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

Authors:
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 L 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 Riboli Timothy J Key Gerald 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 Lubinski Stephen N Thibodeau Daniel J Schaid Karina D Sorensen Jyotsna Batra Judith A Clements Suzanne Chambers Joanne Aitken Robert A Gardiner Christiane Maier Walther Vogel Thilo Dörk Hermann Brenner Tomonori Habuchi Sue Ingles Esther M John Joanne L Dickinson Lisa Cannon-Albright Manuel R Teixeira Radka Kaneva Hong-Wei Zhang Yong-Jie Lu Jong Y Park Kathleen A Cooney Kenneth R Muir Daniel A Leongamornlert Edward Saunders Malgorzata Tymrakiewicz Nadiya Mahmud Michelle Guy Koveela Govindasami Lynne T O'Brien Rosemary A Wilkinson Amanda L Hall Emma J Sawyer Tokhir Dadaev Jonathan Morrison David P Dearnaley Alan Horwich Robert A Huddart Vincent S Khoo Christopher C Parker Nicholas Van As Christopher J Woodhouse Alan Thompson Tim Dudderidge Chris Ogden Colin S Cooper Artitaya Lophatonanon Melissa C Southey John L Hopper Dallas English Jarmo Virtamo Loic Le Marchand Daniele Campa Rudolf Kaaks Sara Lindstrom W Ryan Diver Susan Gapstur Meredith Yeager Angela Cox Mariana C Stern Roman Corral Markus Aly William Isaacs Jan Adolfsson Jianfeng Xu S Lilly Zheng Tiina Wahlfors Kimmo Taari Paula Kujala Peter Klarskov Børge G Nordestgaard M Andreas Røder Ruth Frikke-Schmidt Stig E Bojesen Liesel M FitzGerald Suzanne Kolb Erika M Kwon Danielle M Karyadi Torben Falck Orntoft Michael Borre Antje Rinckleb Manuel Luedeke Kathleen Herkommer Andreas Meyer Jürgen Serth James R Marthick Briony Patterson Dominika Wokolorczyk Amanda Spurdle Felicity Lose Shannon K McDonnell Amit D Joshi Ahva Shahabi Pedro Pinto Joana Santos Ana Ray Thomas A Sellers Hui-Yi Lin Robert A Stephenson Craig Teerlink Heiko Muller Dietrich Rothenbacher Norihiko Tsuchiya Shintaro Narita Guang-Wen Cao Chavdar Slavov Vanio Mitev Stephen Chanock Henrik Gronberg Christopher A Haiman Peter Kraft Douglas F Easton Rosalind A Eeles

Hum Mol Genet 2013 Jan 12;22(2):408-15. Epub 2012 Oct 12.

Strangeways Laboratory, Centre for Cancer Genetic Epidemiology, Worts Causeway, Cambridge CB1 8RN, UK.

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.

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January 2013
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