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 ¼ 1.78; 95% confidence interval (CI), 1.25–2.52; P ¼ 0.001], as well as elevated risk of Gleason 8þ prostate cancer (HR ¼ 3.11; 95% CI, 1.63–5.95; P ¼ 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR ¼ 2.83; 95% CI, 1.71–4.68; P ¼ 0.00004) and elevated risk of Gleason 8þ prostate cancer (HR ¼ 4.95; 95% CI, 2.12–11.54; P ¼ 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.
Association of genomic domains in BRCA1 and BRCA2 with prostate cancer risk and aggressiveness / Patel, V. L.; Busch, E. L.; Friebel, T. M.; Cronin, A.; Leslie, G.; McGuffog, L.; Adlard, J.; Agata, S.; Agnarsson, B. A.; Ahmed, M.; Aittom, K.; Alducci, E.; Andrulis, I. L.; Arason, A.; Arnold, N.; Artioli, G.; Arver, B.; Auber, B.; Azzollini, J.; Balmana, 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.; Caldes, 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.; 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.; Diez, 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.; Feliubadalo, L.; Foretova, L.; Fostira, F.; Fountzilas, G.; Frost, D.; Garcia-Barberan, V.; Garre, P.; Gauthier-Villars, M.; Geczi, 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.; Izatt, L.; Jager, A.; James, P.; Janavicius, R.; Jensen, U. B.; Jensen, T. D.; Johannsson, O. Th.; 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-Fernandez, 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.; Perez-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.. - In: CANCER RESEARCH. - ISSN 0008-5472. - 80:3(2020), pp. 624-638. [10.1158/0008-5472.CAN-19-1840]
Association of genomic domains in BRCA1 and BRCA2 with prostate cancer risk and aggressiveness
Medici V.;Toss A.;
2020
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 ¼ 1.78; 95% confidence interval (CI), 1.25–2.52; P ¼ 0.001], as well as elevated risk of Gleason 8þ prostate cancer (HR ¼ 3.11; 95% CI, 1.63–5.95; P ¼ 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR ¼ 2.83; 95% CI, 1.71–4.68; P ¼ 0.00004) and elevated risk of Gleason 8þ prostate cancer (HR ¼ 4.95; 95% CI, 2.12–11.54; P ¼ 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.File | Dimensione | Formato | |
---|---|---|---|
VOR_Association of Genomic Domains in BRCA1 and BRCA2.pdf
Accesso riservato
Tipologia:
VOR - Versione pubblicata dall'editore
Dimensione
920.65 kB
Formato
Adobe PDF
|
920.65 kB | Adobe PDF | Visualizza/Apri Richiedi una copia |
POST_PRINT_0008-5472.can-19-1840.pdf
Open access
Tipologia:
AAM - Versione dell'autore revisionata e accettata per la pubblicazione
Dimensione
5.13 MB
Formato
Adobe PDF
|
5.13 MB | Adobe PDF | Visualizza/Apri |
Pubblicazioni consigliate
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris