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Prostate Cancer Risk by BRCA2 Genomic Regions.

Nyberg, T; Frost, D; Barrowdale, D; Evans, DG; Bancroft, E; Adlard, J; Ahmed, M; Barwell, J; Brady, AF; Brewer, C; et al. Nyberg, T; Frost, D; Barrowdale, D; Evans, DG; Bancroft, E; Adlard, J; Ahmed, M; Barwell, J; Brady, AF; Brewer, C; Cook, J; Davidson, R; Donaldson, A; Eason, J; Gregory, H; Henderson, A; Izatt, L; Kennedy, MJ; Miller, C; Morrison, PJ; Murray, A; Ong, K-R; Porteous, M; Pottinger, C; Rogers, MT; Side, L; Snape, K; Tripathi, V; Walker, L; Tischkowitz, M; Eeles, R; Easton, DF; Antoniou, AC (2020) Prostate Cancer Risk by BRCA2 Genomic Regions. Eur Urol, 78 (4). pp. 494-497. ISSN 1873-7560 https://doi.org/10.1016/j.eururo.2020.05.005
SGUL Authors: Snape, Katie Mairwen Greenwood

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Abstract

A BRCA2 prostate cancer cluster region (PCCR) was recently proposed (c.7914 to 3') wherein pathogenic variants (PVs) are associated with higher prostate cancer (PCa) risk than PVs elsewhere in the BRCA2 gene. Using a prospective cohort study of 447 male BRCA2 PV carriers recruited in the UK and Ireland from 1998 to 2016, we estimated standardised incidence ratios (SIRs) compared with population incidences and assessed variation in risk by PV location. Carriers of PVs in the PCCR had a PCa SIR of 8.33 (95% confidence interval [CI] 4.46-15.6) and were at a higher risk of PCa than carriers of other BRCA2 PVs (SIR = 3.31, 95% CI 1.97-5.57; hazard ratio = 2.34, 95% CI 1.09-5.03). PCCR PV carriers had an estimated cumulative PCa risk of 44% (95% CI 23-72%) by the age of 75 yr and 78% (95% CI 54-94%) by the age of 85 yr. Our results corroborate the existence of a PCCR in BRCA2 in a prospective cohort. PATIENT SUMMARY: In this report, we investigated whether the risk of prostate cancer for men with a harmful mutation in the BRCA2 gene differs based on where in the gene the mutation is located. We found that men with mutations in one region of BRCA2 had a higher risk of prostate cancer than men with mutations elsewhere in the gene.

Item Type: Article
Additional Information: © 2020 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: BRCA2, Genetic risk, Genomic region, Prospective cohort study, Prostate cancer, Prostate cancer cluster region, 1103 Clinical Sciences, Urology & Nephrology
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Journal or Publication Title: Eur Urol
ISSN: 1873-7560
Language: eng
Dates:
DateEvent
October 2020Published
10 June 2020Published Online
5 May 2020Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
C12292/A20861Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
C12292/A22820Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
C1287/A23382Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
C1287/A26886Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
IS-BRC-1215-20007National Institute for Health Researchhttp://dx.doi.org/10.13039/501100000272
C5047/A8385Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
PubMed ID: 32532514
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/112104
Publisher's version: https://doi.org/10.1016/j.eururo.2020.05.005

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