Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness.
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ICR Authors
Authors
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
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
Document Type
Journal Article
Date
2020-02-01
Date Accepted
2019-11-08
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.
Citation
Cancer research, 2020, 80 (3), pp. 624 - 638
Source Title
Publisher
AMER ASSOC CANCER RESEARCH
ISSN
0008-5472
eISSN
1538-7445
Research Team
Oncogenetics