{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:06:03Z","timestamp":1785434763435,"version":"3.56.0"},"reference-count":32,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2017,6,28]],"date-time":"2017-06-28T00:00:00Z","timestamp":1498608000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"University of Michigan Prostate Cancer Specialized Program of Research Excellence (SPORE)","award":["P50 CA186786"],"award-info":[{"award-number":["P50 CA186786"]}]},{"name":"University of Michigan Comprehensive Cancer Center Sequencing Core"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2017,10,15]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Prostate cancer has a significant heritable component, and rare deleterious germline variants in certain genes can increase the risk of the disease. The aim of the current study was to describe the prevalence of pathogenic germline variants in cancer\u2010predisposing genes in men with prostate cancer and at least 1 additional primary cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Using a multigene panel, the authors sequenced germline DNA from 102 men with prostate cancer and at least 1 additional primary cancer who also met \u22651 of the following criteria: 1) age \u226455 years at the time of diagnosis of the first malignancy; 2) rare tumor type or atypical presentation of a common tumor; and\/or 3) \u22653 primary malignancies. Cancer family history and clinicopathologic data were independently reviewed by a clinical genetic counselor to determine whether the patient met established criteria for testing for a hereditary cancer syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Sequencing identified approximately 3500 variants. Nine protein\u2010truncating deleterious mutations were found across 6 genes, including <jats:italic>BRCA2<\/jats:italic>, ataxia telangiectasia mutated (<jats:italic>ATM<\/jats:italic>), mutL homolog 1 (<jats:italic>MLH1<\/jats:italic>), BRCA1 interacting protein C\u2010terminal helicase 1 (<jats:italic>BRIP1<\/jats:italic>), partner and localizer of BRCA2 (<jats:italic>PALB2<\/jats:italic>), and fibroblast growth factor receptor 3 (<jats:italic>FGFR3<\/jats:italic>). Likely pathogenic missense variants were identified in checkpoint kinase 2 (<jats:italic>CHEK2<\/jats:italic>) and homeobox protein Hox\u2010B13 (<jats:italic>HOXB13<\/jats:italic>). In total, 11 of 102 patients (10.8%) were found to have pathogenic or likely pathogenic mutations in cancer\u2010predisposing genes. The majority of these men (64%) did not meet current clinical criteria for germline testing.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Men with prostate cancer and at least 1 additional primary cancer are enriched for harboring a germline deleterious mutation in a cancer\u2010predisposing gene that may impact cancer prognosis and treatment, but the majority do not meet current criteria for clinical genetic testing. <jats:bold><jats:italic>Cancer<\/jats:italic> 2017;123:3925\u201032<\/jats:bold>. \u00a9 <jats:italic>2017 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.30817","type":"journal-article","created":{"date-parts":[[2017,6,28]],"date-time":"2017-06-28T10:03:16Z","timestamp":1498644196000},"page":"3925-3932","source":"Crossref","is-referenced-by-count":54,"title":["Germline genetic variants in men with prostate cancer and one or more additional cancers"],"prefix":"10.1002","volume":"123","author":[{"given":"Patrick G.","family":"Pili\u00e9","sequence":"first","affiliation":[{"name":"Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Michigan Medical School Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen L.","family":"Hanson","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Michigan Medical School Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan E.","family":"Dayno","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Michigan Medical School Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley 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