{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T13:16:54Z","timestamp":1783603014771,"version":"3.55.0"},"reference-count":26,"publisher":"Harborside Press, LLC","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7]]},"abstract":"\n Background:<\/jats:bold>\n Pathogenic germline variant (PGV) rates in cancer risk genes and their association with clinicopathologic features inform genetic testing practices for patients with prostate cancer (PCa). In this study, we determined the rate of PGVs in PCa risk genes in a real-world, diverse cohort of patients with PCa and identified clinical predictors of carrier status.\n Patients and Methods:<\/jats:bold>\n Genetic testing results for 12 PCa risk genes, along with clinical, pathologic, and family history variables, were abstracted from 1,032 patients with PCa who met NCCN genetic testing criteria in oncology clinics, and 3,602 patients with PCa who underwent testing through the VA National Precision Oncology Program. Individual gene PGV rates in patients with PCa were compared with those in individuals assigned male at birth who were cancer-free. Statistical analyses were performed using unpaired\n t<\/jats:italic>\n tests and Fisher exact tests.\n Results:<\/jats:bold>\n Among 4,634 patients with PCa, 5.4% had PGVs, with\n BRCA2<\/jats:italic>\n (1.7%),\n ATM<\/jats:italic>\n (1.3%), and\n CHEK2<\/jats:italic>\n being the most common. The total PGV rate was significantly higher in 2,825 self-identified White and 1,527 self-identified Black patients (6.3% vs 3.7%;\n P<\/jats:italic>\n adjusted<\/jats:sub>\n =.0024), although rates of\n BRCA2<\/jats:italic>\n and\n BRCA1<\/jats:italic>\n PGVs were similar (1.9% vs 1.3%;\n P<\/jats:italic>\n adjusted<\/jats:sub>\n =.0885 and 0.6% vs 0.5%;\n P<\/jats:italic>\n adjusted<\/jats:sub>\n =.8005, respectively). PGV rates did not differ significantly between 311 self-identified Hispanic and 4,188 self-identified non-Hispanic patients (3.9% vs 5.5%;\n P<\/jats:italic>\n adjusted<\/jats:sub>\n =1.000). In self-identified White and Black patients, PGV rates in\n BRCA2<\/jats:italic>\n and Lynch syndrome genes (\n MLH1<\/jats:italic>\n ,\n MSH2<\/jats:italic>\n ,\n MSH6<\/jats:italic>\n ,\n PMS2<\/jats:italic>\n ) were significantly higher compared with a cancer-free cohort of individuals assigned male at birth. In a multivariable logistic regression, age at initial PCa diagnosis and self-identified race were significantly associated with the presence of any PGV. In this racially diverse, real-world cohort of individuals with advanced PCa meeting NCCN testing criteria, the overall PGV rate was approximately 5%. Outside of\n ATM<\/jats:italic>\n and\n CHEK2<\/jats:italic>\n , PGV rates were similar across self-identified race, self-identified ethnicity, and clinical stage.\n Conclusions:<\/jats:bold>\n These data support NCCN Guideline\u2013recommended universal genetic testing for patients with aggressive PCa.\n <\/jats:p>","DOI":"10.6004\/jnccn.2026.7006","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T13:03:46Z","timestamp":1780405426000},"source":"Crossref","is-referenced-by-count":0,"title":["Pathogenic Germline Variants in a Racially Diverse Real-World Cohort of Patients With Prostate Cancer"],"prefix":"10.6004","volume":"24","author":[{"given":"Taylor B.","family":"Crawford","sequence":"first","affiliation":[{"name":"Corporal Michael Crescenz Veterans Affairs Medical Center, Philadelphia, PA"},{"name":"Department of Medicine-Hematology\/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maliha","family":"Tayeb","sequence":"additional","affiliation":[{"name":"Department of Medicine-Hematology\/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"},{"name":"Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuel","family":"Barrett","sequence":"additional","affiliation":[{"name":"Department of Medicine-Hematology\/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Al-Saleem","sequence":"additional","affiliation":[{"name":"Corporal Michael Crescenz Veterans Affairs Medical Center, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranavi","family":"Kondam","sequence":"additional","affiliation":[{"name":"Department of Medicine-Hematology\/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Hausler","sequence":"additional","affiliation":[{"name":"Corporal Michael Crescenz Veterans Affairs Medical Center, Philadelphia, PA"},{"name":"Department of Medicine-Hematology\/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"},{"name":"Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Symecko","sequence":"additional","affiliation":[{"name":"Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin","family":"Orr","sequence":"additional","affiliation":[{"name":"Department of Medicine-Hematology\/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"},{"name":"Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine Spielman","family":"Wolfe","sequence":"additional","affiliation":[{"name":"Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Mann","sequence":"additional","affiliation":[{"name":"Department of Medicine-Hematology\/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey","family":"Spielman","sequence":"additional","affiliation":[{"name":"Department of Medicine-Hematology\/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Wong","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgical and Peri-operative Care, VA Greater Los Angeles Healthcare System, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi B.","family":"Haas","sequence":"additional","affiliation":[{"name":"Department of Medicine-Hematology\/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Narayan","sequence":"additional","affiliation":[{"name":"Department of Medicine-Hematology\/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Robinson","sequence":"additional","affiliation":[{"name":"Corporal Michael Crescenz Veterans Affairs Medical Center, Philadelphia, PA"},{"name":"Department of Medicine-Hematology\/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Takvorian","sequence":"additional","affiliation":[{"name":"Department of Medicine-Hematology\/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ning","family":"Wong","sequence":"additional","affiliation":[{"name":"Corporal Michael Crescenz Veterans Affairs Medical Center, Philadelphia, PA"},{"name":"Department of Medicine-Hematology\/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra O.","family":"Sokolova","sequence":"additional","affiliation":[{"name":"Puget Sound VA Medical Center, Seattle, WA"},{"name":"Division of Hematology\/Oncology, University of Washington School of Medicine, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B.","family":"Montgomery","sequence":"additional","affiliation":[{"name":"Puget Sound VA Medical Center, Seattle, WA"},{"name":"Division of Hematology\/Oncology, University of Washington School of Medicine, Seattle, WA"},{"name":"Fred Hutchison Cancer Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Menendez","sequence":"additional","affiliation":[{"name":"Durham VA Health System, Durham, NC"},{"name":"Department of Surgery, Duke University Medical Center, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Kelley","sequence":"additional","affiliation":[{"name":"Durham VA Health System, Durham, NC"},{"name":"Division of Medical Oncology, Duke University School of Medicine, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa B.","family":"Aiello","sequence":"additional","affiliation":[{"name":"Corporal Michael Crescenz Veterans Affairs Medical Center, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isla P.","family":"Garraway","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgical and Peri-operative Care, VA Greater Los Angeles Healthcare System, Los Angeles, CA"},{"name":"Department of Urology, University of California Los Angeles, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Domchek","sequence":"additional","affiliation":[{"name":"Department of Medicine-Hematology\/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"},{"name":"Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara N.","family":"Maxwell","sequence":"additional","affiliation":[{"name":"Corporal Michael Crescenz Veterans Affairs Medical Center, Philadelphia, PA"},{"name":"Department of Medicine-Hematology\/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"},{"name":"Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4047","reference":[{"key":"B1","series-title":"Prostate","first-page":"S3","article-title":"Germline genetics of prostate cancer","volume":"82","author":"Khan HM","year":"2022","unstructured":"Khan HM, Cheng HH. 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Fam Cancer 2022;21:101\u2013114."},{"key":"B4","series-title":"Nat Rev Urol","first-page":"18","article-title":"The genetic epidemiology of prostate cancer and its clinical implications","volume":"11","author":"Eeles R","year":"2014","unstructured":"Eeles R, Goh C, Castro E, The genetic epidemiology of prostate cancer and its clinical implications. Nat Rev Urol 2014;11:18\u201331."},{"key":"B5","article-title":"NCCN Clinical Practice Guidelines in Oncology: Genetic\/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, and Prostate. Version 3.2026","author":"Daly MB","unstructured":"Daly MB, Pal T, AlHilli Z, NCCN Clinical Practice Guidelines in Oncology: Genetic\/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, and Prostate. Version 3.2026. Accessed April 13, 2026. 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Nat Med 2025;31:4109\u20134118."},{"key":"B8","series-title":"Curr Oncol Rep","first-page":"533","article-title":"PARP inhibitors in the neoadjuvant setting; a comprehensive overview of the rationale for their use, past and ongoing clinical trials","volume":"27","author":"Habaka M","year":"2025","unstructured":"Habaka M, Daly GR, Shinyanbola D, PARP inhibitors in the neoadjuvant setting; a comprehensive overview of the rationale for their use, past and ongoing clinical trials. Curr Oncol Rep 2025;27:533\u2013551."},{"key":"B9","series-title":"JAMA Oncol","first-page":"1272","article-title":"BRCA1, BRCA2, and associated cancer risks and management for male patients: a review","volume":"10","author":"Cheng HH","year":"2024","unstructured":"Cheng HH, Shevach JW, Castro E, BRCA1, BRCA2, and associated cancer risks and management for male patients: a review. JAMA Oncol 2024;10:1272\u20131281."},{"key":"B10","series-title":"J Natl Cancer Inst","first-page":"616","article-title":"Germline sequencing DNA repair genes in 5545 men with aggressive and nonaggressive prostate cancer","volume":"113","author":"Darst BF","year":"2021","unstructured":"Darst BF, Dadaev T, Saunders E, Germline sequencing DNA repair genes in 5545 men with aggressive and nonaggressive prostate cancer. J Natl Cancer Inst 2021;113:616\u2013625."},{"key":"B11","series-title":"JCO Precis Oncol","first-page":"e2200104","article-title":"Internet-based germline genetic testing for men with metastatic prostate cancer","volume":"7","author":"Cheng HH","year":"2023","unstructured":"Cheng HH, Sokolova AO, Gulati R, Internet-based germline genetic testing for men with metastatic prostate cancer. JCO Precis Oncol 2023;7:e2200104."},{"key":"B12","series-title":"N Engl J Med","first-page":"443","article-title":"Inherited DNA-repair gene mutations in men with metastatic prostate cancer","volume":"375","author":"Pritchard CC","year":"2016","unstructured":"Pritchard CC, Mateo J, Walsh MF, Inherited DNA-repair gene mutations in men with metastatic prostate cancer. N Engl J Med 2016;375:443\u2013453."},{"key":"B13","series-title":"JAMA Oncol","first-page":"523","article-title":"Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines","volume":"5","author":"Nicolosi P","year":"2019","unstructured":"Nicolosi P, Ledet E, Yang S, Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines. JAMA Oncol 2019;5:523\u2013528."},{"key":"B14","series-title":"Cancer","first-page":"e70007","article-title":"Prostate cancer incidence and outcomes among Vietnam veterans receiving care in the Veterans Health Administration","volume":"131","author":"Green-Lott AMY","year":"2025","unstructured":"Green-Lott AMY, Wadhwa A, Bailey AV, Prostate cancer incidence and outcomes among Vietnam veterans receiving care in the Veterans Health Administration. Cancer 2025;131:e70007."},{"key":"B15","series-title":"Eur Urol","first-page":"559","article-title":"Association of inherited mutations in DNA repair genes with localized prostate cancer","volume":"81","author":"Lee DJ","year":"2022","unstructured":"Lee DJ, Hausler R, Le AN, Association of inherited mutations in DNA repair genes with localized prostate cancer. Eur Urol 2022;81:559\u2013567."},{"key":"B16","series-title":"Genet Med","first-page":"101246","article-title":"Multi-ethnic heterozygote frequencies of cancer susceptibility genes to inform counseling of reproductive risk","volume":"27","author":"Powers J","year":"2025","unstructured":"Powers J, Wachtel H, Trujillo E, Multi-ethnic heterozygote frequencies of cancer susceptibility genes to inform counseling of reproductive risk. Genet Med 2025;27:101246."},{"key":"B17","series-title":"Nature","first-page":"434","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski KJ","year":"2020","unstructured":"Karczewski KJ, Francioli LC, Tiao G, The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 2020;581:434\u2013443."},{"key":"B18","series-title":"Br J Cancer","first-page":"502","article-title":"Prostate cancer in male BRCA1 and BRCA2 mutation carriers has a more aggressive phenotype","volume":"98","author":"Mitra A","year":"2008","unstructured":"Mitra A, Fisher C, Foster CS, Prostate cancer in male BRCA1 and BRCA2 mutation carriers has a more aggressive phenotype. Br J Cancer 2008;98:502\u2013507."},{"key":"B19","series-title":"J Clin Oncol","first-page":"1748","article-title":"Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer","volume":"31","author":"Castro E","year":"2013","unstructured":"Castro E, Goh C, Olmos D, Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer. J Clin Oncol 2013;31:1748\u20131757."},{"key":"B20","series-title":"Br J Cancer","first-page":"918","article-title":"Prostate cancer in BRCA2 germline mutation carriers is associated with poorer prognosis","volume":"103","author":"Edwards SM","year":"2010","unstructured":"Edwards SM, Evans DGR, Hope Q, Prostate cancer in BRCA2 germline mutation carriers is associated with poorer prognosis. Br J Cancer 2010;103:918\u2013924."},{"key":"B21","series-title":"Am J Hum Genet","first-page":"1","article-title":"Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene","volume":"72","author":"Edwards SM","year":"2003","unstructured":"Edwards SM, Kote-Jarai Z, Meitz J, Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene. 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Cancer Prev Res (Phila) 2011;4:1002\u20131010."},{"key":"B26","series-title":"J Natl Cancer Inst","first-page":"929","article-title":"Prostate cancer progression and survival in BRCA2 mutation carriers","volume":"99","author":"Tryggvadottir L","year":"2007","unstructured":"Tryggvadottir L, Vidarsdottir L, Thorgeirsson T, Prostate cancer progression and survival in BRCA2 mutation carriers. J Natl Cancer Inst 2007;99:929\u2013935."}],"container-title":["Journal of the National Comprehensive Cancer Network"],"original-title":[],"link":[{"URL":"https:\/\/jnccn.org\/view\/journals\/jnccn\/24\/7\/article-e267006.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/jnccn.org\/downloadpdf\/journals\/jnccn\/24\/7\/article-e267006.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/jnccn.org\/downloadpdf\/journals\/jnccn\/24\/7\/article-e267006.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T12:41:43Z","timestamp":1783600903000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnccn.org\/view\/journals\/jnccn\/24\/7\/article-e267006.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":26,"journal-issue":{"issue":"7"},"URL":"https:\/\/doi.org\/10.6004\/jnccn.2026.7006","relation":{},"ISSN":["1540-1405","1540-1413"],"issn-type":[{"value":"1540-1405","type":"print"},{"value":"1540-1413","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]}}}