A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease.
Amin Al Olama A, Kote-Jarai Z, Schumacher FR, Wiklund F, Berndt SI, Benlloch S, Giles GG, Severi G, Neal DE, Hamdy FC, Donovan JL, Hunter DJ, Henderson BE, Thun MJ, Gaziano M, Giovannucci EL, Siddiq A, Travis RC, Cox DG, Canzian F, Riboli E, Key TJ, Andriole G, Albanes D, Hayes RB, Schleutker J, Auvinen A, Tammela TL, Weischer M, Stanford JL, Ostrander EA, Cybulski C, Lubinski J, Thibodeau SN, Schaid DJ, Sorensen KD, Batra J, Clements JA, Chambers S, Aitken J, Gardiner RA, Maier C, Vogel W, Dörk T, Brenner H, Habuchi T, Ingles S, John EM, Dickinson JL, Cannon-Albright L, Teixeira MR, Kaneva R, Zhang HW, Lu YJ, Park JY, Cooney KA, Muir KR, Leongamornlert DA, Saunders E, Tymrakiewicz M, Mahmud N, Guy M, Govindasami K, O'Brien LT, Wilkinson RA, Hall AL, Sawyer EJ, Dadaev T, Morrison J, Dearnaley DP, Horwich A, Huddart RA, Khoo VS, Parker CC, Van As N, Woodhouse CJ, Thompson A, Dudderidge T, Ogden C, Cooper CS, Lophatonanon A, Southey MC, Hopper JL, English D, Virtamo J, Le Marchand L, Campa D, Kaaks R, Lindstrom S, Diver WR, Gapstur S, Yeager M, Cox A, Stern MC, Corral R, Aly M, Isaacs W, Adolfsson J, Xu J, Zheng SL, Wahlfors T, Taari K, Kujala P, Klarskov P, Nordestgaard BG, Røder MA, Frikke-Schmidt R, Bojesen SE, FitzGerald LM, Kolb S, Kwon EM, Karyadi DM, Orntoft TF, Borre M, Rinckleb A, Luedeke M, Herkommer K, Meyer A, Serth J, Marthick JR, Patterson B, Wokolorczyk D, Spurdle A, Lose F, McDonnell SK, Joshi AD, Shahabi A, Pinto P, Santos J, Ray A, Sellers TA, Lin HY, Stephenson RA, Teerlink C, Muller H, Rothenbacher D, Tsuchiya N, Narita S, Cao GW, Slavov C, Mitev V, UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology, UK ProtecT Study Collaborators, Australian Prostate Cancer Bioresource, PRACTICAL Consortium, Chanock S, Gronberg H, Haiman CA, Kraft P, Easton DF, Eeles RA
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.