Global, Population and Genetic Evidence on the Relationships Between Immune-Mediated Inflammatory Disease and Cancer Risk.

Background: Immune-mediated inflammatory disease (IMID) and cancer share underlying mechanisms. We aimed to comprehensively evaluate the associations between IMIDs and cancers from global, population and genetic perspectives. Methods: A triangulation framework was employed to assess the association between IMIDs and cancers, using the Global Burden of Disease Study (2012-2021) to analyse six IMIDs and 33 cancers. The UK Biobank (UKBB) prospective cohort was subsequently used to validate these associations, with hazard ratios (HRs) and 95% confidence intervals (CIs) estimated by Cox proportional hazards models. Causal inference based on genetic instruments was performed in the FinnGen and UKBB to assess the potential causal effects between IMIDs and cancers. Results: IMIDs were positively associated with the occurrence of cancers from a global perspective. Moreover, 170 specific IMID-cancer pairs revealed statistically significant associations. A total of 20 pairs of specific IMID-cancer associations were further confirmed in the UKBB cohort. Among these, the five most pronounced associations included atopic dermatitis with Hodgkin lymphoma (HR = 12.56, 95% CI: 1.76-89.59), with ovarian cancer (HR = 5.65, 95% CI: 1.41-22.65) and with non-Hodgkin lymphoma (HR = 5.11, 95% CI: 1.91-13.63); rheumatoid arthritis with Hodgkin lymphoma (HR = 3.85, 95% CI: 1.11-13.32); and psoriasis with Hodgkin lymphoma (HR = 3.43, 95% CI: 1.69-6.96). Additionally, a positive causal association between rheumatoid arthritis and Hodgkin lymphoma (inverse variance weighted OR = 1.31, 95% CI: 1.10-1.57) was observed. Conclusions: This study provides comprehensive evidence of the relationships between IMIDs and cancers from global, population and genetic perspectives and identifies 20 pairs of specific IMID-cancer associations, thereby contributing to advancements in cancer prevention and control.