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Association of genomic domains in BRCA1 and BRCA2 with prostate cancer risk and aggressiveness

Association of genomic domains in BRCA1 and BRCA2 with prostate cancer risk and aggressiveness
Association of genomic domains in BRCA1 and BRCA2 with prostate cancer risk and aggressiveness
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.
0008-5472
624-638
Rebbeck, Timothy
83f40ba3-8fb1-4ab0-b1aa-71abe8109334
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Patel, Vivek
f2701597-6144-41a5-8564-5506c412c803
Busch, Evan L.
e25f82bd-4988-4e03-9a6a-c4be4980d1a4
Friebel, Tara M.
2f78bec5-da21-4de3-a005-5f2cc090843f
HEBON Investigators
Rebbeck, Timothy
83f40ba3-8fb1-4ab0-b1aa-71abe8109334
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Patel, Vivek
f2701597-6144-41a5-8564-5506c412c803
Busch, Evan L.
e25f82bd-4988-4e03-9a6a-c4be4980d1a4
Friebel, Tara M.
2f78bec5-da21-4de3-a005-5f2cc090843f

Patel, Vivek, Busch, Evan L. and Friebel, Tara M. , HEBON Investigators (2020) Association of genomic domains in BRCA1 and BRCA2 with prostate cancer risk and aggressiveness. Cancer Research, 80 (3), 624-638.

Record type: Article

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.

Text
Rebbeck PCCR CR Revised 8.5.2019 CLEAN
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More information

Accepted/In Press date: 19 September 2019
e-pub ahead of print date: 13 November 2019
Published date: 1 February 2020

Identifiers

Local EPrints ID: 438074
URI: http://eprints.soton.ac.uk/id/eprint/438074
ISSN: 0008-5472
PURE UUID: 304fb6cb-152b-47e2-864f-c52f17f5165d
ORCID for Diana Eccles: ORCID iD orcid.org/0000-0002-9935-3169

Catalogue record

Date deposited: 27 Feb 2020 17:31
Last modified: 26 Nov 2021 05:34

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Contributors

Author: Timothy Rebbeck
Author: Diana Eccles ORCID iD
Author: Vivek Patel
Author: Evan L. Busch
Author: Tara M. Friebel
Corporate Author: HEBON Investigators

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