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

Abstract

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 BRCA1/2 mutations confer an up to 4.5-fold and 8.3-fold increased risk of PC, respectively. BRCA2 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.

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Acknowledgements

RL is supported by the Foundation for Science and Technology, Government of Portugal, SFRH/BD/102232/2014 Individual Doctoral Grant.

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Correspondence to Robert James Hamilton.

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Leão, R.R.N., Price, A.J. & James Hamilton, R. Germline BRCA mutation in male carriers—ripe for precision oncology?. Prostate Cancer Prostatic Dis 21, 48–56 (2018). https://doi.org/10.1038/s41391-017-0018-5

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