Mendelian randomization investigation identified the causal relationship between body fat indexes and the risk of...

Observational studies have suggested that obesity is associated with the risk of bladder cancer (BCa). However, their causal relationship remains unclear. This study aimed to prove the causal relationship between obesity and the risk of BCa by using Mendelian randomization.

Single-nucleotide polymorphisms (SNPs) correlated with body fat indexes were screened from several genome-wide association studies (GWAS) with more than 300,000 individuals. Summary-level genetic data of BCa-related GWAS were obtained from a European cohort with a sample size of 218,792. An inverse-variance-weighted (IVW) method was used as the major MR analysis. The MR-Egger regression, IVW regression, leave-one-out test, and MR-Pleiotropy Residual Sum and Outlier methods were used to test the reliability and stability of MR results.

Genetically predicted per 1-SD increase in body fat indexes (whole body fat mass, and the right leg, left leg, right arm, left arm, and trunk fat mass) were associated with increased BCa risk with values of 51.8%, 77.9%, 75.1%, 67.2%, 59.7%, and 36.6%, respectively. Sensitivity analyses suggested that the genetically determined risk effect of obesity on BCa was stable and reliable.

Our study provided powerful evidence to support the causal hypothesis that the genetically predicted high body fat mass was associated with a risk increase for BCa. The finding is a new idea for drawing up prevention strategies for BCa.