title: A genome-wide pleiotropy scan for prostate cancer risk.
abstract: BACKGROUND
  No single-nucleotide polymorphisms (SNPs) specific for aggressive prostate cancer have been identified in genome-wide association studies (GWAS).
  
  
  OBJECTIVE
  To test if SNPs associated with other traits may also affect the risk of aggressive prostate cancer.
  
  
  METHODS
  SNPs implicated in any phenotype other than prostate cancer (p≤10(-7)) were identified through the catalog of published GWAS and tested in 2891 aggressive prostate cancer cases and 4592 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). The 40 most significant SNPs were followed up in 4872 aggressive prostate cancer cases and 24,534 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.
  
  
  METHODS
  Odds ratios (ORs) and 95% confidence intervals (CIs) for aggressive prostate cancer were estimated.
  
  
  CONCLUSIONS
  A total of 4666 SNPs were evaluated by the BPC3. Two signals were seen in regions already reported for prostate cancer risk. rs7014346 at 8q24.21 was marginally associated with aggressive prostate cancer in the BPC3 trial (p=1.6×10(-6)), whereas after meta-analysis by PRACTICAL the summary OR was 1.21 (95% CI 1.16-1.27; p=3.22×10(-18)). rs9900242 at 17q24.3 was also marginally associated with aggressive disease in the meta-analysis (OR 0.90, 95% CI 0.86-0.94; p=2.5×10(-6)). Neither of these SNPs remained statistically significant when conditioning on correlated known prostate cancer SNPs. The meta-analysis by BPC3 and PRACTICAL identified a third promising signal, marked by rs16844874 at 2q34, independent of known prostate cancer loci (OR 1.12, 95% CI 1.06-1.19; p=4.67×10(-5)); it has been shown that SNPs correlated with this signal affect glycine concentrations. The main limitation is the heterogeneity in the definition of aggressive prostate cancer between BPC3 and PRACTICAL.
  
  
  CONCLUSIONS
  We did not identify new SNPs for aggressive prostate cancer. However, rs16844874 may provide preliminary genetic evidence on the role of the glycine pathway in prostate cancer etiology.
  
  
  RESULTS
  We evaluated whether genetic variants associated with several traits are linked to the risk of aggressive prostate cancer. No new such variants were identified.
authors.affiliation: Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
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authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Harvard University, Boston, MA, USA.
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authors.affiliation: Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, UK.
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authors.affiliation: Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
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authors.affiliation: Department of Epidemiology and Biostatistics, Imperial College School of Public Health, London, UK; Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands; Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, Netherlands; Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
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authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Harvard University, Boston, MA, USA; Hellenic Health Foundation, Athens, Greece; Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
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authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Department of Hygiene and Epidemiology, University of Ioannina, School of Medicine, Ioannina, Greece. Electronic address: kostas.tsilidis@ceu.ox.ac.uk.
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mesh_terms: D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D005998:Glycine / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics*; D012307:Risk Factors
chemical_list: D005998:Glycine
keywords: Aggressive prostate cancer; Genome-wide association study; Glycine; Pleiotropy; Single-nucleotide polymorphism