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Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Patel, Vivek L 
Busch, Evan L 
Friebel, Tara M 
Cronin, Angel 

Abstract

Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 3' region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001-c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25-2.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63-5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71-4.68; P = 0.00004) and elevated risk of Gleason 8+ prostate cancer (HR = 4.95; 95% CI, 2.12-11.54; P = 0.0002). No genotype-phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. SIGNIFICANCE: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.

Description

Keywords

Adolescent, Adult, Aged, Aged, 80 and over, BRCA1 Protein, BRCA2 Protein, Genetic Association Studies, Genetic Predisposition to Disease, Genomics, Heterozygote, Humans, Male, Middle Aged, Mutation, Prognosis, Prostatic Neoplasms, Risk Factors, Young Adult

Journal Title

Cancer Res

Conference Name

Journal ISSN

0008-5472
1538-7445

Volume Title

80

Publisher

American Association for Cancer Research (AACR)

Rights

All rights reserved
Sponsorship
Cancer Research UK (20861)
National Cancer Institute (U19CA148537)
National Cancer Institute (U19CA148065)
Cancer Research UK (12014)
National Cancer Institute (R01CA128978)
Wellcome Trust (203477/Z/16/Z)
European Commission (223175)
Cancer Research UK (23382)
Cancer Research UK (10118)
Cancer Research Uk (None)
Cancer Research UK (16565)