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

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 CanzianElio 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, Colin S Cooper, UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology

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103 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)408-415
Number of pages8
JournalHuman Molecular Genetics
Volume22
Issue number2
DOIs
Publication statusPublished - 15 Jan 2013

Keywords

  • Case-Control Studies
  • Disease Progression
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Male
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Prostatic Neoplasms
  • Quantitative Trait Loci
  • Reproducibility of Results

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