A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer

Ali Amin Al Olama, Zsofia Kote-Jarai, Sonja I. Berndt, David V. Conti, Fredrick Schumacher, Ying Han, Sara Benlloch, Dennis J. Hazelett, Zhaoming Wang, Ed Saunders, Daniel Leongamornlert, Sara Lindstrom, Sara Jugurnauth-Little, Tokhir Dadaev, Malgorzata Tymrakiewicz, Daniel O. Stram, Kristin Rand, Peggy Wan, Alex Stram, Xin ShengLoreall C. Pooler, Karen Park, Lucy Xia, Jonathan Tyrer, Laurence N. Kolonel, Loic Le Marchand, Robert N. Hoover, Mitchell J. Machiela, Merideth Yeager, Laurie Burdette, Charles C. Chung, Amy Hutchinson, Kai Yu, Chee Goh, Mahbubl Ahmed, Koveela Govindasami, Michelle Guy, Teuvo L.J. Tammela, Anssi Auvinen, Tiina Wahlfors, Johanna Schleutker, Tapio Visakorpi, Katri A. Leinonen, Jianfeng Xu, Markus Aly, Jenny Donovan, Ruth C. Travis, Tim J. Key, Afshan Siddiq, Federico Canzian, Kay Tee Khaw, Atsushi Takahashi, Michiaki Kubo, Paul Pharoah, Nora Pashayan, Maren Weischer, Borge G. Nordestgaard, Sune F. Nielsen, Peter Klarskov, Martin Andreas Røder, Peter Iversen, Stephen N. Thibodeau, Shannon K. McDonnell, Daniel J. Schaid, Janet L. Stanford, Suzanne Kolb, Sarah Holt, Beatrice Knudsen, Antonio Hurtado Coll, Susan M. Gapstur, W. Ryan Diver, Victoria L. Stevens, Christiane Maier, Manuel Luedeke, Kathleen Herkommer, Antje E. Rinckleb, Sara S. Strom, Curtis Pettaway, Edward D. Yeboah, Yao Tettey, Richard B. Biritwum, Andrew A. Adjei, Evelyn Tay, Ann Truelove, Shelley Niwa, Anand P. Chokkalingam, Lisa Cannon-Albright, Cezary Cybulski, Dominika Wokołorczyk, Wojciech Kluźniak, Jong Park, Thomas Sellers, Hui Yi Lin, William B. Isaacs, Alan W. Partin, Hermann Brenner, Aida Karina Dieffenbach, Christa Stegmaier, Constance Chen, Edward L. Giovannucci, Jing Ma, Meir Stampfer, Kathryn L. Penney, Lorelei Mucci, Esther M. John, Sue A. Ingles, Rick A. Kittles, Adam B. Murphy, Hardev Pandha, Agnieszka Michael, Andrzej M. Kierzek, William Blot, Lisa B. Signorello, Wei Zheng, Demetrius Albanes, Jarmo Virtamo, Stephanie Weinstein, Barbara Nemesure, John Carpten, Cristina Leske, Suh Yuh Wu, Anselm Hennis, Adam S. Kibel, Benjamin A. Rybicki, Christine Neslund-Dudas, Ann W. Hsing, Lisa Chu, Phyllis J. Goodman, Eric A. Klein, S. Lilly Zheng, Jyotsna Batra, Judith Clements, Amanda Spurdle, Manuel R. Teixeira, Paula Paulo, Sofia Maia, Chavdar Slavov, Radka Kaneva, Vanio Mitev, John S. Witte, Graham Casey, Elizabeth M. Gillanders, Daniella Seminara, Elio Riboli, Freddie C. Hamdy, Gerhard A. Coetzee, Qiyuan Li, Matthew L. Freedman, David J. Hunter, Kenneth Muir, Henrik Gronberg, David E. Neal, Melissa Southey, Graham G. Giles, Gianluca Severi, Michael B. Cook, Hidewaki Nakagawa, Fredrik Wiklund, Peter Kraft, Stephen J. Chanock, Brian E. Henderson, Douglas F. Easton, Rosalind A. Eeles, Christopher A. Haiman

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Abstract

Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of >10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10 â '8; 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.

Original languageEnglish
Pages (from-to)1103-1109
Number of pages7
JournalNature Genetics
Volume46
Issue number10
DOIs
Publication statusPublished - 26-09-2014

All Science Journal Classification (ASJC) codes

  • Genetics

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    Olama, A. A. A., Kote-Jarai, Z., Berndt, S. I., Conti, D. V., Schumacher, F., Han, Y., Benlloch, S., Hazelett, D. J., Wang, Z., Saunders, E., Leongamornlert, D., Lindstrom, S., Jugurnauth-Little, S., Dadaev, T., Tymrakiewicz, M., Stram, D. O., Rand, K., Wan, P., Stram, A., ... Haiman, C. A. (2014). A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. Nature Genetics, 46(10), 1103-1109. https://doi.org/10.1038/ng.3094