title: Prostate cancer predisposition loci and risk of metastatic disease and prostate cancer recurrence.
abstract: OBJECTIVE
  Genome-wide association studies (GWAS) have identified multiple novel prostate cancer predisposition loci. Whether these common genetic variants are associated with incident metastatic prostate cancer or with recurrence after surgical treatment for clinically localized prostate cancer is uncertain.
  
  
  METHODS
  Twelve single nucleotide polymorphisms (SNPs) were selected for study in relation to prostate metastatic cancer and recurrence, based on their genome-wide association with prostate cancer in the Cancer Genetic Markers of Susceptibility (CGEMS). To assess risk for metastatic disease, we compared genotypes for the 12 SNPs by logistic regression of 470 incident metastatic prostate cancer cases and 1,945 controls in 3 case-control studies. To assess the relationship of these SNPs to risk for prostate cancer recurrence, we used Cox regression in a cohort of 1,412 men treated for localized prostate cancer, including 328 recurrences, and used logistic regression in a case-case study, comparing 450 recurrent versus 450 nonrecurrent prostate cancer cases. Study-specific relative risks (RRs) for risk of metastatic disease and recurrence were summarized using meta-analysis, with inverse variance weights.
  
  
  RESULTS
  MSMB rs10993994 (per variant allele summary RR = 1.24, 95% CI = 1.05-1.48), 8q24 rs4242382 (RR = 1.40, 95% CI = 1.13-1.75), and 8q24 rs6983267 (RR = 0.67, 95% CI = 0.50-0.89) were associated with risk for metastatic prostate cancer. None of the 12 SNPs was associated with prostate cancer recurrence.
  
  
  CONCLUSIONS
  SNPs in MSMB and 8q24 which predispose to prostate cancer overall are associated with risk for metastatic prostate cancer, the most lethal form of this disease. SNPs predictive of prostate cancer recurrence were not identified, among the predisposition SNPs. GWAS specific to these 2 phenotypes may identify additional phenotype-specific genetic determinants.
authors.affiliation: Division of Epidemiology, Department of Environmental Medicine, NYU School of Medicine, New York, New York 10016, USA.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Ahn
authors.forename: Adam S
authors.initials: AS
authors.lastname: Kibel
authors.forename: Jong Y
authors.initials: JY
authors.lastname: Park
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
authors.forename: Hanna
authors.initials: H
authors.lastname: Rennert
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stanford
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Ostrander
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: Ming-Hsi
authors.initials: MH
authors.lastname: Wang
authors.forename: Rama D
authors.initials: RD
authors.lastname: Mittal
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Platz
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
mesh_terms: D000368:Aged; D000483:Alleles; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012306:Risk