Barnes, Daniel R., Silvestri, Valentina, Leslie, Goska ORCID: 0000-0001-5756-6222, McGuffog, Lesley, Dennis, Joe, Yang, Xin, Adlard, Julian ORCID: 0000-0002-1693-0435, Agnarsson, Bjarni A., Ahmed, Munaza, Aittomaki, Kristiina, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Auber, Bernd, Azzollini, Jacopo ORCID: 0000-0002-9364-9778, Balmana, Judith, Barkardottir, Rosa B., Barrowdale, Daniel, Barwell, Julian, Belotti, Muriel, Benitez, Javier, Berthet, Pascaline, Boonen, Susanne E., Borg, Ake, Bozsik, Aniko, Brady, Angela F., Brennan, Paul, Brewer, Carole, Brunet, Joan ORCID: 0000-0003-1945-3512, Bucalo, Agostino, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Cassingham, Hayley, Christensen, Lise Lotte, Cini, Giulia, Claes, Kathleen B. M., Cook, Jackie, Coppa, Anna, Cortesi, Laura, Damante, Giuseppe, Darder, Esther, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim ORCID: 0000-0002-9319-411X, de Putter, Robin, Del Valle, Jesus, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Donaldson, Alan, Eason, Jacqueline, Eeles, Ros, Engel, Christoph ORCID: 0000-0002-7247-282X, Evans, D. Gareth, Feliubadalo, Lidia ORCID: 0000-0002-1736-0112, Fostira, Florentia, Frone, Megan, Frost, Debra, Gallagher, David, Gehrig, Andrea, Giraud, Sophie, Glendon, Gord, Godwin, Andrew K., Goldgar, David E., Greene, Mark H., Gregory, Helen, Gross, Eva, Hahnen, Eric, Hamann, Ute, Hansen, Thomas V. O., Hanson, Helen, Hentschel, Julia, Horvath, Judit, Izatt, Louise, Izquierdo, Angel, James, Paul A., Janavicius, Ramunas, Jensen, Uffe Birk ORCID: 0000-0002-6205-6355, Johannsson, Oskar Th, John, Esther M., Kramer, Gero, Kroeldrup, Lone, Kruse, Torben A., Lautrup, Charlotte, Lazaro, Conxi, Lesueur, Fabienne, Lopez-Fernandez, Adria, Mai, Phuong L., Manoukian, Siranoush, Matrai, Zoltan, Matricardi, Laura, Maxwell, Kara N., Mebirouk, Noura, Meindl, Alfons, Montagna, Marco, Monteiro, Alvaro N., Morrison, Patrick J., Muranen, Taru A., Murray, Alex, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Niederacher, Dieter, Olah, Edith, Olopade, Olufunmilayo, I, Palli, Domenico, Parsons, Michael T., Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Peterlongo, Paolo ORCID: 0000-0001-6951-6855, Petersen, Annabeth H., Pinto, Pedro, Porteous, Mary E., Pottinger, Caroline, Pujana, Miquel Angel, Radice, Paolo, Ramser, Juliane, Rantala, Johanna, Robson, Mark, Rogers, Mark T., Ronlund, Karina, Rump, Andreas, Sanchez de Abajo, Ana Maria, Shah, Payal D., Sharif, Saba, Side, Lucy E., Singer, Christian F., Stadler, Zsofia, Steele, Linda, Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen Yen, Teixeira, Manuel R., Teule, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Tommasi, Stefania, Toss, Angela, Trainer, Alison H., Tripathi, Vishakha, Valentini, Virginia, van Asperen, Christi J., Venturelli, Marta, Viel, Alessandra, Vijai, Joseph, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Whaite, Anna, Zanna, Ines, Offit, Kenneth, Thomassen, Mads, Couch, Fergus J., Schmutzler, Rita K., Simard, Jacques ORCID: 0000-0001-6906-3390, Easton, Douglas F., Chenevix-Trench, Georgia ORCID: 0000-0002-1878-2587, Antoniou, Antonis C. and Ottini, Laura (2022). Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores. JNCI-J. Natl. Cancer Inst., 114 (1). S. 109 - 123. CARY: OXFORD UNIV PRESS INC. ISSN 1460-2105

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Barnes, Daniel R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Silvestri, ValentinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leslie, GoskaUNSPECIFIEDorcid.org/0000-0001-5756-6222UNSPECIFIED
McGuffog, LesleyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dennis, JoeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yang, XinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Adlard, JulianUNSPECIFIEDorcid.org/0000-0002-1693-0435UNSPECIFIED
Agnarsson, Bjarni A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ahmed, MunazaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aittomaki, KristiinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andrulis, Irene L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arason, AdalgeirUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arnold, NorbertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Auber, BerndUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Azzollini, JacopoUNSPECIFIEDorcid.org/0000-0002-9364-9778UNSPECIFIED
Balmana, JudithUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barkardottir, Rosa B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barrowdale, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barwell, JulianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Belotti, MurielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benitez, JavierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berthet, PascalineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boonen, Susanne E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borg, AkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bozsik, AnikoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brady, Angela F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brennan, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brewer, CaroleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brunet, JoanUNSPECIFIEDorcid.org/0000-0003-1945-3512UNSPECIFIED
Bucalo, AgostinoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buys, Saundra S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caldes, TrinidadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caligo, Maria A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Campbell, IanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cassingham, HayleyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Christensen, Lise LotteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cini, GiuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Claes, Kathleen B. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cook, JackieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Coppa, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cortesi, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Damante, GiuseppeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Darder, EstherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Davidson, RosemarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de la Hoya, MiguelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Leeneer, KimUNSPECIFIEDorcid.org/0000-0002-9319-411XUNSPECIFIED
de Putter, RobinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Del Valle, JesusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Diez, OrlandUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ding, Yuan ChunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Domchek, Susan M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Donaldson, AlanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eason, JacquelineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eeles, RosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Engel, ChristophUNSPECIFIEDorcid.org/0000-0002-7247-282XUNSPECIFIED
Evans, D. GarethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Feliubadalo, LidiaUNSPECIFIEDorcid.org/0000-0002-1736-0112UNSPECIFIED
Fostira, FlorentiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frone, MeganUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frost, DebraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gallagher, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gehrig, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Giraud, SophieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Glendon, GordUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Godwin, Andrew K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goldgar, David E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Greene, Mark H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gregory, HelenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gross, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hahnen, EricUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hamann, UteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hansen, Thomas V. O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hanson, HelenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hentschel, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Horvath, JuditUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Izatt, LouiseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Izquierdo, AngelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
James, Paul A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Janavicius, RamunasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jensen, Uffe BirkUNSPECIFIEDorcid.org/0000-0002-6205-6355UNSPECIFIED
Johannsson, Oskar ThUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
John, Esther M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kramer, GeroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kroeldrup, LoneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kruse, Torben A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lautrup, CharlotteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lazaro, ConxiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lesueur, FabienneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lopez-Fernandez, AdriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mai, Phuong L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Manoukian, SiranoushUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Matrai, ZoltanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Matricardi, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maxwell, Kara N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mebirouk, NouraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meindl, AlfonsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Montagna, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Monteiro, Alvaro N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morrison, Patrick J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muranen, Taru A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Murray, AlexUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nathanson, Katherine L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neuhausen, Susan L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nevanlinna, HeliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Niederacher, DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Olah, EdithUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Olopade, Olufunmilayo, IUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Palli, DomenicoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Parsons, Michael T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pedersen, Inge SokildeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peissel, BernardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perez-Segura, PedroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peterlongo, PaoloUNSPECIFIEDorcid.org/0000-0001-6951-6855UNSPECIFIED
Petersen, Annabeth H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pinto, PedroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Porteous, Mary E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pottinger, CarolineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pujana, Miquel AngelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Radice, PaoloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramser, JulianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rantala, JohannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Robson, MarkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rogers, Mark T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ronlund, KarinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rump, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sanchez de Abajo, Ana MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shah, Payal D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sharif, SabaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Side, Lucy E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Singer, Christian F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stadler, ZsofiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steele, LindaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stoppa-Lyonnet, DominiqueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sutter, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tan, Yen YenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teixeira, Manuel R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teule, AlexUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thull, Darcy L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tischkowitz, MarcUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toland, Amanda E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tommasi, StefaniaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toss, AngelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trainer, Alison H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tripathi, VishakhaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Valentini, VirginiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Asperen, Christi J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Venturelli, MartaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Viel, AlessandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vijai, JosephUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walker, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang-Gohrke, ShanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wappenschmidt, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Whaite, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zanna, InesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Offit, KennethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomassen, MadsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Couch, Fergus J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmutzler, Rita K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simard, JacquesUNSPECIFIEDorcid.org/0000-0001-6906-3390UNSPECIFIED
Easton, Douglas F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chenevix-Trench, GeorgiaUNSPECIFIEDorcid.org/0000-0002-1878-2587UNSPECIFIED
Antoniou, Antonis C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ottini, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-608441
DOI: 10.1093/jnci/djab147
Journal or Publication Title: JNCI-J. Natl. Cancer Inst.
Volume: 114
Number: 1
Page Range: S. 109 - 123
Date: 2022
Publisher: OXFORD UNIV PRESS INC
Place of Publication: CARY
ISSN: 1460-2105
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MUTATION CARRIERS; ASSOCIATION; OVARIANMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60844

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