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    Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2017 Apr 27. doi: 10.1200/JCO.2016.69.4935
    Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores.
    Lecarpentier J,  Silvestri V,  Kuchenbaecker KB,  Barrowdale D,  Dennis J,  McGuffog L,  Soucy P,  Leslie G,  Rizzolo P,  Navazio AS,  Valentini V,  Zelli V,  Lee A,  Amin Al Olama A,  Tyrer JP,  Southey M,  John EM,  Conner TA,  Goldgar DE,  Buys SS,  Janavicius R,  Steele L,  Ding YC,  Neuhausen SL,  Hansen TVO,  Osorio A,  Weitzel JN,  Toss A,  Medici V,  Cortesi L,  Zanna I,  Palli D,  Radice P,  Manoukian S,  Peissel B,  Azzollini J,  Viel A,  Cini G,  Damante G,  Tommasi S,  Peterlongo P,  Fostira F,  Hamann U,  Evans DG,  Henderson A,  Brewer C,  Eccles D,  Cook J,  Ong KR,  Walker L,  Side LE,  Porteous ME,  Davidson R,  Hodgson S,  Frost D,  Adlard J,  Izatt L,  Eeles R,  Ellis S,  Tischkowitz M,  Godwin AK,  Meindl A,  Gehrig A,  Dworniczak B,  Sutter C,  Engel C,  Niederacher D,  Steinemann D,  Hahnen E,  Hauke J,  Rhiem K,  Kast K,  Arnold N,  Ditsch N,  Wang-Gohrke S,  Wappenschmidt B,  Wand D,  Lasset C,  Stoppa-Lyonnet D,  Belotti M,  Damiola F,  Barjhoux L,  Mazoyer S,  Van Heetvelde M,  Poppe B,  De Leeneer K,  Claes KBM,  de la Hoya M,  Garcia-Barberan V,  Caldes T,  Perez Segura P,  Kiiski JI,  Aittomäki K,  Khan S,  Nevanlinna H,  van Asperen CJ,  Vaszko T,  Kasler M,  Olah E,  Balmaña J,  Gutiérrez-Enríquez S,  Diez O,  Teulé A,  Izquierdo A,  Darder E,  Brunet J,  Del Valle J,  Feliubadalo L,  Pujana MA,  Lazaro C,  Arason A,  Agnarsson BA,  Johannsson OT,  Barkardottir RB,  Alducci E,  Tognazzo S,  Montagna M,  Teixeira MR,  Pinto P,  Spurdle AB,  Holland H,  Lee JW,  Lee MH,  Lee J,  Kim SW,  Kang E,  Kim Z,  Sharma P,  Rebbeck TR,  Vijai J,  Robson M,  Lincoln A,  Musinsky J,  Gaddam P,  Tan YY,  Berger A,  Singer CF,  Loud JT,  Greene MH,  Mulligan AM,  Glendon G,  Andrulis IL,  Toland AE,  Senter L,  Bojesen A,  Nielsen HR,  Skytte AB,  Sunde L,  Jensen UB,  Pedersen IS,  Krogh L,  Kruse TA,  Caligo MA,  Yoon SY,  Teo SH,  von Wachenfeldt A,  Huo D,  Nielsen SM,  Olopade OI,  Nathanson KL,  Domchek SM,  Lorenchick C,  Jankowitz RC,  Campbell I,  James P,  Mitchell G,  Orr N,  Park SK,  Thomassen M,  Offit K,  Couch FJ,  Simard J,  Easton DF,  Chenevix-Trench G,  Schmutzler RK,  Antoniou AC,  Ottini L
    Author information
    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.


    Publikations ID: 28448241
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