Prediction of breast and prostate cancer risks in male BRCA1 and BRCA2 mutation carriers using polygenic risk scores.
Amin Al Olama, A
Evans, D Gareth R
Van Heetvelde, M
De Leeneer, K
de la Hoya, M
Perez Segura, P
van Asperen, C
Del Valle, J
von Wachenfeldt, A
MetadataShow full item record
AbstractPurpose 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.
CitationPrediction of breast and prostate cancer risks in male BRCA1 and BRCA2 mutation carriers using polygenic risk scores. 2017 J Clin Oncol
JournalJournal of Clinical Oncology
- Evaluation of Polygenic Risk Scores for Breast and Ovarian Cancer Risk Prediction in BRCA1 and BRCA2 Mutation Carriers.
- Authors: Kuchenbaecker KB, McGuffog L, Barrowdale D, Lee A, Soucy P, Dennis J, Domchek SM, Robson M, Spurdle AB, Ramus SJ, Mavaddat N, Terry MB, Neuhausen SL, Schmutzler RK, Simard J, Pharoah PDP, Offit K, Couch FJ, Chenevix-Trench G, Easton DF, Antoniou AC
- Issue date: 2017 Jul 1
- Increased risk of male cancer and identification of a potential prostate cancer cluster region in BRCA2.
- Authors: Roed Nielsen H, Petersen J, Therkildsen C, Skytte AB, Nilbert M
- Issue date: 2016
- The impact of a panel of 18 SNPs on breast cancer risk in women attending a UK familial screening clinic: a case-control study.
- Authors: Evans DG, Brentnall A, Byers H, Harkness E, Stavrinos P, Howell A, FH-risk study Group., Newman WG, Cuzick J
- Issue date: 2017 Feb
- Common variants associated with breast cancer in genome-wide association studies are modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers.
- Authors: Wang X, Pankratz VS, Fredericksen Z, Tarrell R, Karaus M, McGuffog L, Pharaoh PD, Ponder BA, Dunning AM, Peock S, Cook M, Oliver C, Frost D, EMBRACE., Sinilnikova OM, Stoppa-Lyonnet D, Mazoyer S, Houdayer C, GEMO., Hogervorst FB, Hooning MJ, Ligtenberg MJ, HEBON., Spurdle A, Chenevix-Trench G, kConFab., Schmutzler RK, Wappenschmidt B, Engel C, Meindl A, Domchek SM, Nathanson KL, Rebbeck TR, Singer CF, Gschwantler-Kaulich D, Dressler C, Fink A, Szabo CI, Zikan M, Foretova L, Claes K, Thomas G, Hoover RN, Hunter DJ, Chanock SJ, Easton DF, Antoniou AC, Couch FJ
- Issue date: 2010 Jul 15
- Breast cancer risk among male BRCA1 and BRCA2 mutation carriers.
- Authors: Tai YC, Domchek S, Parmigiani G, Chen S
- Issue date: 2007 Dec 5