Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness

V.L. Patel, E.L. Busch, T.M. Friebel, A. Cronin, G. Leslie, L. McGuffog, J. Adlard, S. Agata, B.A. Agnarsson, M. Ahmed, K. Aittomäki, E. Alducci, I.L. Andrulis, A. Arason, N. Arnold, G. Artioli, B. Arver, B. Auber, J. Azzollini, J. BalmañaR.B. Barkardottir, D.R. Barnes, A. Barroso, D. Barrowdale, M. Belotti, J. Benitez, B. Bertelsen, M.J. Blok, I. Bodrogi, V. Bonadona, B. Bonanni, D. Bondavalli, S.E. Boonen, J. Borde, A. Borg, A.R. Bradbury, A. Brady, C. Brewer, J. Brunet, B. Buecher, S.S. Buys, S. Cabezas-Camarero, T. Caldés, A. Caliebe, M.A. Caligo, M. Calvello, I.G. Campbell, I. Carnevali, E. Carrasco, T.L. Chan, A.T.W. Chu, W.K. Chung, K.B.M. Claes, G.S. Collaborators, E. Collaborators, J. Cook, L. Cortesi, F.J. Couch, M.B. Daly, G. Damante, E. Darder, R. Davidson, M. de la Hoya, L.D. Puppa, J. Dennis, O. Díez, Y.C. Ding, N. Ditsch, S.M. Domchek, A. Donaldson, B. Dworniczak, D.F. Easton, D.M. Eccles, R.A. Eeles, H. Ehrencrona, B. Ejlertsen, C. Engel, D.G. Evans, L. Faivre, U. Faust, L. Feliubadaló, L. Foretova, F. Fostira, G. Fountzilas, D. Frost, V. García-Barberán, P. Garre, M. Gauthier-Villars, L. Géczi, A. Gehrig, A.-M. Gerdes, P. Gesta, G. Giannini, G. Glendon, A.K. Godwin, D.E. Goldgar, M.H. Greene, A.M. Gutierrez-Barrera, E. Hahnen, U. Hamann, J. Hauke, N. Herold, F.B.L. Hogervorst, E. Honisch, J.L. Hopper, P.J. Hulick, K. Investigators, H. Investigators, L. Izatt, A. Jager, P. James, R. Janavicius, U.B. Jensen, T.D. Jensen, O.T. Johannsson, E.M. John, V. Joseph, E. Kang, K. Kast, J.I. Kiiski, S.-W. Kim, Z. Kim, K.-P. Ko, I. Konstantopoulou, G. Kramer, L. Krogh, T.A. Kruse, A. Kwong, M. Larsen, C. Lasset, C. Lautrup, C. Lazaro, J. Lee, J.W. Lee, M.H. Lee, J. Lemke, F. Lesueur, A. Liljegren, A. Lindblom, P. Llovet, A. Lopez-Fernández, I. Lopez-Perolio, V. Lorca, J.T. Loud, E.S.K. Ma, P.L. Mai, S. Manoukian, V. Mari, L. Martin, L. Matricardi, N. Mebirouk, V. Medici, H.E.J. Meijers-Heijboer, A. Meindl, A.R. Mensenkamp, C. Miller, D.M. Gomes, M. Montagna, T.M. Mooij, L. Moserle, E. Mouret-Fourme, A.M. Mulligan, K.L. Nathanson, M. Navratilova, H. Nevanlinna, D. Niederacher, F.C.C. Nielsen, L. Nikitina-Zake, K. Offit, E. Olah, O.I. Olopade, K.-R. Ong, A. Osorio, C.-E. Ott, D. Palli, S.K. Park, M.T. Parsons, I.S. Pedersen, B. Peissel, A. Peixoto, P. Pérez-Segura, P. Peterlongo, A.H. Petersen, M.E. Porteous, M.A. Pujana, P. Radice, J. Ramser, J. Rantala, M.U. Rashid, K. Rhiem, P. Rizzolo, M.E. Robson, M.A. Rookus, C.M. Rossing, K.J. Ruddy, C. Santos, C. Saule, R. Scarpitta, R.K. Schmutzler, H. Schuster, L. Senter, C.M. Seynaeve, P.D. Shah, P. Sharma, V.Y. Shin, V. Silvestri, J. Simard, C.F. Singer, A.-B. Skytte, K. Snape, A.R. Solano, P. Soucy, M.C. Southey, A.B. Spurdle, L. Steele, D. Steinemann, D. Stoppa-Lyonnet, A. Stradella, L. Sunde, C. Sutter, Y.Y. Tan, M.R. Teixeira, S.H. Teo, M. Thomassen, M.G. Tibiletti, M. Tischkowitz, S. Tognazzo, A.E. Toland, S. Tommasi, D. Torres, A. Toss, A.H. Trainer, N. Tung, C.J. van Asperen, F.H. van der Baan, L.E. van der Kolk, R.B. van der Luijt, L.P. van Hest, L. Varesco, R. Varon-Mateeva, A. Viel, J. Vierstrate, R. Villa, A. von Wachenfeldt, P. Wagner, S. Wang-Gohrke, B. Wappenschmidt, J.N. Weitzel, G. Wieme, S. Yadav, D. Yannoukakos, S.-Y. Yoon, C. Zanzottera, K.K. Zorn, A.V. D'Amico, M.L. Freedman, M.M. Pomerantz, G. Chenevix-Trench, A.C. Antoniou, S.L. Neuhausen, L. Ottini, H.R. Nielsen, T.R. Rebbeck

Research output: Contribution to journalArticlepeer-review

Abstract

Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 3' region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001-c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25-2.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63-5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71-4.68; P = 0.00004) and elevated risk of Gleason 8+ prostate cancer (HR = 4.95; 95% CI, 2.12-11.54; P = 0.0002). No genotype-phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. SIGNIFICANCE: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual. ©2019 American Association for Cancer Research.
Original languageEnglish
Pages (from-to)624-638
Number of pages15
JournalCancer Research
Volume80
Issue number3
Early online dateNov 13 2019
DOIs
Publication statusPublished - Feb 1 2020

Fingerprint Dive into the research topics of 'Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness'. Together they form a unique fingerprint.

Cite this