Assessing the contribution of rare protein-coding germline variants to prostate cancer risk and severity in 37,184 cases.

ABSTRACT: To assess the contribution of rare coding germline genetic variants to prostate cancer risk and severity, we perform here a meta-analysis of 37,184 prostate cancer cases and 331,329 male controls from five cohorts with germline whole exome or genome sequencing data, and one cohort with imputed array data. At the gene level, our case-control collapsing analysis confirms associations between rare damaging variants in four genes and increased prostate cancer risk: SAMHD1, BRCA2 and ATM at the study-wide significance level (P < 1×10^-8), and CHEK2 at the suggestive threshold (P < 2.6×10^-6). Our case-only analysis, reveals that rare damaging variants in AOX1 are associated with more aggressive disease (OR = 2.60 [1.75-3.83], P = 1.35×10^-6), as well as confirming

SUBMITTER: Mitchell J 

PROVIDER: S-EPMC11839991 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature