{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T07:06:45Z","timestamp":1788937605840,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      We previously developed a tier\u2010based germline classification using the National Comprehensive Cancer Network (NCCN)\u2010recommended DNA damage repair (DDR) genes and\n                      <jats:italic>KLK3<\/jats:italic>\n                      I179T to predict prostate cancer (PCa)\u2010specific mortality (PCSM). To provide an easier\u2010to\u2010use single inherited risk score while preserving gene\u2010specific effects, we developed GenProb\u2010PCSM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed 14,644 men with incident PCa from the UK Biobank. The cohort was randomly divided into training (60%) and independent testing (40%) datasets. GenProb\u2010PCSM was developed in the training cohort by integrating pathogenic variants in ten NCCN\u2010recommended DDR genes and the\n                      <jats:italic>KLK3<\/jats:italic>\n                      I179T variant using gene\u2010specific weights derived from Fine\u2013Gray competing\u2010risk models. Performance was evaluated in the independent testing cohort by discrimination, calibration, and risk stratification. Secondary analyzes evaluated metastatic progression and the composite endpoint of metastatic progression and\/or PCSM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 14,644 men with incident PCa, 1,581 died from PCa. GenProb\u2010PCSM remained significantly associated with PCSM in the independent testing cohort (HR per SD, 1.18; 95% CI, 1.12\u20131.24;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Using predefined risk thresholds derived from the training cohort, patients in the intermediate\u2010 and high\u2010risk groups had significantly increased risks of PCSM compared with the low\u2010risk group (HR 1.49, 95% CI 1.22\u20131.84; and HR 4.04, 95% CI 2.58\u20136.33, respectively). GenProb\u2010PCSM also predicted independent metastatic progression and the composite endpoint of metastatic progression and\/or PCSM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>GenProb\u2010PCSM transforms complex germline findings into a single inherited risk score for PCSM and metastatic progression. Its simplicity and preservation of gene\u2010specific effects may facilitate clinical implementation of germline prognostic assessment in PCa.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.70244","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T06:25:27Z","timestamp":1788935127000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["GenProb\u2010PCSM: A Simplified Weighted Germline Score for Prostate Cancer\u2010Specific Mortality"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9778-1239","authenticated-orcid":false,"given":"Jun","family":"Wei","sequence":"first","affiliation":[{"name":"Program for Genomic Translational Research Endeavor Health Evanston Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuqing","family":"Shi","sequence":"additional","affiliation":[{"name":"Program for Genomic Translational 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huy","family":"Tran","sequence":"additional","affiliation":[{"name":"Program for Genomic Translational Research Endeavor Health Evanston Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabelle","family":"Ashworth","sequence":"additional","affiliation":[{"name":"Program for Genomic Translational Research Endeavor Health Evanston Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Lilly Zheng","sequence":"additional","affiliation":[{"name":"Program for Genomic Translational Research Endeavor Health Evanston Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6629-4011","authenticated-orcid":false,"given":"Alan R.","family":"Sanders","sequence":"additional","affiliation":[{"name":"Genomic Health Initiative Endeavor Health Evanston Illinois USA"},{"name":"University of Chicago Pritzker School of 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