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 Aittomaki; Irene L Andrulis; Adalgeir Arason; Norbert Arnold; Bernd Auber; Jacopo Azzollini; Judith Balmana; Rosa B Barkardottir; Daniel Barrowdale; Julian Barwell; Muriel Belotti; Javier Benitez; Pascaline Berthet; Susanne E Boonen; Ake Borg; Aniko Bozsik; Angela F Brady; Paul Brennan; Carole Brewer; Joan Brunet; Agostino Bucalo; Saundra S Buys; Trinidad Caldes; 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; Jesus Del Valle; Orland Diez; Yuan Chun Ding; Susan M Domchek; Alan Donaldson; Jacqueline Eason; Ros Eeles; Christoph Engel; D. Gareth Evans; Lidia Feliubadalo; 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; Ramūnas Janavičius; Uffe Birk Jensen; Oskar Th Johannsson; Esther M John; Gero Kramer; Lone Kroeldrup; Torben A Kruse; Charlotte Lautrup; Conxi Lazaro; Fabienne Lesueur; Adria Lopez-Fernandez; 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 Maria Sanchez 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 Teule; 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

doi:10.1093/jnci/djab147

Title	Breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers using polygenic risk scores /
Authors	Barnes, Daniel R ; Silvestri, Valentina ; Leslie, Goska ; McGuffog, Lesley ; Dennis, Joe ; Yang, Xin ; Adlard, Julian ; Agnarsson, Bjarni A ; Ahmed, Munaza ; Aittomaki, Kristiina ; Andrulis, Irene L ; Arason, Adalgeir ; Arnold, Norbert ; Auber, Bernd ; Azzollini, Jacopo ; 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 ; 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 ; De Putter, Robin ; Del Valle, Jesus ; Diez, Orland ; Ding, Yuan Chun ; Domchek, Susan M ; Donaldson, Alan ; Eason, Jacqueline ; Eeles, Ros ; Engel, Christoph ; Evans, D. Gareth ; Feliubadalo, Lidia ; 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 ; Janavičius, Ramūnas ; Jensen, Uffe Birk ; 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 ; Nguyen-Dumont, Tu ; Niederacher, Dieter ; Olah, Edith ; Olopade, Olufunmilayo I ; Palli, Domenico ; Parsons, Michael T ; Pedersen, Inge Sokilde ; Peissel, Bernard ; Perez-Segura, Pedro ; Peterlongo, Paolo ; Petersen, Annabeth H ; Pinto, Pedro ; Porteous, Mary E ; Pottinger, Caroline ; Pujana, Miquel Angel ; Radice, Paolo ; Ramser, Juliane ; Rantala, Johanna ; Robson, Mark ; Rogers, Mark T ; Rønlund, 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 ; Easton, Douglas F ; Chenevix-Trench, Georgia ; Antoniou, Antonis C ; Ottini, Laura
DOI	10.1093/jnci/djab147
Full Text
Is Part of	JNCI-Journal of the National Cancer Institute.. Oxford : Oxford University Press. 2022, vol. 114, iss. 1, p. 109-122.. ISSN 0027-8874. eISSN 1460-2105
Abstract [eng]	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.
Published	Oxford : Oxford University Press
Type	Journal article
Language	English
Publication date	2022
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„Breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers using polygenic risk scores /“