Association of genomic domains in BRCA1 and BRCA2 with prostate cancer risk and aggressiveness Journal Article


Authors: Patel, V. L.; Busch, E. L.; Friebel, T. M.; Cronin, A.; Leslie, G.; McGuffog, L.; Adlard, J.; Agata, S.; Agnarsson, B. A.; Ahmed, M.; Aittomäki, K.; Alducci, E.; Andrulis, I. L.; Arason, A.; Arnold, N.; Artioli, G.; Arver, B.; Auber, B.; Azzollini, J.; Balmaña, J.; Barkardottir, R. B.; Barnes, D. R.; Barroso, A.; Barrowdale, D.; Belotti, M.; Benitez, J.; Bertelsen, B.; Blok, M. J.; Bodrogi, I.; Bonadona, V.; Bonanni, B.; Bondavalli, D.; Boonen, S. E.; Borde, J.; Borg, A.; Bradbury, A. R.; Brady, A.; Brewer, C.; Brunet, J.; Buecher, B.; Buys, S. S.; Cabezas-Camarero, S.; Caldés, T.; Caliebe, A.; Caligo, M. A.; Calvello, M.; Campbell, I. G.; Carnevali, I.; Carrasco, E.; Chan, T. L.; Chu, A. T. W.; Chung, W. K.; Claes, K. B. M.; GEMO Study Collaborators; EMBRACE Collaborators; Cook, J.; Cortesi, L.; Couch, F. J.; Daly, M. B.; Damante, G.; Darder, E.; Davidson, R.; de la Hoya, M.; Della Puppa, L.; Dennis, J.; Díez, O.; Ding, Y. C.; Ditsch, N.; Domchek, S. M.; Donaldson, A.; Dworniczak, B.; Easton, D. F.; Eccles, D. M.; Eeles, R. A.; Ehrencrona, H.; Ejlertsen, B.; Engel, C.; Evans, D. G.; Faivre, L.; Faust, U.; Feliubadaló, L.; Foretova, L.; Fostira, F.; Fountzilas, G.; Frost, D.; García-Barberán, V.; Garre, P.; Gauthier-Villars, M.; Géczi, L.; Gehrig, A.; Gerdes, A. M.; Gesta, P.; Giannini, G.; Glendon, G.; Godwin, A. K.; Goldgar, D. E.; Greene, M. H.; Gutierrez-Barrera, A. M.; Hahnen, E.; Hamann, U.; Hauke, J.; Herold, N.; Hogervorst, F. B. L.; Honisch, E.; Hopper, J. L.; Hulick, P. J.; KConFab Investigators; HEBON Investigators; Izatt, L.; Jager, A.; James, P.; Janavicius, R.; Jensen, U. B.; Jensen, T. D.; Johannsson, O. T.; John, E. M.; Joseph, V.; Kang, E.; Kast, K.; Kiiski, J. I.; Kim, S. W.; Kim, Z.; Ko, K. P.; Konstantopoulou, I.; Kramer, G.; Krogh, L.; Kruse, T. A.; Kwong, A.; Larsen, M.; Lasset, C.; Lautrup, C.; Lazaro, C.; Lee, J.; Lee, J. W.; Lee, M. H.; Lemke, J.; Lesueur, F.; Liljegren, A.; Lindblom, A.; Llovet, P.; Lopez-Fernández, A.; Lopez-Perolio, I.; Lorca, V.; Loud, J. T.; Ma, E. S. K.; Mai, P. L.; Manoukian, S.; Mari, V.; Martin, L.; Matricardi, L.; Mebirouk, N.; Medici, V.; Meijers-Heijboer, H. E. J.; Meindl, A.; Mensenkamp, A. R.; Miller, C.; Gomes, D. M.; Montagna, M.; Mooij, T. M.; Moserle, L.; Mouret-Fourme, E.; Mulligan, A. M.; Nathanson, K. L.; Navratilova, M.; Nevanlinna, H.; Niederacher, D.; Cilius Nielsen, F. C.; Nikitina-Zake, L.; Offit, K.; Olah, E.; Olopade, O. I.; Ong, K. R.; Osorio, A.; Ott, C. E.; Palli, D.; Park, S. K.; Parsons, M. T.; Pedersen, I. S.; Peissel, B.; Peixoto, A.; Pérez-Segura, P.; Peterlongo, P.; Petersen, A. H.; Porteous, M. E.; Pujana, M. A.; Radice, P.; Ramser, J.; Rantala, J.; Rashid, M. U.; Rhiem, K.; Rizzolo, P.; Robson, M. E.; Rookus, M. A.; Rossing, C. M.; Ruddy, K. J.; Santos, C.; Saule, C.; Scarpitta, R.; Schmutzler, R. K.; Schuster, H.; Senter, L.; Seynaeve, C. M.; Shah, P. D.; Sharma, P.; Shin, V. Y.; Silvestri, V.; Simard, J.; Singer, C. F.; Skytte, A. B.; Snape, K.; Solano, A. R.; Soucy, P.; Southey, M. C.; Spurdle, A. B.; Steele, L.; Steinemann, D.; Stoppa-Lyonnet, D.; Stradella, A.; Sunde, L.; Sutter, C.; Tan, Y. Y.; Teixeira, M. R.; Teo, S. H.; Thomassen, M.; Tibiletti, M. G.; Tischkowitz, M.; Tognazzo, S.; Toland, A. E.; Tommasi, S.; Torres, D.; Toss, A.; Trainer, A. H.; Tung, N.; van Asperen, C. J.; van der Baan, F. H.; van der Kolk, L. E.; van der Luijt, R. B.; van Hest, L. P.; Varesco, L.; Varon-Mateeva, R.; Viel, A.; Vierstrate, J.; Villa, R.; von Wachenfeldt, A.; Wagner, P.; Wang-Gohrke, S.; Wappenschmidt, B.; Weitzel, J. N.; Wieme, G.; Yadav, S.; Yannoukakos, D.; Yoon, S. Y.; Zanzottera, C.; Zorn, K. K.; D’Amico, A. V.; Freedman, M. L.; Pomerantz, M. M.; Chenevix-Trench, G.; Antoniou, A. C.; Neuhausen, S. L.; Ottini, L.; Nielsen, H. R.; Rebbeck, T. R.
Article Title: Association of genomic domains in BRCA1 and BRCA2 with prostate cancer risk and aggressiveness
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 8þ) 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 30 region of BRCA2 (c.7914þ) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001c.7913 [HR 1⁄4 1.78; 95% confidence interval (CI), 1.25–2.52; P 1⁄4 0.001], as well as elevated risk of Gleason 8þ prostate cancer (HR 1⁄4 3.11; 95% CI, 1.63–5.95; P 1⁄4 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR 1⁄4 2.83; 95% CI, 1.71–4.68; P 1⁄4 0.00004) and elevated risk of Gleason 8þ prostate cancer (HR 1⁄4 4.95; 95% CI, 2.12–11.54; P 1⁄4 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. © 2020 American Association for Cancer Research.
Journal Title: Cancer Research
Volume: 80
Issue: 3
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 2020-02-01
Start Page: 624
End Page: 638
Language: English
DOI: 10.1158/0008-5472.Can-19-1840
PUBMED: 31723001
PROVIDER: scopus
PMCID: PMC7553241
DOI/URL:
Notes: Article -- Export Date: 2 March 2020 -- Source: Scopus
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