Inflammatory Bowel Disease and Long-term Risk of Cancer: A Prospective Cohort Study Among Half a Million Adults in UK Biobank

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 WC]; 1449 Crohn's disease ICDI; 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. Lay Summary Regardless of IBD subtype, IBD may be associated with a 17% excess risk of incident overall cancer and a 26% higher risk of death due to cancer compared with non-IBD participants-and the risk seemed even higher in UC patients.