학술논문
Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
Document Type
Article
Author
Conti, David V.; Darst, Burcu F.; Moss, Lilit C.; Saunders, Edward J.; Sheng, Xin; Chou, Alisha; Schumacher, Fredrick R.; Olama, Ali Amin Al; Benlloch, Sara; Dadaev, Tokhir; Brook, Mark N.; Sahimi, Ali; Hoffmann, Thomas J.; Takahashi, Atushi; Matsuda, Koichi; Momozawa, Yukihide; Fujita, Masashi; Muir, Kenneth; Lophatananon, Artitaya; Wan, Peggy; Le Marchand, Loic; Wilkens, Lynne R.; Stevens, Victoria L.; Gapstur, Susan M.; Carter, Brian D.; Schleutker, Johanna; Tammela, Teuvo L. J.; Sipeky, Csilla; Auvinen, Anssi; Giles, Graham G.; Southey, Melissa C.; MacInnis, Robert J.; Cybulski, Cezary; Wokolorczyk, Dominika; Lubinski, Jan; Neal, David E.; Donovan, Jenny L.; Hamdy, Freddie C.; Martin, Richard M.; Nordestgaard, Børge G.; Nielsen, Sune F.; Weischer, Maren; Bojesen, Stig E.; Røder, Martin Andreas; Iversen, Peter; Batra, Jyotsna; Chambers, Suzanne; Moya, Leire; Horvath, Lisa; Clements, Judith A.; Tilley, Wayne; Risbridger, Gail P.; Gronberg, Henrik; Aly, Markus; Szulkin, Robert; Eklund, Martin; Nordström, Tobias; Pashayan, Nora; Dunning, Alison M.; Ghoussaini, Maya; Travis, Ruth C.; Key, Tim J.; Riboli, Elio; Park, Jong Y.; Sellers, Thomas A.; Lin, Hui-Yi; Albanes, Demetrius; Weinstein, Stephanie J.; Mucci, Lorelei A.; Giovannucci, Edward; Lindstrom, Sara; Kraft, Peter; Hunter, David J.; Penney, Kathryn L.; Turman, Constance; Tangen, Catherine M.; Goodman, Phyllis J.; Thompson, Ian M.; Hamilton, Robert J.; Fleshner, Neil E.; Finelli, Antonio; Parent, Marie-Élise; Stanford, Janet L.; Ostrander, Elaine A.; Geybels, Milan S.; Koutros, Stella; Freeman, Laura E. Beane; Stampfer, Meir; Wolk, Alicja; Håkansson, Niclas; Andriole, Gerald L.; Hoover, Robert N.; Machiela, Mitchell J.; Sørensen, Karina Dalsgaard; Borre, Michael; Blot, William J.; Zheng, Wei; Yeboah, Edward D.; Mensah, James E.; Lu, Yong-Jie; Zhang, Hong-Wei; Feng, Ninghan; Mao, Xueying; Wu, Yudong; Zhao, Shan-Chao; Sun, Zan; Thibodeau, Stephen N.; McDonnell, Shannon K.; Schaid, Daniel J.; West, Catharine M. L.; Burnet, Neil; Barnett, Gill; Maier, Christiane; Schnoeller, Thomas; Luedeke, Manuel; Kibel, Adam S.; Drake, Bettina F.; Cussenot, Olivier; Cancel-Tassin, Géraldine; Menegaux, Florence; Truong, Thérèse; Koudou, Yves Akoli; John, Esther M.; Grindedal, Eli Marie; Maehle, Lovise; Khaw, Kay-Tee; Ingles, Sue A.; Stern, Mariana C.; Vega, Ana; Gómez-Caamaño, Antonio; Fachal, Laura; Rosenstein, Barry S.; Kerns, Sarah L.; Ostrer, Harry; Teixeira, Manuel R.; Paulo, Paula; Brandão, Andreia; Watya, Stephen; Lubwama, Alexander; Bensen, Jeannette T.; Fontham, Elizabeth T. H.; Mohler, James; Taylor, Jack A.; Kogevinas, Manolis; Llorca, Javier; Castaño-Vinyals, Gemma; Cannon-Albright, Lisa; Teerlink, Craig C.; Huff, Chad D.; Strom, Sara S.; Multigner, Luc; Blanchet, Pascal; Brureau, Laurent; Kaneva, Radka; Slavov, Chavdar; Mitev, Vanio; Leach, Robin J.; Weaver, Brandi; Brenner, Hermann; Cuk, Katarina; Holleczek, Bernd; Saum, Kai-Uwe; Klein, Eric A.; Hsing, Ann W.; Kittles, Rick A.; Murphy, Adam B.; Logothetis, Christopher J.; Kim, Jeri; Neuhausen, Susan L.; Steele, Linda; Ding, Yuan Chun; Isaacs, William B.; Nemesure, Barbara; Hennis, Anselm J. M.; Carpten, John; Pandha, Hardev; Michael, Agnieszka; De Ruyck, Kim; De Meerleer, Gert; Ost, Piet; Xu, Jianfeng; Razack, Azad; Lim, Jasmine; Teo, Soo-Hwang; Newcomb, Lisa F.; Lin, Daniel W.; Fowke, Jay H.; Neslund-Dudas, Christine; Rybicki, Benjamin A.; Gamulin, Marija; Lessel, Davor; Kulis, Tomislav; Usmani, Nawaid; Singhal, Sandeep; Parliament, Matthew; Claessens, Frank; Joniau, Steven; Van den Broeck, Thomas; Gago-Dominguez, Manuela; Castelao, Jose Esteban; Martinez, Maria Elena; Larkin, Samantha; Townsend, Paul A.; Aukim-Hastie, Claire; Bush, William S.; Aldrich, Melinda C.; Crawford, Dana C.; Srivastava, Shiv; Cullen, Jennifer C.; Petrovics, Gyorgy; Casey, Graham; Roobol, Monique J.; Jenster, Guido; van Schaik, Ron H. N.; Hu, Jennifer J.; Sanderson, Maureen; Varma, Rohit; McKean-Cowdin, Roberta; Torres, Mina; Mancuso, Nicholas; Berndt, Sonja I.; Van Den Eeden, Stephen K.; Easton, Douglas F.; Chanock, Stephen J.; Cook, Michael B.; Wiklund, Fredrik; Nakagawa, Hidewaki; Witte, John S.; Eeles, Rosalind A.; Kote-Jarai, Zsofia; Haiman, Christopher A.
Source
Nature Genetics; January 2021, Vol. 53 Issue: 1 p65-75, 11p
Subject
Language
ISSN
10614036; 15461718
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.