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

HEBON Investigators; Vivek L Patel; Evan L Busch; Tara M Friebel; Angel Cronin; Goska Leslie; Lesley McGuffog; Julian Adlard; Simona Agata; Bjarni A Agnarsson; Munaza Ahmed; Kristiina Aittomäki; Elisa Alducci; Irene L Andrulis; Adalgeir Arason; Norbert Arnold; Grazia Artioli; Brita Arver; Bernd Auber; Jacopo Azzollini; Judith Balmaña; Rosa B Barkardottir; Daniel R Barnes; Alicia Barroso; Daniel Barrowdale; Muriel Belotti; Javier Benitez; Birgitte Bertelsen; Marinus J Blok; Istvan Bodrogi; Valérie Bonadona; Bernardo Bonanni; Davide Bondavalli; Susanne E Boonen; Julika Borde; Ake Borg; Angela R Bradbury; Angela Brady; Carole Brewer; Joan Brunet; Bruno Buecher; Saundra S Buys; Santiago Cabezas-Camarero; Trinidad Caldés; Almuth Caliebe; Maria A Caligo; Mariarosaria Calvello; Ian G Campbell; Ileana Carnevali; Estela Carrasco; Mary B Daly

doi:10.1158/0008-5472.CAN-19-1840

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

HEBON Investigators, Vivek L Patel, Evan L Busch, Tara M Friebel, Angel Cronin, Goska Leslie, Lesley McGuffog, Julian Adlard, Simona Agata, Bjarni A Agnarsson, Munaza Ahmed, Kristiina Aittomäki, Elisa Alducci, Irene L Andrulis, Adalgeir Arason, Norbert Arnold, Grazia Artioli, Brita Arver, Bernd Auber, Jacopo AzzolliniJudith Balmaña, Rosa B Barkardottir, Daniel R Barnes, Alicia Barroso, Daniel Barrowdale, Muriel Belotti, Javier Benitez, Birgitte Bertelsen, Marinus J Blok, Istvan Bodrogi, Valérie Bonadona, Bernardo Bonanni, Davide Bondavalli, Susanne E Boonen, Julika Borde, Ake Borg, Angela R Bradbury, Angela Brady, Carole Brewer, Joan Brunet, Bruno Buecher, Saundra S Buys, Santiago Cabezas-Camarero, Trinidad Caldés, Almuth Caliebe, Maria A Caligo, Mariarosaria Calvello, Ian G Campbell, Ileana Carnevali, Estela Carrasco, Mary B Daly

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

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.

Original language	English
Pages (from-to)	624-638
Number of pages	15
Journal	Cancer Research
Volume	80
Issue number	3
DOIs	https://doi.org/10.1158/0008-5472.CAN-19-1840
State	Published - Jan 1 2020

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1158/0008-5472.CAN-19-1840

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HEBON Investigators, Patel, V. L., Busch, E. L., Friebel, T. M., Cronin, A., Leslie, G., McGuffog, L., Adlard, J., Agata, S., Agnarsson, B. A., Ahmed, M., Aittomäki, K., Alducci, E., Andrulis, I. L., Arason, A., Arnold, N., Artioli, G., Arver, B., Auber, B., ... Daly, M. B. (2020). Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness. Cancer Research, 80(3), 624-638. https://doi.org/10.1158/0008-5472.CAN-19-1840

@article{19b27b052b494bbdb2d025977d64e951,

title = "Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness",

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.",

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

author = "{HEBON Investigators} and Patel, {Vivek L} and Busch, {Evan L} and Friebel, {Tara M} and Angel Cronin and Goska Leslie and Lesley McGuffog and Julian Adlard and Simona Agata and Agnarsson, {Bjarni A} and Munaza Ahmed and Kristiina Aittom{\"a}ki and Elisa Alducci and Andrulis, {Irene L} and Adalgeir Arason and Norbert Arnold and Grazia Artioli and Brita Arver and Bernd Auber and Jacopo Azzollini and Judith Balma{\~n}a and Barkardottir, {Rosa B} and Barnes, {Daniel R} and Alicia Barroso and Daniel Barrowdale and Muriel Belotti and Javier Benitez and Birgitte Bertelsen and Blok, {Marinus J} and Istvan Bodrogi and Val{\'e}rie Bonadona and Bernardo Bonanni and Davide Bondavalli and Boonen, {Susanne E} and Julika Borde and Ake Borg and Bradbury, {Angela R} and Angela Brady and Carole Brewer and Joan Brunet and Bruno Buecher and Buys, {Saundra S} and Santiago Cabezas-Camarero and Trinidad Cald{\'e}s and Almuth Caliebe and Caligo, {Maria A} and Mariarosaria Calvello and Campbell, {Ian G} and Ileana Carnevali and Estela Carrasco and Daly, {Mary B}",

note = "{\textcopyright}2019 American Association for Cancer Research.",

year = "2020",

month = jan,

day = "1",

doi = "10.1158/0008-5472.CAN-19-1840",

language = "English",

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pages = "624--638",

journal = "Cancer Research",

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HEBON Investigators, Patel, VL, Busch, EL, Friebel, TM, Cronin, A, Leslie, G, McGuffog, L, Adlard, J, Agata, S, Agnarsson, BA, Ahmed, M, Aittomäki, K, Alducci, E, Andrulis, IL, Arason, A, Arnold, N, Artioli, G, Arver, B, Auber, B, Azzollini, J, Balmaña, J, Barkardottir, RB, Barnes, DR, Barroso, A, Barrowdale, D, Belotti, M, Benitez, J, Bertelsen, B, Blok, MJ, Bodrogi, I, Bonadona, V, Bonanni, B, Bondavalli, D, Boonen, SE, Borde, J, Borg, A, Bradbury, AR, Brady, A, Brewer, C, Brunet, J, Buecher, B, Buys, SS, Cabezas-Camarero, S, Caldés, T, Caliebe, A, Caligo, MA, Calvello, M, Campbell, IG, Carnevali, I, Carrasco, E & Daly, MB 2020, 'Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness', Cancer Research, vol. 80, no. 3, pp. 624-638. https://doi.org/10.1158/0008-5472.CAN-19-1840

TY - JOUR

T1 - Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness

AU - HEBON Investigators

AU - Patel, Vivek L

AU - Busch, Evan L

AU - Friebel, Tara M

AU - Cronin, Angel

AU - Leslie, Goska

AU - McGuffog, Lesley

AU - Adlard, Julian

AU - Agata, Simona

AU - Agnarsson, Bjarni A

AU - Ahmed, Munaza

AU - Aittomäki, Kristiina

AU - Alducci, Elisa

AU - Andrulis, Irene L

AU - Arason, Adalgeir

AU - Arnold, Norbert

AU - Artioli, Grazia

AU - Arver, Brita

AU - Auber, Bernd

AU - Azzollini, Jacopo

AU - Balmaña, Judith

AU - Barkardottir, Rosa B

AU - Barnes, Daniel R

AU - Barroso, Alicia

AU - Barrowdale, Daniel

AU - Belotti, Muriel

AU - Benitez, Javier

AU - Bertelsen, Birgitte

AU - Blok, Marinus J

AU - Bodrogi, Istvan

AU - Bonadona, Valérie

AU - Bonanni, Bernardo

AU - Bondavalli, Davide

AU - Boonen, Susanne E

AU - Borde, Julika

AU - Borg, Ake

AU - Bradbury, Angela R

AU - Brady, Angela

AU - Brewer, Carole

AU - Brunet, Joan

AU - Buecher, Bruno

AU - Buys, Saundra S

AU - Cabezas-Camarero, Santiago

AU - Caldés, Trinidad

AU - Caliebe, Almuth

AU - Caligo, Maria A

AU - Calvello, Mariarosaria

AU - Campbell, Ian G

AU - Carnevali, Ileana

AU - Carrasco, Estela

AU - Daly, Mary B

PY - 2020/1/1

Y1 - 2020/1/1

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - BRCA1 Protein/genetics

KW - BRCA2 Protein/genetics

KW - Genetic Association Studies

KW - Genetic Predisposition to Disease

KW - Genomics/methods

KW - Heterozygote

KW - Humans

KW - Male

KW - Middle Aged

KW - Mutation

KW - Prognosis

KW - Prostatic Neoplasms/genetics

KW - Risk Factors

KW - Young Adult

UR - http://www.scopus.com/inward/record.url?scp=85079022145&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-19-1840

DO - 10.1158/0008-5472.CAN-19-1840

M3 - Article

C2 - 31723001

SN - 0008-5472

VL - 80

SP - 624

EP - 638

JO - Cancer Research

JF - Cancer Research

IS - 3

ER -

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

Abstract

Keywords

UN SDGs

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