Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

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Authors
Barnes, D. R.
Silvestri, V.
Leslie, G.
McGuffog, L.
Dennis, J.
Yang, X.
Adlard, J.
Agnarsson, B. A.
Ahmed, M.
Aittomäki, K.
Journal
Journal of the National Cancer Institute
Type
Journal Article
Publisher
Oxford University Press
Rights
© The Author(s) 2021. Published by Oxford University Press.
BACKGROUND: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. METHODS: 483 BRCA1 and 1,318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were three versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen-receptor (ER) negative (PRSER-) or ER-positive (PRSER+) breast cancer risk. RESULTS: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07-1.83) for BRCA1 and 1.33 (95% CI?=?1.16-1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for both BRCA1 (OR?=?1.73, 95% CI?=?1.28-2.33) and BRCA2 (OR?=?1.60, 95% CI?=?1.34-1.91) carriers. The estimated breast cancer ORs were larger after adjusting for female relative breast cancer family history. By age 85?years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. CONCLUSIONS: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and to inform clinical management.
Citation
Barnes, D. R. and Silvestri, V. and Leslie, G. and McGuffog, L. and Dennis, J. and Yang, X. and Adlard, J. and Agnarsson, B. A. and Ahmed, M. and Aittomäki, K. and Andrulis, I. L. and Arason, A. and Arnold, N. and Auber, B. and Azzollini, J. and Balmaña, J. and Barkardottir, R. B. and Barrowdale, D. and Barwell, J. and Belotti, M. and Benitez, J. and Berthet, P. and Boonen, S. E. and Borg, Å. and Bozsik, A. and Brady, A. and Brennan, P. and Brewer, C. and Brunet, J. and Bucalo, A. and Buys, S. S. and Caldés, T. and Caligo, M. A. and Campbell, I. and Cassingham, H. and Lotte Christensen, L. and Cini, G. and Claes, K. B. M. and Cook, J. and Coppa, A. and Cortesi, L. and Damante, G. and Darder, E. and Davidson, R. and de la Hoya, M. and De Leeneer, K. and de Putter, R. and Del Valle, J. and Diez, O. and Chun Ding, Y. and Domchek, S. M. and Donaldson, A. and Eason, J. and Eeles, R. and Engel, C. and Gareth Evans, D. and Feliubadaló, L. and Fostira, F. and Frone, M. and Frost, D. and Gallagher, D. and Gehrig, A. and Giraud, S. and Glendon, G. and Godwin, A. K. and Goldgar, D. E. and Greene, M. H. and Gregory, H. and Gross, E. and Hahnen, E. and Hamann, U. and Hansen, T. V. O. and Hanson, H. and Hentschel, J. and Horvath, J. and Izatt, L. and Izquierdo, A. and James, P. A. and Janavicius, R. and Birk Jensen, U. and Johannsson, O. T. and John, E. M. and Kramer, G. and Kroeldrup, L. and Kruse, T. A. and Lautrup, C. and Lazaro, C. and Lesueur, F. and Lopez-Fernández, A. and Mai, P. L. and Manoukian, S. and Matrai, Z. and Matricardi, L. and Maxwell, K. N. and Mebirouk, N. and Meindl, A. and Montagna, M. and Monteiro, A. N. and Morrison, P. J. and Muranen, T. A. and Murray, A. and Nathanson, K. L. and Neuhausen, S. L. and Nevanlinna, H. and Nguyen-Dumont, T. and Niederacher, D. and Olah, E. and Olopade, O. I. and Palli, D. and Parsons, M. T. and Sokilde Pedersen, I. and Peissel, B. and Perez-Segura, P. and Peterlongo, P. and Petersen, A. H. and Pinto, P. and Porteous, M. E. and Pottinger, C. and Angel Pujana, M. and Radice, P. and Ramser, J. and Rantala, J. and Robson, M. and Rogers, M. T. and Rønlund, K. and Rump, A. and María Sánchez de Abajo, A. and Shah, P. D. and Sharif, S. and Side, L. E. and Singer, C. F. and Stadler, Z. and Steele, L. and Stoppa-Lyonnet, D. and Sutter, C. and Yen Tan, Y. and Teixeira, M. R. and Teulé, A. and Thull, D. L. and Tischkowitz, M. and Toland, A. E. and Tommasi, S. and Toss, A. and Trainer, A. H. and Tripathi, V. and Valentini, V. and van Asperen, C. J. and Venturelli, M. and Viel, A. and Vijai, J. and Walker, L. and Wang-Gohrke, S. and Wappenschmidt, B. and Whaite, A. and Zanna, I. and Offit, K. and Thomassen, M. and Couch, F. J. and Schmutzler, R. K. and Simard, J. and Easton, D. F. and Chenevix-Trench, G. and Antoniou, A. C. and Ottini, L. (2021) 'Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores', Journal of the National Cancer Institute.
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