Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness
Patel, Vivek L. ; Borg, Åke LU ; Ehrencrona, Hans LU
and Rebbeck, Timothy R.
(2020)
In Cancer Research
80(3).
p.624-638
- 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).... (More)
- 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. ©2019 American Association for Cancer Research. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/81820646-aef0-4cc4-86fb-c2f21c4e4992
- author
- Patel, Vivek L.
; Borg, Åke
LU
; Ehrencrona, Hans
LU
and Rebbeck, Timothy R.
- author collaboration
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cancer Research
- volume
- 80
- issue
- 3
- pages
- 15 pages
- publisher
- American Association for Cancer Research Inc.
- external identifiers
-
- scopus:85079022145
- pmid:31723001
- ISSN
- 1538-7445
- DOI
- 10.1158/0008-5472.CAN-19-1840
- language
- English
- LU publication?
- yes
- id
- 81820646-aef0-4cc4-86fb-c2f21c4e4992
- date added to LUP
- 2020-02-19 13:08:21
- date last changed
- 2022-04-18 20:36:53
@article{81820646-aef0-4cc4-86fb-c2f21c4e4992,
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. ©2019 American Association for Cancer Research.}},
author = {{Patel, Vivek L. and Borg, Åke and Ehrencrona, Hans and Rebbeck, Timothy R.}},
issn = {{1538-7445}},
language = {{eng}},
number = {{3}},
pages = {{624--638}},
publisher = {{American Association for Cancer Research Inc.}},
series = {{Cancer Research}},
title = {{Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness}},
url = {{http://dx.doi.org/10.1158/0008-5472.CAN-19-1840}},
doi = {{10.1158/0008-5472.CAN-19-1840}},
volume = {{80}},
year = {{2020}},
}