title: An analysis of the association between prostate cancer risk loci, PSA levels, disease aggressiveness and disease-specific mortality.
abstract: BACKGROUND
  Genome-wide association studies have identified multiple single-nucleotide polymorphsims (SNPs) associated with prostate cancer (PCa). Although these SNPs have been clearly associated with disease risk, their relationship with clinical outcomes is less clear. Our aim was to assess the frequency of known PCa susceptibility alleles within a single institution ascertainment and to correlate risk alleles with disease-specific outcomes.
  
  
  METHODS
  We genotyped 1354 individuals treated for localised PCa between June 1988 and December 2007. Blood samples were prospectively collected and de-identified before being genotyped and matched to phenotypic data. We investigated associations between 61 SNPs and disease-specific end points using multivariable analysis and also determined if SNPs were associated with PSA at diagnosis.
  
  
  RESULTS
  Seven SNPs showed associations on multivariable analysis (P<0.05), rs13385191 with both biochemical recurrence (BR) and castrate metastasis (CM), rs339331 (BR), rs1894292, rs17178655 and rs11067228 (CM), and rs11902236 and rs4857841 PCa-specific mortality. After applying a Bonferroni correction for number of SNPs (P<0.0008), the only persistent significant association was between rs17632542 (KLK3) and PSA levels at diagnosis (P=1.4 × 10(-5)).
  
  
  CONCLUSIONS
  We confirmed that rs17632542 in KLK3 is associated with PSA at diagnosis. No significant association was seen between loci and disease-specific end points when accounting for multiple testing. This provides further evidence that known PCa risk SNPs do not predict likelihood of disease progression.
authors.affiliation: 1] Department of Medicine, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA [2] Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Sullivan
authors.affiliation: 1] Department of Medicine, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA [2] Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kopp
authors.affiliation: 1] Department of Medicine, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA [2] Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: K
authors.initials: K
authors.lastname: Stratton
authors.affiliation: Department of Medicine, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: C
authors.initials: C
authors.lastname: Manschreck
authors.affiliation: Department of Medicine, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Corines
authors.affiliation: Department of Medicine, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Rau-Murthy
authors.affiliation: Department of Medicine, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Hayes
authors.affiliation: Department of Medicine, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: A
authors.initials: A
authors.lastname: Lincon
authors.affiliation: Department of Medicine, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: A
authors.initials: A
authors.lastname: Ashraf
authors.affiliation: Department of Medicine, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: T
authors.initials: T
authors.lastname: Thomas
authors.affiliation: Department of Medicine, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: K
authors.initials: K
authors.lastname: Schrader
authors.affiliation: Department of Medicine, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: D
authors.initials: D
authors.lastname: Gallagher
authors.affiliation: Department of Medicine, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Hamilton
authors.affiliation: Department of Medicine, Genitourinary Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: H
authors.initials: H
authors.lastname: Scher
authors.affiliation: Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: H
authors.initials: H
authors.lastname: Lilja
authors.affiliation: Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: P
authors.initials: P
authors.lastname: Scardino
authors.affiliation: Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Eastham
authors.affiliation: Department of Medicine, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: K
authors.initials: K
authors.lastname: Offit
authors.affiliation: Department of Medicine, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Vijai
authors.affiliation: 1] Department of Medicine, Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA [2] Icahn Institute for Genomics and Multiscale Biology, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Klein
mesh_terms: D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality
chemical_list: D017430:Prostate-Specific Antigen