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

PeerJ

article

Bangbei Wan¹  Ning Ma¹  Weiying Lu¹ 

[1] Reproductive Medical Center, Hainan Women and Children’s Medical Center;Department of Urology, Central South University Xiangya School of Medicine Affiliated Haikou Hospital

关键词: Bladder cancer;    Body fat mass;    Mendelian randomization;    Genome-wide association study;    Single-nucleotide polymorphisms;   

DOI  :  10.7717/peerj.14739

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundObservational 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.MethodsSingle-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.ResultsGenetically 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.ConclusionsOur 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.

【 授权许可】

CC BY