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

Leão, Ricardo Romão Nazário and Price, Aryeh Joshua and Hamilton, Robert James (2017) Germline BRCA mutation in male carriers—ripe for precision oncology? Prostate Cancer and Prostatic Diseases, 21 . pp. 48-56. ISSN 1365-7852. https://resolver.caltech.edu/CaltechAUTHORS:20171218-071343524

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/s41391-017-0018-5DOIArticle
https://www.nature.com/articles/s41391-017-0018-5PublisherArticle
ORCID:
AuthorORCID
Leão, Ricardo Romão Nazário0000-0003-3719-717X
Additional Information:© 2017 Nature Publishing Group. Received: 06 July 2017; Accepted: 20 August 2017; Published online: 14 December 2017. RL is supported by the Foundation for Science and Technology, Government of Portugal, SFRH/BD/102232/2014 Individual Doctoral Grant. The authors declare that they have no conflict of interest.
Funders:
Funding AgencyGrant Number
Fundação para a Ciência e a Tecnologia (FCT)SFRH/BD/102232/2014
Record Number:CaltechAUTHORS:20171218-071343524
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20171218-071343524
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:83947
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:18 Dec 2017 17:55
Last Modified:03 Oct 2019 19:12

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