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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; et al. 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, K-R; Walker, L; Side, LE; Porteous, ME; Davidson, R; Hodgson, S; Frost, D; Adlard, J; Izatt, L; Eeles, R; Ellis, S; Tischkowitz, M; EMBRACE; 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; GEMO Study Collaborators; 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; HEBON; 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; KConFab Investigators; Lee, JW; Lee, MH; Lee, J; Kim, S-W; 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, A-B; Sunde, L; Jensen, UB; Pedersen, IS; Krogh, L; Kruse, TA; Caligo, MA; Yoon, S-Y; Teo, S-H; 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 (2017) Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores. J Clin Oncol, 35 (20). pp. 2240-2250. ISSN 1527-7755 https://doi.org/10.1200/JCO.2016.69.4935
SGUL Authors: Hodgson, Shirley Victoria

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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.

Item Type: Article
Additional Information: © 2017 by American Society of Clinical Oncology. Licensed under the Creative Commons Attribution 4.0 License.
Keywords: Oncology & Carcinogenesis, 1112 Oncology And Carcinogenesis
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cell Sciences (INCCCS)
Journal or Publication Title: J Clin Oncol
ISSN: 1527-7755
Language: eng
Dates:
DateEvent
10 July 2017Published
27 April 2017Published Online
2 March 2017Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
C1287/A1656Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
C12292/A20861Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
C12292/A11174Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
C1287/A10118Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
C1287/A11990Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
PubMed ID: 28448241
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/108994
Publisher's version: https://doi.org/10.1200/JCO.2016.69.4935

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