.62) risks were higher, especially in colonic disease (SIR 3.29, 95% CI 1.66-6.50) and ileocolonic disease (SIR 4.13, 95% CI 2.14-7.94), while ileal disease exposed a milder risk (SIR 1.95, 95% CI 1.16-3.26). SBC SIR was markedly increased (SIR 17.18, 95% CI 9.93-29.73), particularly in ileal (SIR 44.85, 95% CI 12.93-155.54) and ileocolonic disease (SIR 21.44, 95% CI 5.13-89.62).

CD is associated with heightened CRC and SBC risks, varying by disease location. These findings underscore the need for tailored cancer screening and further research into the impact of environmental and genetic factors on cancer risk in CD patients.