Association between inflammatory bowel disease and the risk of parenteral malignancies: A two-sample Mendelian randomization study

ABSTRACT

Abstract Aim: Using Mendelian Randomization (MR) analysis to investigate the potential causal association between Inflammatory Bowel Disease (IBD) and the occurrence of parenteral malignancies, in order to provide some reference for the parenteral malignancy prevention in patients with IBD. Methods: This was a two-sample MR study based on independent genetic variants strongly linked to IBD selected from the Genome-Wide Association Study (GWAS) meta-analysis carried out by the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). Parenteral malignancy cases and controls were obtained from the FinnGen consortium and the UK Biobank (UKB) release data. Inverse Variance Weighted (IVW), weighted median, MR-Egger, and strength test (F) were utilized to explore the causal association of IBD with parenteral malignancies. In addition, Cochran's Q statistic was performed to quantify the heterogeneity of Instrumental Variables (IVs). Results: The estimates of IVW showed that patients with IBD had higher odds of diffuse large B-cell lymphoma (OR = 1.2450, 95% CI 1.0311‒1.5034). UC had potential causal associations with non-melanoma skin cancer (all p < 0.05), melanoma (OR = 1.0280, 95% CI 0.9860‒1.0718), and skin cancer (OR = 1.0004, 95% CI 1.0001‒1.0006). Also, having CD was associated with higher odds of non-melanoma skin cancer (all p < 0.05) and skin cancer (OR = 1.0287, 95% CI 1.0022‒1.0559). In addition, results of pleiotropy and heterogeneity tests indicated these results are relatively robust. Conclusions: IBD has potential causal associations with diffuse large B-cell lymphoma and skin cancers, which may provide some information on the prevention of parenteral malignancies in patients with IBD. Moreover, further studies are needed to explore the specific mechanisms of the effect of IBD on skin cancers.