Rare germline variants in DNA repair genes and the angiogenesis pathway predispose prostate cancer patients to develop metastatic disease.

ABSTRACT:

Background

Prostate cancer (PrCa) demonstrates a heterogeneous clinical presentation ranging from largely indolent to lethal. We sought to identify a signature of rare inherited variants that distinguishes between these two extreme phenotypes.

Methods

We sequenced germline whole exomes from 139 aggressive (metastatic, age of diagnosis < 60) and 141 non-aggressive (low clinical grade, age of diagnosis ≥60) PrCa cases. We conducted rare variant association analyses at gene and gene set levels using SKAT and Bayesian risk index techniques. GO term enrichment analysis was performed for genes with the highest differential burden of rare disruptive variants.

Results

Protein truncating variants (PTVs) in specific DNA repair genes were significantly overrepresented among pati

SUBMITTER: Mijuskovic M 

PROVIDER: S-EPMC6035259 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature