Association of Genomic Domains in <i>BRCA1</i> and <i>BRCA2</i> with Prostate Cancer Risk and Aggressiveness.

Patel, VL; Busch, EL; Friebel, TM; Cronin, A; Leslie, G; McGuffog, L; Adlard, J; Agata, S; Agnarsson, BA; Ahmed, M; Aittomäki, K; Alducci, E; Andrulis, IL; Arason, A; Arnold, N; Artioli, G; Arver, B; Auber, B; Azzollini, J; Balmaña, J; Barkardottir, RB; Barnes, DR; Barroso, A; Barrowdale, D; Belotti, M; Benitez, J; Bertelsen, B; Blok, MJ; Bodrogi, I; Bonadona, V; Bonanni, B; Bondavalli, D; Boonen, SE; Borde, J; Borg, A; Bradbury, AR; Brady, A; Brewer, C; Brunet, J; Buecher, B; Buys, SS; Cabezas-Camarero, S; Caldés, T; Caliebe, A; Caligo, MA; Calvello, M; Campbell, IG; Carnevali, I; Carrasco, E; Chan, TL; Chu, ATW; Chung, WK; Claes, KBM; Collaborators, GS; Collaborators, E; Cook, J; Cortesi, L; Couch, FJ; Daly, MB; Damante, G; Darder, E; Davidson, R; de la Hoya, M; Puppa, LD; Dennis, J; Díez, O; Ding, YC; Ditsch, N; Domchek, SM; Donaldson, A; Dworniczak, B; Easton, DF; Eccles, DM; Eeles, RA; Ehrencrona, H; Ejlertsen, B; Engel, C; Evans, DG; 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, AK; Goldgar, DE; Greene, MH; Gutierrez-Barrera, AM; Hahnen, E; Hamann, U; Hauke, J; Herold, N; Hogervorst, FBL; Honisch, E; Hopper, JL; Hulick, PJ; Investigators, K; Investigators, H; Izatt, L; Jager, A; James, P; Janavicius, R; Jensen, UB; Jensen, TD; Johannsson, OT; John, EM; Joseph, V; Kang, E; Kast, K; Kiiski, JI; Kim, S-W; Kim, Z; Ko, K-P; Konstantopoulou, I; Kramer, G; Krogh, L; Kruse, TA; Kwong, A; Larsen, M; Lasset, C; Lautrup, C; Lazaro, C; Lee, J; Lee, JW; Lee, MH; Lemke, J; Lesueur, F; Liljegren, A; Lindblom, A; Llovet, P; Lopez-Fernández, A; Lopez-Perolio, I; Lorca, V; Loud, JT; Ma, ESK; Mai, PL; Manoukian, S; Mari, V; Martin, L; Matricardi, L; Mebirouk, N; Medici, V; Meijers-Heijboer, HEJ; Meindl, A; Mensenkamp, AR; Miller, C; Gomes, DM; Montagna, M; Mooij, TM; Moserle, L; Mouret-Fourme, E; Mulligan, AM; Nathanson, KL; Navratilova, M; Nevanlinna, H; Niederacher, D; Nielsen, FCC; Nikitina-Zake, L; Offit, K; Olah, E; Olopade, OI; Ong, K-R; Osorio, A; Ott, C-E; Palli, D; Park, SK; Parsons, MT; Pedersen, IS; Peissel, B; Peixoto, A; Pérez-Segura, P; Peterlongo, P; Petersen, AH; Porteous, ME; Pujana, MA; Radice, P; Ramser, J; Rantala, J; Rashid, MU; Rhiem, K; Rizzolo, P; Robson, ME; Rookus, MA; Rossing, CM; Ruddy, KJ; Santos, C; Saule, C; Scarpitta, R; Schmutzler, RK; Schuster, H; Senter, L; Seynaeve, CM; Shah, PD; Sharma, P; Shin, VY; Silvestri, V; Simard, J; Singer, CF; Skytte, A-B; Snape, K; Solano, AR; Soucy, P; Southey, MC; Spurdle, AB; Steele, L; Steinemann, D; Stoppa-Lyonnet, D; Stradella, A; Sunde, L; Sutter, C; Tan, YY; Teixeira, MR; Teo, SH; Thomassen, M; Tibiletti, MG; Tischkowitz, M; Tognazzo, S; Toland, AE; Tommasi, S; Torres, D; Toss, A; Trainer, AH; Tung, N; van Asperen, CJ; van der Baan, FH; van der Kolk, LE; van der Luijt, RB; van Hest, LP; Varesco, L; Varon-Mateeva, R; Viel, A; Vierstraete, J; Villa, R; von Wachenfeldt, A; Wagner, P; Wang-Gohrke, S; Wappenschmidt, B; Weitzel, JN; Wieme, G; Yadav, S; Yannoukakos, D; Yoon, S-Y; Zanzottera, C; Zorn, KK; D'Amico, AV; Freedman, ML; Pomerantz, MM; Chenevix-Trench, G; Antoniou, AC; Neuhausen, SL; Ottini, L; Nielsen, HR; Rebbeck, TR

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Date

2020-02

ICR Author

Eeles, Rosalind

Author

Patel, VL

Busch, EL

Friebel, TM

Cronin, A

Leslie, G

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Type

Journal Article

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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.

URI

https://repository.icr.ac.uk/handle/internal/3505

DOI

https://doi.org/10.1158/0008-5472.can-19-1840

Collections

Subject

Humans

Prostatic Neoplasms

Genetic Predisposition to Disease

BRCA1 Protein

BRCA2 Protein

Prognosis

Risk Factors

Genomics

Heterozygote

Mutation

Adolescent

Adult

Aged

Aged, 80 and over

Middle Aged

Male

Young Adult

Genetic Association Studies

Research team

Oncogenetics

Language

eng

Date accepted

2019-11-08

License start date

2020-02

Citation

Cancer research, 2020, 80 (3), pp. 624 - 638

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