Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores

• Type: Article in International Scientific Journal
• Date: 2017

Authors

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

Journal

Title: Journal of Clinical Oncology

Vol. 35

Pages: 2240-+

ISSN: 0732-183X

Publisher: American Society of Clinical Oncology

Indexing

ISI Web of Knowledge - 101 Citations

Scopus - 105 Citations

Other information

Authenticus ID: P-00R-AQ4

DOI: 10.1200/jco.2016.69.4935

Abstract (EN): PurposeBRCA1/2 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 investigatedfor the first time to our knowledgeassociations 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 MethodsWe 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.ResultsIn 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 x 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 x 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.ConclusionPRSs 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 17