Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores.
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Authors
Lecarpentier, JulieSilvestri, Valentina
Kuchenbaecker, Karoline B
Barrowdale, Daniel
Dennis, Joe
McGuffog, Lesley
Soucy, Penny
Leslie, Goska
Rizzolo, Piera
Navazio, Anna Sara
Valentini, Virginia
Gutiérrez-Enríquez, Sara
Diez, Orland
Teulé, Alex
Izquierdo, Angel
Darder, Esther
Brunet, Joan
Del Valle, Jesús
Feliubadalo, Lidia
Pujana, Miquel Angel
Lazaro, Conxi
Zelli, Veronica
Arason, Adalgeir
Agnarsson, Bjarni A
Johannsson, Oskar Th
Barkardottir, Rosa B
Alducci, Elisa
Tognazzo, Silvia
Montagna, Marco
Teixeira, Manuel R
Pinto, Pedro
Spurdle, Amanda B
Lee, Andrew
Holland, Helene
Lee, Jong Won
Lee, Min Hyuk
Lee, Jihyoun
Kim, Sung-Won
Kang, Eunyoung
Kim, Zisun
Sharma, Priyanka
Rebbeck, Timothy R
Vijai, Joseph
Amin Al Olama, Ali
Robson, Mark
Lincoln, Anne
Musinsky, Jacob
Gaddam, Pragna
Tan, Yen Y
Berger, Andreas
Singer, Christian F
Loud, Jennifer T
Greene, Mark H
Mulligan, Anna Marie
Tyrer, Jonathan P
Glendon, Gord
Andrulis, Irene L
Toland, Amanda Ewart
Senter, Leigha
Bojesen, Anders
Nielsen, Henriette Roed
Skytte, Anne-Bine
Sunde, Lone
Jensen, Uffe Birk
Pedersen, Inge Sokilde
Southey, Melissa
Krogh, Lotte
Kruse, Torben A
Caligo, Maria A
Yoon, Sook-Yee
Teo, Soo-Hwang
von Wachenfeldt, Anna
Huo, Dezheng
Nielsen, Sarah M
Olopade, Olufunmilayo I
Nathanson, Katherine L
John, Esther M
Domchek, Susan M
Lorenchick, Christa
Jankowitz, Rachel C
Campbell, Ian
James, Paul
Mitchell, Gillian
Orr, Nick
Park, Sue Kyung
Thomassen, Mads
Offit, Kenneth
Conner, Thomas A
Couch, Fergus J
Simard, Jacques
Easton, Douglas F
Chenevix-Trench, Georgia
Schmutzler, Rita K
Antoniou, Antonis C
Ottini, Laura
Goldgar, David E
Buys, Saundra S
Janavicius, Ramunas
Steele, Linda
Ding, Yuan Chun
Neuhausen, Susan L
Hansen, Thomas V O
Osorio, Ana
Weitzel, Jeffrey N
Toss, Angela
Medici, Veronica
Cortesi, Laura
Zanna, Ines
Palli, Domenico
Radice, Paolo
Manoukian, Siranoush
Peissel, Bernard
Azzollini, Jacopo
Viel, Alessandra
Cini, Giulia
Damante, Giuseppe
Tommasi, Stefania
Peterlongo, Paolo
Fostira, Florentia
Hamann, Ute
Evans, D Gareth
Henderson, Alex
Brewer, Carole
Eccles, Diana
Cook, Jackie
Ong, Kai-Ren
Walker, Lisa
Side, Lucy E
Porteous, Mary E
Davidson, Rosemarie
Hodgson, Shirley
Frost, Debra
Adlard, Julian
Izatt, Louise
Eeles, Ros
Ellis, Steve
Tischkowitz, Marc
Godwin, Andrew K
Meindl, Alfons
Gehrig, Andrea
Dworniczak, Bernd
Sutter, Christian
Engel, Christoph
Niederacher, Dieter
Steinemann, Doris
Hahnen, Eric
Hauke, Jan
Rhiem, Kerstin
Kast, Karin
Arnold, Norbert
Ditsch, Nina
Wang-Gohrke, Shan
Wappenschmidt, Barbara
Wand, Dorothea
Lasset, Christine
Stoppa-Lyonnet, Dominique
Belotti, Muriel
Damiola, Francesca
Barjhoux, Laure
Mazoyer, Sylvie
Van Heetvelde, Mattias
Poppe, Bruce
De Leeneer, Kim
Claes, Kathleen B M
de la Hoya, Miguel
Garcia-Barberan, Vanesa
Caldes, Trinidad
Perez Segura, Pedro
Kiiski, Johanna I
Aittomäki, Kristiina
Khan, Sofia
Nevanlinna, Heli
van Asperen, Christi J
Vaszko, Tibor
Kasler, Miklos
Olah, Edith
Balmaña, Judith
Issue Date
2017-07-10
Metadata
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Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores. 2017, 35 (20):2240-2250 J. Clin. Oncol.Abstract
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.Description
To access publisher's full text version of this article click on the hyperlink belowAdditional Links
http://ascopubs.org/doi/pdf/10.1200/JCO.2016.69.4935Rights
Archived with thanks to Journal of clinical oncology : official journal of the American Society of Clinical Oncologyae974a485f413a2113503eed53cd6c53
10.1200/JCO.2016.69.4935
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