Whole exome sequencing in 75 high-risk families with validation and replication in independent case-control studies identifies TANGO2, OR5H14, and CHAD as new prostate cancer susceptibility genes.

ABSTRACT: Prostate cancer (PCa) susceptibility is defined by a continuum from rare, high-penetrance to common, low-penetrance alleles. Research to date has concentrated on identification of variants at the ends of that continuum. Taking an alternate approach, we focused on the important but elusive class of low-frequency, moderately penetrant variants by performing disease model-based variant filtering of whole exome sequence data from 75 hereditary PCa families. Analysis of 341 candidate risk variants identified nine variants significantly associated with increased PCa risk in a population-based, case-control study of 2,495 men. In an independent nested case-control study of 7,121 men, there was risk association evidence for TANGO2 p.Ser17Ter and the established HOXB13 p.Gly84Glu variant. Meta-anal

SUBMITTER: Karyadi DM 

PROVIDER: S-EPMC5341753 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature