{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T03:31:38Z","timestamp":1787196698412,"version":"build-2736575974"},"reference-count":61,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Approximately 50% of prostate cancer (PCa) patients meet the National Comprehensive Cancer Network (NCCN) guidelines for germline testing at diagnosis. However, the selection of genes for testing, their supporting evidence, and clinical interpretation remain poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An evidence\u2010based evaluation of the recommended genes was conducted using data from the UK Biobank and Johns Hopkins School of Medicine, including 22,052 PCa patients and 191,055 unaffected controls. Association of germline pathogenic\/likely pathogenic (P\/LP) variants in each gene was tested using logistic regression, adjusting for age and genetic background.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the 11 NCCN\u2010recommended PCa\u2010related genes, significant associations (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0045) were identified between germline P\/LP variants of five genes (<jats:italic>HOXB13, BRCA2, ATM, CHEK2<\/jats:italic>, and <jats:italic>MSH2<\/jats:italic>) and PCa risk. Additionally, <jats:italic>BRCA2<\/jats:italic> and <jats:italic>ATM<\/jats:italic> variants were significantly associated with PCa aggressiveness. Of the 19 NCCN\u2010recommended genes related to PARPi sensitivity, consistent evidence supported an enhanced response to PARPi therapy in patients with <jats:italic>BRCA2<\/jats:italic> alterations, with weaker evidence for <jats:italic>BRCA1<\/jats:italic>, and limited supporting evidence for the remaining genes. Germline P\/LP variants in <jats:italic>BRCA2<\/jats:italic> and <jats:italic>BRCA1<\/jats:italic> were observed in 0.77% and 0.14% of unselected PCa patients, respectively. Notably, no published study specifically assessed the efficacy of germline alterations, which were considerably rarer than somatic mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Supporting statistical evidence is available for only a subset of the NCCN\u2010recommended genes for germline testing. This evidence\u2010based analysis may aid urologists\u2014particularly those without specialized genetics training\u2014in understanding germline testing for PCa risk assessment, prognosis, and treatment decision\u2010making in clinical practice.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.24918","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T02:44:48Z","timestamp":1747968288000},"page":"1087-1095","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Germline Testing for Prostate Cancer Patients: Evidence\u2010Based Evaluation of Genes Recommended by NCCN Guidelines"],"prefix":"10.1002","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9419-6627","authenticated-orcid":false,"given":"Jianfeng","family":"Xu","sequence":"first","affiliation":[{"name":"Program for Genomic Translational Research, Endeavor Health Evanston Illinois USA"},{"name":"Division of Urology, 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