Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

Daniel R Barnes; Valentina Silvestri; Goska Leslie; Lesley McGuffog; Joe Dennis; Xin Yang; Julian Adlard; Bjarni A Agnarsson; Munaza Ahmed; Kristiina Aittomäki; Irene L Andrulis; Adalgeir Arason; Norbert Arnold; Bernd Auber; Jacopo Azzollini; Judith Balmaña; Rosa B Barkardottir; Daniel Barrowdale; Julian Barwell; Muriel Belotti; Javier Benitez; Pascaline Berthet; Susanne E Boonen; Åke Borg; Aniko Bozsik; Angela F Brady; Paul Brennan; Carole Brewer; Joan Brunet; Agostino Bucalo; Saundra S Buys; Trinidad Caldés; Maria A Caligo; Ian Campbell; Hayley Cassingham; Lise Lotte Christensen; Giulia Cini; Kathleen B M Claes; Jackie Cook; Anna Coppa; Laura Cortesi; Giuseppe Damante; Esther Darder; Rosemarie Davidson; Miguel de la Hoya; Thomas V O Hansen; Judit Horvath; Uffe Birk Jensen; Charlotte Lautrup; Inge Sokilde Pedersen; GEMO Study Collaborators

doi:10.1093/jnci/djab147

Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

Daniel R Barnes, Valentina Silvestri, Goska Leslie, Lesley McGuffog, Joe Dennis, Xin Yang, Julian Adlard, Bjarni A Agnarsson, Munaza Ahmed, Kristiina Aittomäki, Irene L Andrulis, Adalgeir Arason, Norbert Arnold, Bernd Auber, Jacopo Azzollini, Judith Balmaña, Rosa B Barkardottir, Daniel Barrowdale, Julian Barwell, Muriel BelottiJavier Benitez, Pascaline Berthet, Susanne E Boonen, Åke Borg, Aniko Bozsik, Angela F Brady, Paul Brennan, Carole Brewer, Joan Brunet, Agostino Bucalo, Saundra S Buys, Trinidad Caldés, Maria A Caligo, Ian Campbell, Hayley Cassingham, Lise Lotte Christensen, Giulia Cini, Kathleen B M Claes, Jackie Cook, Anna Coppa, Laura Cortesi, Giuseppe Damante, Esther Darder, Rosemarie Davidson, Miguel de la Hoya, Thomas V O Hansen, Judit Horvath, Uffe Birk Jensen, Charlotte Lautrup, Inge Sokilde Pedersen, GEMO Study Collaborators

Institut for Klinisk Medicin - Klinisk Genetisk afdeling

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

27 Citationer (Scopus)

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Abstract

BACKGROUND: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers.

METHODS: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk.

RESULTS: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions.

CONCLUSIONS: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.

Originalsprog	Engelsk
Artikelnummer	147
Tidsskrift	Journal of the National Cancer Institute
Vol/bind	114
Nummer	1
Sider (fra-til)	109-122
Antal sider	14
ISSN	0027-8874
DOI	https://doi.org/10.1093/jnci/djab147
Status	Udgivet - jan. 2022

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10.1093/jnci/djab147Licens: CC BY

djab147Forlagets udgivne version, 6,24 MBLicens: CC BY

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Barnes, D. R., Silvestri, V., Leslie, G., McGuffog, L., Dennis, J., Yang, X., Adlard, J., Agnarsson, B. A., Ahmed, M., Aittomäki, K., Andrulis, I. L., Arason, A., Arnold, N., Auber, B., Azzollini, J., Balmaña, J., Barkardottir, R. B., Barrowdale, D., Barwell, J., ... GEMO Study Collaborators (2022). Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores. Journal of the National Cancer Institute, 114(1), 109-122. Artikel 147. https://doi.org/10.1093/jnci/djab147

@article{5d850d2e74f842feb9c2935f43719259,

title = "Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores",

abstract = "BACKGROUND: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers.METHODS: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk.RESULTS: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions.CONCLUSIONS: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.",

keywords = "ASSOCIATION, MUTATION CARRIERS, OVARIAN",

author = "Barnes, {Daniel R} and Valentina Silvestri and Goska Leslie and Lesley McGuffog and Joe Dennis and Xin Yang and Julian Adlard and Agnarsson, {Bjarni A} and Munaza Ahmed and Kristiina Aittom{\"a}ki and Andrulis, {Irene L} and Adalgeir Arason and Norbert Arnold and Bernd Auber and Jacopo Azzollini and Judith Balma{\~n}a and Barkardottir, {Rosa B} and Daniel Barrowdale and Julian Barwell and Muriel Belotti and Javier Benitez and Pascaline Berthet and Boonen, {Susanne E} and {\AA}ke Borg and Aniko Bozsik and Brady, {Angela F} and Paul Brennan and Carole Brewer and Joan Brunet and Agostino Bucalo and Buys, {Saundra S} and Trinidad Cald{\'e}s and Caligo, {Maria A} and Ian Campbell and Hayley Cassingham and Christensen, {Lise Lotte} and Giulia Cini and Claes, {Kathleen B M} and Jackie Cook and Anna Coppa and Laura Cortesi and Giuseppe Damante and Esther Darder and Rosemarie Davidson and {de la Hoya}, Miguel and Hansen, {Thomas V O} and Judit Horvath and Jensen, {Uffe Birk} and Charlotte Lautrup and Pedersen, {Inge Sokilde} and {GEMO Study Collaborators}",

year = "2022",

month = jan,

doi = "10.1093/jnci/djab147",

language = "English",

volume = "114",

pages = "109--122",

journal = "Journal of the National Cancer Institute",

issn = "0027-8874",

publisher = "Oxford University Press",

number = "1",

}

Barnes, DR, Silvestri, V, Leslie, G, McGuffog, L, Dennis, J, Yang, X, Adlard, J, Agnarsson, BA, Ahmed, M, Aittomäki, K, Andrulis, IL, Arason, A, Arnold, N, Auber, B, Azzollini, J, Balmaña, J, Barkardottir, RB, Barrowdale, D, Barwell, J, Belotti, M, Benitez, J, Berthet, P, Boonen, SE, Borg, Å, Bozsik, A, Brady, AF, Brennan, P, Brewer, C, Brunet, J, Bucalo, A, Buys, SS, Caldés, T, Caligo, MA, Campbell, I, Cassingham, H, Christensen, LL, Cini, G, Claes, KBM, Cook, J, Coppa, A, Cortesi, L, Damante, G, Darder, E, Davidson, R, de la Hoya, M, Hansen, TVO, Horvath, J, Jensen, UB , Lautrup, C, Pedersen, IS & GEMO Study Collaborators 2022, 'Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores', Journal of the National Cancer Institute, bind 114, nr. 1, 147, s. 109-122. https://doi.org/10.1093/jnci/djab147

Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores. / Barnes, Daniel R; Silvestri, Valentina; Leslie, Goska et al.
I: Journal of the National Cancer Institute, Bind 114, Nr. 1, 147, 01.2022, s. 109-122.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

AU - Barnes, Daniel R

AU - Silvestri, Valentina

AU - Leslie, Goska

AU - McGuffog, Lesley

AU - Dennis, Joe

AU - Yang, Xin

AU - Adlard, Julian

AU - Agnarsson, Bjarni A

AU - Ahmed, Munaza

AU - Aittomäki, Kristiina

AU - Andrulis, Irene L

AU - Arason, Adalgeir

AU - Arnold, Norbert

AU - Auber, Bernd

AU - Azzollini, Jacopo

AU - Balmaña, Judith

AU - Barkardottir, Rosa B

AU - Barrowdale, Daniel

AU - Barwell, Julian

AU - Belotti, Muriel

AU - Benitez, Javier

AU - Berthet, Pascaline

AU - Boonen, Susanne E

AU - Borg, Åke

AU - Bozsik, Aniko

AU - Brady, Angela F

AU - Brennan, Paul

AU - Brewer, Carole

AU - Brunet, Joan

AU - Bucalo, Agostino

AU - Buys, Saundra S

AU - Caldés, Trinidad

AU - Caligo, Maria A

AU - Campbell, Ian

AU - Cassingham, Hayley

AU - Christensen, Lise Lotte

AU - Cini, Giulia

AU - Claes, Kathleen B M

AU - Cook, Jackie

AU - Coppa, Anna

AU - Cortesi, Laura

AU - Damante, Giuseppe

AU - Darder, Esther

AU - Davidson, Rosemarie

AU - de la Hoya, Miguel

AU - Hansen, Thomas V O

AU - Horvath, Judit

AU - Jensen, Uffe Birk

AU - Lautrup, Charlotte

AU - Pedersen, Inge Sokilde

AU - GEMO Study Collaborators

PY - 2022/1

Y1 - 2022/1

N2 - BACKGROUND: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers.METHODS: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk.RESULTS: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions.CONCLUSIONS: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.

AB - BACKGROUND: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers.METHODS: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk.RESULTS: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions.CONCLUSIONS: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.

KW - ASSOCIATION

KW - MUTATION CARRIERS

KW - OVARIAN

UR - http://www.scopus.com/inward/record.url?scp=85122613384&partnerID=8YFLogxK

U2 - 10.1093/jnci/djab147

DO - 10.1093/jnci/djab147

M3 - Journal article

C2 - 34320204

SN - 0027-8874

VL - 114

SP - 109

EP - 122

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

IS - 1

M1 - 147

ER -

Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

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