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; Kim De Leeneer; Robin de Putter; Jesús Del Valle; Orland Diez; Yuan Chun Ding; Susan M Domchek; Alan Donaldson; Jacqueline Eason; Ros Eeles; Christoph Engel; D Gareth Evans; Lidia Feliubadaló; Florentia Fostira; Megan Frone; Debra Frost; David Gallagher; Andrea Gehrig; Sophie Giraud; Gord Glendon; Andrew K Godwin; David E Goldgar; Mark H Greene; Helen Gregory; Eva Gross; Eric Hahnen; Ute Hamann; Thomas V O Hansen; Helen Hanson; Julia Hentschel; Judit Horvath; Louise Izatt; Angel Izquierdo; Paul A James; Ramunas Janavicius; Uffe Birk Jensen; Oskar Th Johannsson; Esther M John; Gero Kramer; Lone Kroeldrup; Torben A Kruse; Charlotte Lautrup; Conxi Lazaro; Fabienne Lesueur; Adria Lopez-Fernández; Phuong L Mai; Siranoush Manoukian; Zoltan Matrai; Laura Matricardi; Kara N Maxwell; Noura Mebirouk; Alfons Meindl; Marco Montagna; Alvaro N Monteiro; Patrick J Morrison; Taru A Muranen; Alex Murray; Katherine L Nathanson; Susan L Neuhausen; Heli Nevanlinna; Tu Nguyen-Dumont; Dieter Niederacher; Edith Olah; Olufunmilayo I Olopade; Domenico Palli; Michael T Parsons; Inge Sokilde Pedersen; Bernard Peissel; Pedro Perez-Segura; Paolo Peterlongo; Annabeth H Petersen; Pedro Pinto; Mary E Porteous; Caroline Pottinger; Miquel Angel Pujana; Paolo Radice; Juliane Ramser; Johanna Rantala; Mark Robson; Mark T Rogers; Karina Rønlund; Andreas Rump; Ana María Sánchez de Abajo; Payal D Shah; Saba Sharif; Lucy E Side; Christian F Singer; Zsofia Stadler; Linda Steele; Dominique Stoppa-Lyonnet; Christian Sutter; Yen Yen Tan; Manuel R Teixeira; Alex Teulé; Darcy L Thull; Marc Tischkowitz; Amanda E Toland; Stefania Tommasi; Angela Toss; Alison H Trainer; Vishakha Tripathi; Virginia Valentini; Christi J van Asperen; Marta Venturelli; Alessandra Viel; Joseph Vijai; Lisa Walker; Shan Wang-Gohrke; Barbara Wappenschmidt; Anna Whaite; Ines Zanna; Kenneth Offit; Mads Thomassen; Fergus J Couch; Rita K Schmutzler; Jacques Simard; Douglas F Easton; Georgia Chenevix-Trench; Antonis C Antoniou; Laura Ottini; 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, Kim De Leeneer, Robin de Putter, Jesús Del Valle, Orland Diez, Yuan Chun Ding, Susan M Domchek, Alan Donaldson, Jacqueline Eason, Ros Eeles, Christoph Engel, D Gareth Evans, Lidia Feliubadaló, Florentia Fostira, Megan Frone, Debra Frost, David Gallagher, Andrea Gehrig, Sophie Giraud, Gord Glendon, Andrew K Godwin, David E Goldgar, Mark H Greene, Helen Gregory, Eva Gross, Eric Hahnen, Ute Hamann, Thomas V O Hansen, Helen Hanson, Julia Hentschel, Judit Horvath, Louise Izatt, Angel Izquierdo, Paul A James, Ramunas Janavicius, Uffe Birk Jensen, Oskar Th Johannsson, Esther M John, Gero Kramer, Lone Kroeldrup, Torben A Kruse, Charlotte Lautrup, Conxi Lazaro, Fabienne Lesueur, Adria Lopez-Fernández, Phuong L Mai, Siranoush Manoukian, Zoltan Matrai, Laura Matricardi, Kara N Maxwell, Noura Mebirouk, Alfons Meindl, Marco Montagna, Alvaro N Monteiro, Patrick J Morrison, Taru A Muranen, Alex Murray, Katherine L Nathanson, Susan L Neuhausen, Heli Nevanlinna, Tu Nguyen-Dumont, Dieter Niederacher, Edith Olah, Olufunmilayo I Olopade, Domenico Palli, Michael T Parsons, Inge Sokilde Pedersen, Bernard Peissel, Pedro Perez-Segura, Paolo Peterlongo, Annabeth H Petersen, Pedro Pinto, Mary E Porteous, Caroline Pottinger, Miquel Angel Pujana, Paolo Radice, Juliane Ramser, Johanna Rantala, Mark Robson, Mark T Rogers, Karina Rønlund, Andreas Rump, Ana María Sánchez de Abajo, Payal D Shah, Saba Sharif, Lucy E Side, Christian F Singer, Zsofia Stadler, Linda Steele, Dominique Stoppa-Lyonnet, Christian Sutter, Yen Yen Tan, Manuel R Teixeira, Alex Teulé, Darcy L Thull, Marc Tischkowitz, Amanda E Toland, Stefania Tommasi, Angela Toss, Alison H Trainer, Vishakha Tripathi, Virginia Valentini, Christi J van Asperen, Marta Venturelli, Alessandra Viel, Joseph Vijai, Lisa Walker, Shan Wang-Gohrke, Barbara Wappenschmidt, Anna Whaite, Ines Zanna, Kenneth Offit, Mads Thomassen, Fergus J Couch, Rita K Schmutzler, Jacques Simard, Douglas F Easton, Georgia Chenevix-Trench, Antonis C Antoniou, Laura Ottini^*, GEMO Study Collaborators

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

16 Citations (Scopus)

67 Downloads (Pure)

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.

Original language	English
Journal	Journal of the National Cancer Institute
Volume	114
Issue number	1
Pages (from-to)	109-122
Number of pages	14
ISSN	0027-8874
DOIs	https://doi.org/10.1093/jnci/djab147
Publication status	Published - 11 Jan 2022

Bibliographical note

Access to Document

10.1093/jnci/djab147Licence: CC BY 4.0

Barnes et al. (2022). Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk ScoresFinal published version, 6.24 MBLicence: CC BY 4.0

AUB Link

Search for the material in Aalborg University Library's search engine

Cite this

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. https://doi.org/10.1093/jnci/djab147

@article{523e8222deec41638b1d5d6b603a8d4a,

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.",

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 {De Leeneer}, Kim and {de Putter}, Robin and {Del Valle}, Jes{\'u}s and Orland Diez and Ding, {Yuan Chun} and Domchek, {Susan M} and Alan Donaldson and Jacqueline Eason and Ros Eeles and Christoph Engel and Evans, {D Gareth} and Lidia Feliubadal{\'o} and Florentia Fostira and Megan Frone and Debra Frost and David Gallagher and Andrea Gehrig and Sophie Giraud and Gord Glendon and Godwin, {Andrew K} and Goldgar, {David E} and Greene, {Mark H} and Helen Gregory and Eva Gross and Eric Hahnen and Ute Hamann and Hansen, {Thomas V O} and Helen Hanson and Julia Hentschel and Judit Horvath and Louise Izatt and Angel Izquierdo and James, {Paul A} and Ramunas Janavicius and Jensen, {Uffe Birk} and Johannsson, {Oskar Th} and John, {Esther M} and Gero Kramer and Lone Kroeldrup and Kruse, {Torben A} and Charlotte Lautrup and Conxi Lazaro and Fabienne Lesueur and Adria Lopez-Fern{\'a}ndez and Mai, {Phuong L} and Siranoush Manoukian and Zoltan Matrai and Laura Matricardi and Maxwell, {Kara N} and Noura Mebirouk and Alfons Meindl and Marco Montagna and Monteiro, {Alvaro N} and Morrison, {Patrick J} and Muranen, {Taru A} and Alex Murray and Nathanson, {Katherine L} and Neuhausen, {Susan L} and Heli Nevanlinna and Tu Nguyen-Dumont and Dieter Niederacher and Edith Olah and Olopade, {Olufunmilayo I} and Domenico Palli and Parsons, {Michael T} and Pedersen, {Inge Sokilde} and Bernard Peissel and Pedro Perez-Segura and Paolo Peterlongo and Petersen, {Annabeth H} and Pedro Pinto and Porteous, {Mary E} and Caroline Pottinger and Pujana, {Miquel Angel} and Paolo Radice and Juliane Ramser and Johanna Rantala and Mark Robson and Rogers, {Mark T} and Karina R{\o}nlund and Andreas Rump and {S{\'a}nchez de Abajo}, {Ana Mar{\'i}a} and Shah, {Payal D} and Saba Sharif and Side, {Lucy E} and Singer, {Christian F} and Zsofia Stadler and Linda Steele and Dominique Stoppa-Lyonnet and Christian Sutter and Tan, {Yen Yen} and Teixeira, {Manuel R} and Alex Teul{\'e} and Thull, {Darcy L} and Marc Tischkowitz and Toland, {Amanda E} and Stefania Tommasi and Angela Toss and Trainer, {Alison H} and Vishakha Tripathi and Virginia Valentini and {van Asperen}, {Christi J} and Marta Venturelli and Alessandra Viel and Joseph Vijai and Lisa Walker and Shan Wang-Gohrke and Barbara Wappenschmidt and Anna Whaite and Ines Zanna and Kenneth Offit and Mads Thomassen and Couch, {Fergus J} and Schmutzler, {Rita K} and Jacques Simard and Easton, {Douglas F} and Georgia Chenevix-Trench and Antoniou, {Antonis C} and Laura Ottini and {GEMO Study Collaborators}",

note = "{\textcopyright} The Author(s) 2021. Published by Oxford University Press.",

year = "2022",

month = jan,

day = "11",

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, De Leeneer, K, de Putter, R, Del Valle, J, Diez, O, Ding, YC, Domchek, SM, Donaldson, A, Eason, J, Eeles, R, Engel, C, Evans, DG, Feliubadaló, L, Fostira, F, Frone, M, Frost, D, Gallagher, D, Gehrig, A, Giraud, S, Glendon, G, Godwin, AK, Goldgar, DE, Greene, MH, Gregory, H, Gross, E, Hahnen, E, Hamann, U, Hansen, TVO, Hanson, H, Hentschel, J, Horvath, J, Izatt, L, Izquierdo, A, James, PA, Janavicius, R, Jensen, UB, Johannsson, OT, John, EM, Kramer, G, Kroeldrup, L, Kruse, TA, Lautrup, C, Lazaro, C, Lesueur, F, Lopez-Fernández, A, Mai, PL, Manoukian, S, Matrai, Z, Matricardi, L, Maxwell, KN, Mebirouk, N, Meindl, A, Montagna, M, Monteiro, AN, Morrison, PJ, Muranen, TA, Murray, A, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Nguyen-Dumont, T, Niederacher, D, Olah, E, Olopade, OI, Palli, D, Parsons, MT, Pedersen, IS, Peissel, B, Perez-Segura, P, Peterlongo, P, Petersen, AH, Pinto, P, Porteous, ME, Pottinger, C, Pujana, MA, Radice, P, Ramser, J, Rantala, J, Robson, M, Rogers, MT, Rønlund, K, Rump, A, Sánchez de Abajo, AM, Shah, PD, Sharif, S, Side, LE, Singer, CF, Stadler, Z, Steele, L, Stoppa-Lyonnet, D, Sutter, C, Tan, YY, Teixeira, MR, Teulé, A, Thull, DL, Tischkowitz, M, Toland, AE, Tommasi, S, Toss, A, Trainer, AH, Tripathi, V, Valentini, V, van Asperen, CJ, Venturelli, M, Viel, A, Vijai, J, Walker, L, Wang-Gohrke, S, Wappenschmidt, B, Whaite, A, Zanna, I, Offit, K, Thomassen, M, Couch, FJ, Schmutzler, RK, Simard, J, Easton, DF, Chenevix-Trench, G, Antoniou, AC, Ottini, L & 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, vol. 114, no. 1, pp. 109-122. https://doi.org/10.1093/jnci/djab147

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 - De Leeneer, Kim

AU - de Putter, Robin

AU - Del Valle, Jesús

AU - Diez, Orland

AU - Ding, Yuan Chun

AU - Domchek, Susan M

AU - Donaldson, Alan

AU - Eason, Jacqueline

AU - Eeles, Ros

AU - Engel, Christoph

AU - Evans, D Gareth

AU - Feliubadaló, Lidia

AU - Fostira, Florentia

AU - Frone, Megan

AU - Frost, Debra

AU - Gallagher, David

AU - Gehrig, Andrea

AU - Giraud, Sophie

AU - Glendon, Gord

AU - Godwin, Andrew K

AU - Goldgar, David E

AU - Greene, Mark H

AU - Gregory, Helen

AU - Gross, Eva

AU - Hahnen, Eric

AU - Hamann, Ute

AU - Hansen, Thomas V O

AU - Hanson, Helen

AU - Hentschel, Julia

AU - Horvath, Judit

AU - Izatt, Louise

AU - Izquierdo, Angel

AU - James, Paul A

AU - Janavicius, Ramunas

AU - Jensen, Uffe Birk

AU - Johannsson, Oskar Th

AU - John, Esther M

AU - Kramer, Gero

AU - Kroeldrup, Lone

AU - Kruse, Torben A

AU - Lautrup, Charlotte

AU - Lazaro, Conxi

AU - Lesueur, Fabienne

AU - Lopez-Fernández, Adria

AU - Mai, Phuong L

AU - Manoukian, Siranoush

AU - Matrai, Zoltan

AU - Matricardi, Laura

AU - Maxwell, Kara N

AU - Mebirouk, Noura

AU - Meindl, Alfons

AU - Montagna, Marco

AU - Monteiro, Alvaro N

AU - Morrison, Patrick J

AU - Muranen, Taru A

AU - Murray, Alex

AU - Nathanson, Katherine L

AU - Neuhausen, Susan L

AU - Nevanlinna, Heli

AU - Nguyen-Dumont, Tu

AU - Niederacher, Dieter

AU - Olah, Edith

AU - Olopade, Olufunmilayo I

AU - Palli, Domenico

AU - Parsons, Michael T

AU - Pedersen, Inge Sokilde

AU - Peissel, Bernard

AU - Perez-Segura, Pedro

AU - Peterlongo, Paolo

AU - Petersen, Annabeth H

AU - Pinto, Pedro

AU - Porteous, Mary E

AU - Pottinger, Caroline

AU - Pujana, Miquel Angel

AU - Radice, Paolo

AU - Ramser, Juliane

AU - Rantala, Johanna

AU - Robson, Mark

AU - Rogers, Mark T

AU - Rønlund, Karina

AU - Rump, Andreas

AU - Sánchez de Abajo, Ana María

AU - Shah, Payal D

AU - Sharif, Saba

AU - Side, Lucy E

AU - Singer, Christian F

AU - Stadler, Zsofia

AU - Steele, Linda

AU - Stoppa-Lyonnet, Dominique

AU - Sutter, Christian

AU - Tan, Yen Yen

AU - Teixeira, Manuel R

AU - Teulé, Alex

AU - Thull, Darcy L

AU - Tischkowitz, Marc

AU - Toland, Amanda E

AU - Tommasi, Stefania

AU - Toss, Angela

AU - Trainer, Alison H

AU - Tripathi, Vishakha

AU - Valentini, Virginia

AU - van Asperen, Christi J

AU - Venturelli, Marta

AU - Viel, Alessandra

AU - Vijai, Joseph

AU - Walker, Lisa

AU - Wang-Gohrke, Shan

AU - Wappenschmidt, Barbara

AU - Whaite, Anna

AU - Zanna, Ines

AU - Offit, Kenneth

AU - Thomassen, Mads

AU - Couch, Fergus J

AU - Schmutzler, Rita K

AU - Simard, Jacques

AU - Easton, Douglas F

AU - Chenevix-Trench, Georgia

AU - Antoniou, Antonis C

AU - Ottini, Laura

AU - GEMO Study Collaborators

PY - 2022/1/11

Y1 - 2022/1/11

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.

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

ER -

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

Abstract

Bibliographical note

Access to Document

AUB Link

Other files and links

Fingerprint

Cite this