Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores.
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Date
2017-07-10ICR Author
Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Subject
EMBRACE
GEMO Study Collaborators
HEBON
KConFab Investigators
Humans
Breast Neoplasms, Male
Prostatic Neoplasms
Genetic Predisposition to Disease
Risk Assessment
Case-Control Studies
Age Factors
Heterozygote
Multifactorial Inheritance
Mutation
Polymorphism, Single Nucleotide
Genes, BRCA1
Genes, BRCA2
Adult
Aged
Aged, 80 and over
Middle Aged
Male
Genome-Wide Association Study
Genetic Testing
Research team
Complex Trait Genetics
Oncogenetics
Language
eng
Date accepted
2017-06-05
License start date
2017-07
Citation
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2017, 35 (20), pp. 2240 - 2250
Publisher
AMER SOC CLINICAL ONCOLOGY