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

作者：Fredrik Wiklund, Elio Ríboli, Manuel Luedeke, Wayne D. Tilley, Michael B. Cook, Rick A. Kittles, Nora Pashayan, Johanna Schleutker, C. Turman, A. Michael, Javier Llorca, Lisa Cannon‐Albright, Ruth C. Travis, Jung‐Eun Lim, J.Y. Park, Daniel W. Lin, William B. Isaacs, Stephen N. Thibodeau, Graham G. Giles, Robert J. Hamilton, James L. Mohler, Laurent Brureau, Timothy J. Key, Soo‐Hwang Teo, Stephen J. Chanock, John D. Carpten, Csilla Sipeky, Laura E. Beane Freeman, Craig C. Teerlink, Freddie C. Hamdy, Eli Marie Grindedal, Yves Akoli Koudou, Marija Gamulin, Catharine West, Cezary Cybulski, Paul A. Townsend, Bettina F. Drake, Lovise Mæhle, Jennifer Cullen, Robin J. Leach, Sara S. Strom, Gerald L. Andriole, James E. Mensah, Katarina Ćuk, Esther M. John, Manuela Gago-Domínguez, Janet L. Stanford, Hermann Brenner, Stella Koutros, Jenny Donovan, Ninghan Feng, Monique J. Roobol, David J. Hunter, Thérèse Truong, Sara Lindström, Samantha Larkin, Martin Eklund, Graham Casey, Andreia Brandão, Stig E. Bojesen, Judith A. Clements, Masashi Fujita, Lilit C. Moss, Ana Vega, Steven Joniau, Zsofia Kote‐Jarai, Tobias Nordström, Peter Iversen, J. Kim, Stephen Watya, Antonio Gómez‐Caamaño, Thomas Van den Broeck, Maya Ghoussaini, N. Mancuso, P. Wan, William J. Blot, Hongwei Zhang, Barry S. Rosenstein, Marı́a Elena Martı́nez, Robert Szulkin, Michael Borre, Hardev Pandha, Ann W. Hsing, Lisa G. Horvath, Kenneth Muir, Anselm Hennis, Manolis Kogevinas, Hidewaki Nakagawa, Rosalind A. Eeles, Yuan Chun Ding, Susan L. Neuhausen, Ian M. Thompson, Lynne R. Wilkens, Susan M. Gapstur, Robert J. MacInnis, Alison M. Dunning, Douglas F. Easton, Jianfeng Xu, Gert De Meerleer, Melissa C. Southey, María Torres, Kathryn L. Penney, Lisa F. Newcomb, Shannon K. McDonnell, Daniel J. Schaid, Marie‐Élise Parent, Jack A. Taylor, Peter Kraft, Christine Neslund‐Dudas, Elaine A. Ostrander, Phyllis J. Goodman, Chad D. Huff, Frank Claessens, Luc Multigner, Niclas Håkansson, N.G. Burnet, Sune F. Nielsen, Claire Aukim-Hastie, Chavdar Slavov, Olivier Cussenot, F. Ménégaux, Edward Giovannucci, Sandeep K. Singhal, David E. Neal, Melinda C. Aldrich, Antonio Finelli, Koichi Matsuda, Tokhir Dadaev, Tomislav Kuliš, Jose E. Castelao, Markus Aly, X. Sheng, Karina D. Sørensen, Eric A. Klein, Manuel R. Teixeira, Matthew Parliament, Nawaid Usmani, Alicja Wolk, Børge G. Nordestgaard, Shi Zhao, Ali Sahimi, Fredrick R. Schumacher, Linda Steele, Elizabeth T. H. Fontham, Laura Fachal, Stephen K. Van Den Eeden, Jennifer J. Hu, Wei Zheng, Jyotsna Batra, Leire Moya, Thomas J. Hoffmann, Ali Amin Al Olama, Alex Lubwama, Gail P. Risbridger, C. Maier, Loı̈c Le Marchand, Yukihide Momozawa, Harry Ostrer, John S. Witte, Roberta McKean‐Cowdin, Victoria L. Stevens, Yonghui Wu, Christopher J. Logothetis, Catherine M. Tangen, Azad Hassan Abdul Razack, Piet Ost, Sonja I. Berndt, Anssi Auvinen, Brad Carter, Hui‐Yi Lin, Géraldine Cancel‐Tassin, Lorelei A. Mucci, Dana C. Crawford, Teuvo L.J. Tammela, Zhongquan Sun, Jan Lubiński, William S. Bush, Adam S. Kibel, Demetrius Albanes, Davor Lessel, Shiv Srivastava, Benjamin A. Rybicki, Gill Barnett, Kim De Ruyck, Milan S. Geybels, Gemma Castaño‐Vinyals, Vanio Mitev, Edward J. Saunders, Richard M. Martin, Sue A. Ingles, Jay H. Fowke, Stephanie J. Weinstein, Neil E. Fleshner, Radka Kaneva, P. Blanchet, Mitchell J. Machiela, Dominika Wokołorczyk, K.-U. Saum, Mark N. Brook, Alisha Chou, Meir J. Stampfer, Ron H. N. van Schaik, György Petrovics, Brandi Weaver, Maren Weischer, David V. Conti, Sarah L. Kerns, Mariana C. Stern, B.F. Darst, Rohit Varma, Adam B. Murphy, Paula Paulo, Kay‐Tee Khaw, Maureen Sanderson, Bernd Holleczek, Martin Andreas Røder, Robert N. Hoover, Jeannette T. Bensen, Yong‐Jie Lu, Atsushi Takahashi, Sara Benlloch, C.A. Haiman, Thomas A. Sellers, Guido Jenster, Henrik Grönberg, Xueying Mao, Thomas Schnoeller, Edward D. Yeboah, Suzanne K. Chambers, Barbara Nemesure, Artitaya Lophatananon · 发表于：UNC Libraries · 年份：2023 · DOI：10.17615/3g7m-ta66 · 被引用次数：1 · 研究领域：Race, Genetics, and Society

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.