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A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease

2012; Oxford University Press; Volume: 22; Issue: 2 Linguagem: Inglês

10.1093/hmg/dds425

1460-2083

Ali Amin Al Olama, Zsofia Kote‐Jarai, Fredrick R. Schumacher, Fredrik Wiklund, Sonja I. Berndt, Sara Benlloch, Graham G. Giles, Gianluca Severi, David E. Neal, Freddie C. Hamdy, Jenny Donovan, David J. Hunter, Brian E. Henderson, Michael J. Thun, Michael Gaziano, Edward L. Giovannucci, Afshan Siddiq, Ruth C. Travis, David G. Cox, Federico Canzian, Elio Ríboli, Timothy J. Key, Gerald L. Andriole, Demetrius Albanes, Richard B. Hayes, Johanna Schleutker, Anssi Auvinen, Teuvo L.J. Tammela, Maren Weischer, Janet L. Stanford, Elaine A. Ostrander, Cezary Cybulski, Jan Lubiński, Stephen N. Thibodeau, Daniel J. Schaid, Karina D. Sørensen, Jyotsna Batra, Judith A. Clements, Suzanne K. Chambers, Joanne F. Aitken, Robert A. Gardiner, C. Maier, Walther Vogel, Thilo Dörk, Hermann Brenner, Tomonori Habuchi, Sue A. Ingles, Esther M. John, Joanne L. Dickinson, Lisa Cannon‐Albright, Manuel R. Teixeira, Radka Kaneva, H.-W. Zhang, Yong‐Jie Lu, J Y Park, Kathleen A. Cooney, Kenneth Muir, Daniel Leongamornlert, Edward J. Saunders, Malgorzata Tymrakiewicz, Nadiya Mahmud, Michelle Guy, Koveela Govindasami, Lynne T. O'Brien, Rosemary Wilkinson, Amanda L. Hall, Emma Sawyer, Tokhir Dadaev, Jean Morrison, David P. Dearnaley, Alan Horwich, Robert Huddart, Vincent Khoo, Chris Parker, Nicholas van As, Christopher Woodhouse, Alan Thompson, Tim Dudderidge, Chris Ogden, Christopher S. Cooper, Aritaya Lophatonanon, Melissa C. Southey, John L. Hopper, Dallas R. English, Jarmo Virtamo, Loı̈c Le Marchand, Daniele Campa, Rudolf Kaaks, Sara Lindström, W. Ryan Diver, Susan M. Gapstur, Meredith Yeager, Angela Cox, Marianna C. Stern, Román Corral, Markus Aly, William B. Isaacs, Jan Adolfsson, Jian Xu, S. Lilly Zheng, Tiina Wahlfors, Kimmo Taari, Paula Kujala, Peter Klarskov, Børge G. Nordestgaard, Martin Andreas Røder, Ruth Frikke‐Schmidt, Stig E. Bojesen, Liesel M. FitzGerald, Suzanne Kolb, Erika M. Kwon, Danielle M. Karyadi, Torben F. Ørntoft, Michael Borre, Antje E. Rinckleb, Manuel Luedeke, Kathleen Herkommer, Andreas Meyer, Jürgen Serth, James R. Marthick, Briony Patterson, Dominika Wokołorczyk, Amanda B. Spurdle, Felicity Lose, Shannon K. McDonnell, Amit D. Joshi, A Shahabi, Pedro Pinto, Joana Santos, Anna M. Ray, Thomas A. Sellers, Hui‐Yi Lin, Robert A. Stephenson, Craig C. Teerlink, Heiko Müller, Dietrich Rothenbacher, Norihiko Tsuchiya, Shintaro Narita, Guangwen Cao, Chavdar Slavov, Vanio Mitev, Stephen J. Chanock, Henrik Grönberg, C.A. Haiman, Peter Kraft, Douglas F. Easton, Rosalind A. Eeles,

Hormonal and reproductive studies

Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one-third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four GWAS including 5953 cases of aggressive PrCa and 11 463 controls (men without PrCa). We computed association tests for approximately 2.6 million SNPs and followed up the most significant SNPs by genotyping 49 121 samples in 29 studies through the international PRACTICAL and BPC3 consortia. We not only confirmed the association of a PrCa susceptibility locus, rs11672691 on chromosome 19, but also showed an association with aggressive PrCa [odds ratio = 1.12 (95% confidence interval 1.03–1.21), P = 1.4 × 10−8]. This report describes a genetic variant which is associated with aggressive PrCa, which is a type of PrCa associated with a poorer prognosis.