Systematic review of reported association studies of monogenic genes and bladder cancer risk and confirmation analysis in a large population cohort

Objectives To evaluate which of previously reported monogenic genes are associated with increased bladder cancer risk, we reviewed published papers on associations of genes and bladder cancer risk and performed a confirmation study of these genes in a large population‐based cohort. Subjects and methods A systematic review of published papers prior to June 2022 was performed first to identify all genes where germline mutations were associated with bladder cancer risk. The associations of these candidate genes with bladder cancer risk were then tested among 1695 bladder cancer cases and 186 271 controls in the UK Biobank (UKB). The robust SKAT‐O, a gene‐based analysis that properly controls for type I error rates due to unbalanced case–control ratio, was used for association tests adjusting for age at recruitment, gender, smoking status, and genetic background. Results The systematic review identified nine genes that were significantly associated with bladder cancer risk in at least one study (p