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

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Date
2020-02
ICR Author
Eeles, Rosalind
Author
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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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
  • Genetics and Epidemiology
  • Radiotherapy and Imaging
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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