Association between long-term benzene exposure and inflammatory bowel disease in a national cohort: The modifying effect of genetic susceptibility

Abstract

Background: This study aimed to investigate the effects of environmental benzene exposure and its interaction with genetic susceptibility on inflammatory bowel disease (IBD), with a specific focus on ulcerative colitis (UC) and Crohn's disease (CD).

Methods: A total of 432,727 participants from the UK Biobank who were free of IBD at baseline were included in the analysis. The annual average benzene concentrations during the follow-up period were evaluated by air dispersion models. The study assessed the incidence of IBD in relation to ambient benzene exposure using Cox proportional hazard models and estimated the exposureresponse relationships using restricted cubic spline models. Additive interactions included relative excess risk due to interaction (RERI) and the attributable proportion (AP) to evaluate the interaction between ambient benzene exposure and genetic predisposition.

Results: A significant association was identified between ambient benzene exposure and the incidence of IBD, with hazard ratios (95 % confidence intervals) of 1.06 (1.03, 1.09) for IBD, 1.08 (1.04, 1.12) for UC, and 1.03 (0.98, 1.09) for CD per 0.1 μg/m³ increase. Furthermore, genetic predispositions were found to significantly modify the relationship between ambient benzene exposure and IBD risk. Individuals with the highest genetic risk and benzene exposure had the highest risk of UC.

Conclusion: This study provides compelling evidence of the interaction between environmental factors and genetic susceptibility in the pathogenesis of UC. These findings underscore the importance of considering both genetic and environmental influences in future prevention and intervention strategies for IBD.

Keywords: Air pollution; Benzene; Genetic susceptibility; Inflammatory bowel disease.