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

2021; Nature Portfolio; Volume: 53; Issue: 1 Linguagem: Inglês

10.1038/s41588-020-00748-0

1546-1718

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

Prostate Cancer Treatment and Research

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. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.