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00925njm 22002777a 4500 dc Lecarpentier, Julie author Silvestri, Valentina author Kuchenbaecker, Karoline B author Barrowdale, Daniel author Dennis, Joe author McGuffog, Lesley author Soucy, Penny author Leslie, Goska author Rizzolo, Piera author Navazio, Anna Sara author Valentini, Virginia author Zelli, Veronica author Lee, Andrew author Amin Al Olama, Ali author Tyrer, Jonathan P author Southey, Melissa author John, Esther M author Conner, Thomas A author Goldgar, David E author Buys, Saundra S author Janavicius, Ramunas author Steele, Linda author Ding, Yuan Chun author Neuhausen, Susan L author Hansen, Thomas V O author Osorio, Ana author Weitzel, Jeffrey N author Toss, Angela author Medici, Veronica author Cortesi, Laura author Zanna, Ines author Palli, Domenico author Radice, Paolo author Manoukian, Siranoush author Peissel, Bernard author Azzollini, Jacopo author Viel, Alessandra author Cini, Giulia author Damante, Giuseppe author Tommasi, Stefania author Peterlongo, Paolo author Fostira, Florentia author Hamann, Ute author Evans, D Gareth author Henderson, Alex author Brewer, Carole author Eccles, Diana author Cook, Jackie author Ong, Kai-Ren author Walker, Lisa author Side, Lucy E author Porteous, Mary E author Davidson, Rosemarie author Hodgson, Shirley author Frost, Debra author Adlard, Julian author Izatt, Louise author Eeles, Ros author Ellis, Steve author Tischkowitz, Marc author Godwin, Andrew K author Meindl, Alfons author Gehrig, Andrea author Dworniczak, Bernd author Sutter, Christian author Engel, Christoph author Niederacher, Dieter author Steinemann, Doris author Hahnen, Eric author Hauke, Jan author Rhiem, Kerstin author Kast, Karin author Arnold, Norbert author Ditsch, Nina author Wang-Gohrke, Shan author Wappenschmidt, Barbara author Wand, Dorothea author Lasset, Christine author Stoppa-Lyonnet, Dominique author Belotti, Muriel author Damiola, Francesca author Barjhoux, Laure author Mazoyer, Sylvie author Van Heetvelde, Mattias author Poppe, Bruce author De Leeneer, Kim author Claes, Kathleen B M author de la Hoya, Miguel author Garcia-Barberan, Vanesa author Caldes, Trinidad author Perez Segura, Pedro author Kiiski, Johanna I author Aittomäki, Kristiina author Khan, Sofia author Nevanlinna, Heli author van Asperen, Christi J author Vaszko, Tibor author Kasler, Miklos author Olah, Edith author Balmaña, Judith author Gutiérrez-Enríquez, Sara author Diez, Orland author Teulé, Alex author Izquierdo, Angel author Darder, Esther author Brunet, Joan author Del Valle, Jesús author Feliubadalo, Lidia author Pujana, Miquel Angel author Lazaro, Conxi author Arason, Adalgeir author Agnarsson, Bjarni A author Johannsson, Oskar Th author Barkardottir, Rosa B author Alducci, Elisa author Tognazzo, Silvia author Montagna, Marco author Teixeira, Manuel R author Pinto, Pedro author Spurdle, Amanda B author Holland, Helene author Lee, Jong Won author Lee, Min Hyuk author Lee, Jihyoun author Kim, Sung-Won author Kang, Eunyoung author Kim, Zisun author Sharma, Priyanka author Rebbeck, Timothy R author Vijai, Joseph author Robson, Mark author Lincoln, Anne author Musinsky, Jacob author Gaddam, Pragna author Tan, Yen Y author Berger, Andreas author Singer, Christian F author Loud, Jennifer T author Greene, Mark H author Mulligan, Anna Marie author Glendon, Gord author Andrulis, Irene L author Toland, Amanda Ewart author Senter, Leigha author Bojesen, Anders author Nielsen, Henriette Roed author Skytte, Anne-Bine author Sunde, Lone author Jensen, Uffe Birk author Pedersen, Inge Sokilde author Krogh, Lotte author Kruse, Torben A author Caligo, Maria A author Yoon, Sook-Yee author Teo, Soo-Hwang author von Wachenfeldt, Anna author Huo, Dezheng author Nielsen, Sarah M author Olopade, Olufunmilayo I author Nathanson, Katherine L author Domchek, Susan M author Lorenchick, Christa author Jankowitz, Rachel C author Campbell, Ian author James, Paul author Mitchell, Gillian author Orr, Nick author Park, Sue Kyung author Thomassen, Mads author Offit, Kenneth author Couch, Fergus J author Simard, Jacques author Easton, Douglas F author Chenevix-Trench, Georgia author Schmutzler, Rita K author Antoniou, Antonis C author Ottini, Laura author 2017-07-10 Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigated-for the first time to our knowledge-associations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/ 2 mutations and implications for cancer risk prediction. Materials and Methods We genotyped 1,802 male carriers of BRCA1/2 mutations from the Consortium of Investigators of Modifiers of BRCA1/2 by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of BRCA1/2 mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights. Results In male carriers of BRCA1/2 mutations, PRS that was based on 88 female breast cancer susceptibility variants was associated with breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19 to 1.56; P = 8.6 × 10-6). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95% CI, 1.35 to 1.81; P = 3.2 × 10-9). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7% to 26% for carriers of BRCA1 mutations and from 19% to 61% for carriers of BRCA2 mutations, respectively. Conclusion PRSs may provide informative cancer risk stratification for male carriers of BRCA1/2 mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management. J Clin Oncol. 2017;35(20):2240-2250 10.1200/JCO.2016.69.4935 1527-7755 0732-183X Journal of clinical oncology : official journal of the American Society of Clinical Oncology 28448241 http://hdl.handle.net/20.500.12105/8384 Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores