Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.
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Authors
Conti, DV
Darst, BF
Moss, LC
Saunders, EJ
Sheng, X
Chou, A
Schumacher, FR
Olama, AAA
Benlloch, S
Dadaev, T
Brook, MN
Sahimi, A
Hoffmann, TJ
Takahashi, A
Matsuda, K
Momozawa, Y
Fujita, M
Muir, K
Lophatananon, A
Wan, P
Le Marchand, L
Wilkens, LR
Stevens, VL
Gapstur, SM
Carter, BD
Schleutker, J
Tammela, TLJ
Sipeky, C
Auvinen, A
Giles, GG
Southey, MC
MacInnis, RJ
Cybulski, C
Wokołorczyk, D
Lubiński, J
Neal, DE
Donovan, JL
Hamdy, FC
Martin, RM
Nordestgaard, BG
Nielsen, SF
Weischer, M
Bojesen, SE
Røder, MA
Iversen, P
Batra, J
Chambers, S
Moya, L
Horvath, L
Clements, JA
Tilley, W
Risbridger, GP
Gronberg, H
Aly, M
Szulkin, R
Eklund, M
Nordström, T
Pashayan, N
Dunning, AM
Ghoussaini, M
Travis, RC
Key, TJ
Riboli, E
Park, JY
Sellers, TA
Lin, H-Y
Albanes, D
Weinstein, SJ
Mucci, LA
Giovannucci, E
Lindstrom, S
Kraft, P
Hunter, DJ
Penney, KL
Turman, C
Tangen, CM
Goodman, PJ
Thompson, IM
Hamilton, RJ
Fleshner, NE
Finelli, A
Parent, M-É
Stanford, JL
Ostrander, EA
Geybels, MS
Koutros, S
Freeman, LEB
Stampfer, M
Wolk, A
Håkansson, N
Andriole, GL
Hoover, RN
Machiela, MJ
Sørensen, KD
Borre, M
Blot, WJ
Zheng, W
Yeboah, ED
Mensah, JE
Lu, Y-J
Zhang, H-W
Feng, N
Mao, X
Wu, Y
Zhao, S-C
Sun, Z
Thibodeau, SN
McDonnell, SK
Schaid, DJ
West, CML
Burnet, N
Barnett, G
Maier, C
Schnoeller, T
Luedeke, M
Kibel, AS
Drake, BF
Cussenot, O
Cancel-Tassin, G
Menegaux, F
Truong, T
Koudou, YA
John, EM
Grindedal, EM
Maehle, L
Khaw, K-T
Ingles, SA
Stern, MC
Vega, A
Gómez-Caamaño, A
Fachal, L
Rosenstein, BS
Kerns, SL
Ostrer, H
Teixeira, MR
Paulo, P
Brandão, A
Watya, S
Lubwama, A
Bensen, JT
Fontham, ETH
Mohler, J
Taylor, JA
Kogevinas, M
Llorca, J
Castaño-Vinyals, G
Cannon-Albright, L
Teerlink, CC
Huff, CD
Strom, SS
Multigner, L
Blanchet, P
Brureau, L
Kaneva, R
Slavov, C
Mitev, V
Leach, RJ
Weaver, B
Brenner, H
Cuk, K
Holleczek, B
Saum, K-U
Klein, EA
Hsing, AW
Kittles, RA
Murphy, AB
Logothetis, CJ
Kim, J
Neuhausen, SL
Steele, L
Ding, YC
Isaacs, WB
Nemesure, B
Hennis, AJM
Carpten, J
Pandha, H
Michael, A
De Ruyck, K
De Meerleer, G
Ost, P
Xu, J
Razack, A
Lim, J
Teo, S-H
Newcomb, LF
Lin, DW
Fowke, JH
Neslund-Dudas, C
Rybicki, BA
Gamulin, M
Lessel, D
Kulis, T
Usmani, N
Singhal, S
Parliament, M
Claessens, F
Joniau, S
Van den Broeck, T
Gago-Dominguez, M
Castelao, JE
Martinez, ME
Larkin, S
Townsend, PA
Aukim-Hastie, C
Bush, WS
Aldrich, MC
Crawford, DC
Srivastava, S
Cullen, JC
Petrovics, G
Casey, G
Roobol, MJ
Jenster, G
van Schaik, RHN
Hu, JJ
Sanderson, M
Varma, R
McKean-Cowdin, R
Torres, M
Mancuso, N
Berndt, SI
Van Den Eeden, SK
Easton, DF
Chanock, SJ
Cook, MB
Wiklund, F
Nakagawa, H
Witte, JS
Eeles, RA
Kote-Jarai, Z
Haiman, CA
Darst, BF
Moss, LC
Saunders, EJ
Sheng, X
Chou, A
Schumacher, FR
Olama, AAA
Benlloch, S
Dadaev, T
Brook, MN
Sahimi, A
Hoffmann, TJ
Takahashi, A
Matsuda, K
Momozawa, Y
Fujita, M
Muir, K
Lophatananon, A
Wan, P
Le Marchand, L
Wilkens, LR
Stevens, VL
Gapstur, SM
Carter, BD
Schleutker, J
Tammela, TLJ
Sipeky, C
Auvinen, A
Giles, GG
Southey, MC
MacInnis, RJ
Cybulski, C
Wokołorczyk, D
Lubiński, J
Neal, DE
Donovan, JL
Hamdy, FC
Martin, RM
Nordestgaard, BG
Nielsen, SF
Weischer, M
Bojesen, SE
Røder, MA
Iversen, P
Batra, J
Chambers, S
Moya, L
Horvath, L
Clements, JA
Tilley, W
Risbridger, GP
Gronberg, H
Aly, M
Szulkin, R
Eklund, M
Nordström, T
Pashayan, N
Dunning, AM
Ghoussaini, M
Travis, RC
Key, TJ
Riboli, E
Park, JY
Sellers, TA
Lin, H-Y
Albanes, D
Weinstein, SJ
Mucci, LA
Giovannucci, E
Lindstrom, S
Kraft, P
Hunter, DJ
Penney, KL
Turman, C
Tangen, CM
Goodman, PJ
Thompson, IM
Hamilton, RJ
Fleshner, NE
Finelli, A
Parent, M-É
Stanford, JL
Ostrander, EA
Geybels, MS
Koutros, S
Freeman, LEB
Stampfer, M
Wolk, A
Håkansson, N
Andriole, GL
Hoover, RN
Machiela, MJ
Sørensen, KD
Borre, M
Blot, WJ
Zheng, W
Yeboah, ED
Mensah, JE
Lu, Y-J
Zhang, H-W
Feng, N
Mao, X
Wu, Y
Zhao, S-C
Sun, Z
Thibodeau, SN
McDonnell, SK
Schaid, DJ
West, CML
Burnet, N
Barnett, G
Maier, C
Schnoeller, T
Luedeke, M
Kibel, AS
Drake, BF
Cussenot, O
Cancel-Tassin, G
Menegaux, F
Truong, T
Koudou, YA
John, EM
Grindedal, EM
Maehle, L
Khaw, K-T
Ingles, SA
Stern, MC
Vega, A
Gómez-Caamaño, A
Fachal, L
Rosenstein, BS
Kerns, SL
Ostrer, H
Teixeira, MR
Paulo, P
Brandão, A
Watya, S
Lubwama, A
Bensen, JT
Fontham, ETH
Mohler, J
Taylor, JA
Kogevinas, M
Llorca, J
Castaño-Vinyals, G
Cannon-Albright, L
Teerlink, CC
Huff, CD
Strom, SS
Multigner, L
Blanchet, P
Brureau, L
Kaneva, R
Slavov, C
Mitev, V
Leach, RJ
Weaver, B
Brenner, H
Cuk, K
Holleczek, B
Saum, K-U
Klein, EA
Hsing, AW
Kittles, RA
Murphy, AB
Logothetis, CJ
Kim, J
Neuhausen, SL
Steele, L
Ding, YC
Isaacs, WB
Nemesure, B
Hennis, AJM
Carpten, J
Pandha, H
Michael, A
De Ruyck, K
De Meerleer, G
Ost, P
Xu, J
Razack, A
Lim, J
Teo, S-H
Newcomb, LF
Lin, DW
Fowke, JH
Neslund-Dudas, C
Rybicki, BA
Gamulin, M
Lessel, D
Kulis, T
Usmani, N
Singhal, S
Parliament, M
Claessens, F
Joniau, S
Van den Broeck, T
Gago-Dominguez, M
Castelao, JE
Martinez, ME
Larkin, S
Townsend, PA
Aukim-Hastie, C
Bush, WS
Aldrich, MC
Crawford, DC
Srivastava, S
Cullen, JC
Petrovics, G
Casey, G
Roobol, MJ
Jenster, G
van Schaik, RHN
Hu, JJ
Sanderson, M
Varma, R
McKean-Cowdin, R
Torres, M
Mancuso, N
Berndt, SI
Van Den Eeden, SK
Easton, DF
Chanock, SJ
Cook, MB
Wiklund, F
Nakagawa, H
Witte, JS
Eeles, RA
Kote-Jarai, Z
Haiman, CA
Document Type
Journal Article
Date
2021-01-04
Date Accepted
2020-11-05
Abstract
Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.
Citation
Nature genetics, 2021, 53 (1), pp. 65 - 75
Source Title
Publisher
NATURE PORTFOLIO
ISSN
1061-4036
eISSN
1546-1718
Research Team
Oncogenetics
Oncogenetics
Oncogenetics