Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

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

View/Open

Published version (3.778Mb)

Publication Date

2021-01-04

ICR Author

Author

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

Type

Journal Article

Metadata

Show full item record

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.

URL

https://repository.icr.ac.uk/handle/internal/4768

Collections

Licenseref URL

https://www.rioxx.net/licenses/all-rights-reserved

Version

Version of record

10.1038/s41588-020-00748-0

Subject

Humans

Prostatic Neoplasms

Neoplasm Invasiveness

Genetic Predisposition to Disease

Odds Ratio

Risk Factors

Middle Aged

Continental Population Groups

Male

Genome-Wide Association Study

Genetic Loci

Molecular Sequence Annotation

Research team

Oncogenetics

Language

eng

Date accepted

2020-11-05

License start date

2021-01-04

Citation

Nature genetics, 2021, 53 (1), pp. 65 - 75

Publications Repository

Publications Repository