biostudies-literatureStopsack KHNational Cancer Institute (NCI)Prostate Cancer Foundation (PCF)National Cancer InstituteNCI NIH HHSProstate Cancer Foundation122-129https://www.ebi.ac.uk/biostudies/studies/S-EPMC12407385biostudies-literatureUnknown31(1)<h4>Purpose</h4>Deleterious germline variants in certain DNA repair genes are risk factors for developing aggressive prostate cancer. The objective was to quantify their prognostic impact after prostate cancer diagnosis.<h4>Experimental design</h4>Men with prostate cancer, predominantly of European ancestry, were included from four cohorts with long-term follow-up. Pathogenic or likely pathogenic germline variants in 26 DNA repair genes were assessed in relation to metastasis-free survival in high-risk localized prostate cancer and to overall survival in metastatic castration-sensitive prostate cancer (mCSPC) and metastatic castration-resistant prostate cancer (mCRPC).<h4>Results</h4>Among 3,525 patients initially diagnosed with nonmetastatic prostate cancer, 2,594 had high-risk localized Clinical cancer research : an official journal of the American Association for Cancer ResearchGermline DNA Damage Repair Variants and Prognosis of Patients with High-Risk or Metastatic Prostate Cancer.PMC12407385P30CA06516P50 CA092629U01 CA167552U01CA167552P30 CA008748P30 CA006516P50CA092629P30CA008748P01 CA22869618CHAL05P01CA228696Vijai JBerchuck JEMandelker DKantoff PWFreeman DAOffit KKemel YMorris MJMucci LAStopsack KHPomerantz MMLee GMVasselman SEConry MPenney KLAbida WSolit DBfalseGermline DNA Damage Repair Variants and Prognosis of Patients with High-Risk or Metastatic Prostate Cancer.<h4>Purpose</h4>Deleterious germline variants in certain DNA repair genes are risk factors for developing aggressive prostate cancer. The objective was to quantify their prognostic impact after prostate cancer diagnosis.<h4>Experimental design</h4>Men with prostate cancer, predominantly of European ancestry, were included from four cohorts with long-term follow-up. Pathogenic or likely pathogenic germline variants in 26 DNA repair genes were assessed in relation to metastasis-free survival in high-risk localized prostate cancer and to overall survival in metastatic castration-sensitive prostate cancer (mCSPC) and metastatic castration-resistant prostate cancer (mCRPC).<h4>Results</h4>Among 3,525 patients initially diagnosed with nonmetastatic prostate cancer, 2,594 had high-risk localized 2025-01-01T00:00:00Z2025 Jan2026-05-29T21:38:37.72Z2026-04-08T06:06:41.086ZS-EPMC124073853945070410.1158/1078-0432.ccr-24-248310.1158/1078-0432.CCR-24-2483