Germline mutations in penetrant cancer predisposition genes are rare in men with prostate cancer selecting active surveillance
Autor: | Lauren Brady, Lisa F. Newcomb, Kehao Zhu, Yingye Zheng, Hilary Boyer, Navonil De Sarkar, Jesse K. McKenney, James D. Brooks, Peter R. Carroll, Atreya Dash, William J. Ellis, Christopher P. Filson, Martin E. Gleave, Michael A. Liss, Frances Martin, Todd M. Morgan, Ian M. Thompson, Andrew A. Wagner, Colin C. Pritchard, Daniel W. Lin, Peter S. Nelson |
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Rok vydání: | 2022 |
Předmět: |
Urologic Diseases
Male Cancer Research Oncology and Carcinogenesis Genes BRCA2 Genetics 2.1 Biological and endogenous factors Humans Genetic Predisposition to Disease Radiology Nuclear Medicine and imaging Aetiology Watchful Waiting adverse pathology Germ-Line Mutation Cancer Retrospective Studies Prevention Prostate Cancer active surveillance Prostatic Neoplasms BRCA2 Good Health and Well Being Genes Oncology germline mutations Biochemistry and Cell Biology |
Zdroj: | Cancer medicine, vol 11, iss 22 |
ISSN: | 2045-7634 |
Popis: | BackgroundPathogenic germline mutations in several rare penetrant cancer predisposition genes are associated with an increased risk of aggressive prostate cancer (PC). Our objectives were to determine the prevalence of pathogenic germline mutations in men with low-risk PC on active surveillance, and assess whether pathogenic germline mutations associate with grade reclassification or adverse pathology, recurrence, or metastases, in men treated after initial surveillance.MethodsMen prospectively enrolled in the Canary Prostate Active Surveillance Study (PASS) were retrospectively sampled for the study. Germline DNA was sequenced utilizing a hereditary cancer gene panel. Mutations were classified according to the American College of Clinical Genetics and Genomics' guidelines. The association of pathogenic germline mutations with grade reclassification and adverse characteristics was evaluated by weighted Cox proportional hazards modeling and conditional logistic regression, respectively.ResultsOverall, 29 of 437 (6.6%) study participants harbored a pathogenic germline mutation of which 19 occurred in a gene involved in DNA repair (4.3%). Eight participants (1.8%) had pathogenic germline mutations in three genes associated with aggressive PC: ATM, BRCA1, and BRCA2. The presence of pathogenic germline mutations in DNA repair genes did not associate with adverse characteristics (univariate analysis HR=0.87, 95% CI: 0.36-2.06, p=0.7). The carrier rates of pathogenic germline mutations in ATM, BRCA1, and BRCA2did not differ in men with or without grade reclassification (1.9% vs. 1.8%).ConclusionThe frequency of pathogenic germline mutations in penetrant cancer predisposition genes is extremely low in men with PC undergoing active surveillance and pathogenic germline mutations had no apparent association with grade reclassification or adverse characteristics. |
Databáze: | OpenAIRE |
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