Autoimmune diseases and the risk of bladder cancer: A Mendelian randomization analysis

Abstract

Objective: To investigate the association between autoimmune diseases (AIDs) and bladder cancer (BC) at the genetic level using Mendelian randomization (MR).

Methods: Single nucleotide polymorphisms (SNPs) associated with the seven AIDs were extracted from the IEU GWAS database, and the SNPs were quality-controlled using strict screening criteria. The association between AIDs and BC risk was assessed by inverse-variance weighted (IVW), MR-Egger regression and Weighted median method. The heterogeneity of SNPs was evaluated by Cochran Q test. MR-Egger intercept test and MR-PRESSO global test were used to test the horizontal pleiotropy of SNPs. Both sides with potential causal associations were validated using the validation set.

Results: Our result showed that genetically predicted RA was significantly associated with an increased risk of BC (IVW OR = 1.214, 95 % CI = 1.062-1.388, P = 0.005). MS nominally increased the risk of BC (IVW OR = 1.095, 95 % CI = 1.005-1.193, P = 0.037), consistent with the results of the MR analysis of the BC validation cohort. However SLE, T1D, UC, CD, and MG were not causally associated with BC risk (P > 0.05). The sensitivity analyses showed that there was no heterogeneity or horizontal pleiotropy in our findings.

Conclusion: This study provides evidence of a causal relationship between AIDs and BC risk at the genetic level, confirming a causal relationship between RA and MS in increasing the risk of BC.

Keywords: Autoimmune diseases; Bladder cancer; Genetic level; Mendelian randomization.