Germline BRCA mutation in male carriers—ripe for precision oncology?

• Published in: Prostate cancer and prostatic diseases 2018-04, Vol.21 (1), p.48-56
• Main Authors: Leão, Ricardo Romão Nazário, Price, Aryeh Joshua, James Hamilton, Robert
• Format: Article
• Language: English
• Subjects: 631/67/68; 692/308/575; Biomedical and Life Sciences; Biomedicine; BRCA mutations; BRCA1 protein; BRCA1 Protein - genetics; BRCA2 protein; BRCA2 Protein - genetics; Breast cancer; Cancer; Cancer metastasis; Cancer prevention; Cancer Research; Castration; Chemotherapy; Deoxyribonucleic acid; Development and progression; DNA; DNA repair; Early Detection of Cancer; Gene mutation; Genes; Genetic aspects; Genetic diversity; Genetic factors; Genetic Predisposition to Disease; Genetics; Germ-Line Mutation - genetics; Health risk assessment; Health risks; Humans; Maintenance; Male; Mediation; Medical prognosis; Metastases; Mutation; Online searching; Precision Medicine; Prognosis; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Review Article; Risk; Risk groups; Screening; Subgroups; Tumor suppressor genes; Tumors
• ISSN: 1365-7852; 1476-5608
• DOI: 10.1038/s41391-017-0018-5

Background Prostate cancer (PC) is one of the known heritable cancers with individual variations attributed to genetic factors. BRCA1 and BRCA2 are tumour suppressor genes with crucial roles in repairing DNA and thereby maintaining genomic integrity. Germline BRCA mutations predispose to multiple familial tumour types including PC. Methods We performed a Pubmed database search along with review of reference lists from prominent articles to capture papers exploring the association between BRCA mtuations and prostate cancer risk and prognosis. Articles were retrieved until May 2017 and filtered for relevance, and publication type. Results We explored familial PC genetics; discussed the discovery and magnitude of the association between BRCA mutations and PC risk and outcome; examined implications of factoring BRCA mutations into PC screening; and discussed the rationale for chemoprevention in this high-risk population. We confirmed that BRCA 1/2 mutations confer an up to 4.5-fold and 8.3-fold increased risk of PC, respectively. BRCA 2 mutations are associated with an increased risk of high-grade disease, progression to metastatic castration-resistant disease, and 5-year cancer-specific survival rates of 50 to 60%. Conclusion Despite the growing body of research on DNA repair genes, deeper analysis is needed to understand the aetiological role of germline BRCA mutations in the natural history of PC. There is a need for awareness to screen for this marker of PC risk. There is similarly an opportunity for structured PC screening programs for BRCA mutation carriers. Finally, further research is required to identify potential chemopreventive strategies for this high-risk subgroup.