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

Publication Type:

Journal Article

Authors:

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

Source:

Human molecular genetics, Volume 22, Issue 2, p.408-15 (2013)

Keywords:

2013, Center-Authored Paper, November 2012, Public Health Sciences Division, Specimen Processing Core Facility

Abstract:

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.