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

Journal: Journal Of The National Cancer Institute

Published: February 16, 2021

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.

Authors

Daniel Barnes, Valentina Silvestri, Goska Leslie, Lesley Mcguffog, Joe Dennis, Xin Yang, Julian Adlard, Bjarni Agnarsson, Munaza Ahmed, Kristiina Aittomäki, Irene Andrulis, Adalgeir Arason, Norbert Arnold, Bernd Auber, Jacopo Azzollini, Judith Balmaña, Rosa Barkardottir, Daniel Barrowdale, Julian Barwell, Muriel Belotti, Javier Benitez, Pascaline Berthet, Susanne Boonen, Åke Borg, Aniko Bozsik, Angela Brady, Paul Brennan, Carole Brewer, Joan Brunet, Agostino Bucalo, Saundra Buys, Trinidad Caldés, Maria Caligo, Ian Campbell, Hayley Cassingham, Lise Christensen, Giulia Cini, Kathleen B Claes, Laura Cortesi, Giuseppe Damante, Esther Darder, Rosemarie Davidson, Miguel De La Hoya, Kim De Leeneer, Robin De Putter, Jesús Del Valle, Orland Diez, Yuan Ding, Susan Domchek, Alan Donaldson, Jacqueline Eason, Ros Eeles, Christoph Engel, D Evans, Lidia Feliubadaló, Florentia Fostira, Megan Frone, Debra Frost, David Gallagher, Andrea Gehrig, Sophie Giraud, Gord Glendon, Andrew Godwin, David Goldgar, Mark Greene, Helen Gregory, Eva Gross, Eric Hahnen, Ute Hamann, Thomas Hansen, Helen Hanson, Julia Hentschel, Judit Horvath, Louise Izatt, Angel Izquierdo, Uffe Jensen, Oskar Johannsson, Esther John, Gero Kramer, Lone Kroeldrup, Torben Kruse, Charlotte Lautrup, Conxi Lazaro, Fabienne Lesueur, Adria Lopez Fernández, Phuong Mai, Siranoush Manoukian, Zoltan Matrai, Laura Matricardi, Kara Maxwell, Noura Mebirouk, Alfons Meindl, Marco Montagna, Alvaro Monteiro, Patrick Morrison, Taru Muranen, Alex Murray, Katherine Nathanson, Susan Neuhausen, Heli Nevanlinna, Tu Nguyen Dumont, Dieter Niederacher, Edith Olah, Olufunmilayo Olopade, Domenico Palli, Michael Parsons, Inge Pedersen, Bernard Peissel, Pedro Perez Segura, Paolo Peterlongo, Annabeth Petersen, Pedro Pinto, Mary Porteous, Caroline Pottinger, Miquel Pujana, Paolo Radice, Juliane Ramser, Johanna Rantala, Mark Robson, Mark Rogers, Karina Rønlund, Andreas Rump, Ana Sánchez De Abajo, Payal Shah, Saba Sharif, Lucy Side, Christian Singer, Zsofia Stadler, Linda Steele, Dominique Stoppa Lyonnet, Christian Sutter, Yen Tan, Manuel Teixeira, Alex Teulé, Darcy Thull, Marc Tischkowitz, Amanda Toland, Stefania Tommasi, Angela Toss, Alison Trainer, Vishakha Tripathi, Virginia Valentini, Christi Van Asperen, Marta Venturelli, Alessandra Viel, Joseph Vijai, Lisa Walker, Shan Wang Gohrke, Barbara Wappenschmidt, Anna Whaite, Ines Zanna, Kenneth Offit, Mads Thomassen, Fergus Couch, Rita Schmutzler, Jacques Simard, Douglas Easton, Georgia Chenevix Trench, Antonis Antoniou, Laura Ottini

Relevant Conditions

Prostate Cancer, Breast Cancer

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

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