title: Genetic variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes are prognostic markers of prostate cancer-specific mortality.
abstract: BACKGROUND
  Prostate cancer is the second leading cause of cancer-related deaths in men, accounting for more than 30,000 deaths annually. The purpose of this study was to test whether variation in selected candidate genes in biological pathways of interest for prostate cancer progression could help distinguish patients at higher risk for fatal prostate cancer.
  
  
  METHODS
  In this hypothesis-driven study, we genotyped 937 single nucleotide polymorphisms (SNPs) in 156 candidate genes in a population-based cohort of 1,309 prostate cancer patients. We identified 22 top-ranking SNPs (P ≤ 0.01, FDR ≤ 0.70) associated with prostate cancer-specific mortality (PCSM). A subsequent validation study was completed in an independent population-based cohort of 2,875 prostate cancer patients.
  
  
  RESULTS
  Five SNPs were validated (P ≤ 0.05) as being significantly associated with PCSM, one each in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes. Compared with patients with 0 to 2 of the at-risk genotypes those with 4 to 5 at-risk genotypes had a 50% (95% CI, 1.2-1.9) higher risk of PCSM and risk increased with the number of at-risk genotypes carried (P(trend) = 0.001), adjusting for clinicopathologic factors known to influence prognosis.
  
  
  CONCLUSIONS
  Five genetic markers were validated to be associated with lethal prostate cancer.
  
  
  CONCLUSIONS
  This is the first population-based study to show that germline genetic variants provide prognostic information for prostate cancer-specific survival. The clinical utility of this five-SNP panel to stratify patients at higher risk for adverse outcomes should be evaluated.
authors.affiliation: Department of Urology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Lin
authors.forename: Liesel M
authors.initials: LM
authors.lastname: FitzGerald
authors.forename: Rong
authors.initials: R
authors.lastname: Fu
authors.forename: Erika M
authors.initials: EM
authors.lastname: Kwon
authors.forename: Siqun Lilly
authors.initials: SL
authors.lastname: Zheng
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kolb
authors.forename: Fredrik
authors.initials: F
authors.lastname: Wiklund
authors.forename: Pär
authors.initials: P
authors.lastname: Stattin
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Ostrander
authors.forename: Ziding
authors.initials: Z
authors.lastname: Feng
authors.forename: Henrik
authors.initials: H
authors.lastname: Grönberg
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stanford
mesh_terms: D000328:Adult; D000368:Aged; D051186:Armadillo Domain Proteins / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D015331:Cohort Studies; D056931:Cryptochromes / Q000235:genetics*; D004722:Endoribonucleases / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality; D054411:Receptors, Leptin / Q000235:genetics*; D012307:Risk Factors
chemical_list: C411307:ARVCF protein, human; D051186:Armadillo Domain Proteins; C538963:CRY1 protein, human; D015815:Cell Adhesion Molecules; D056931:Cryptochromes; D010750:Phosphoproteins; D054411:Receptors, Leptin; D015847:Interleukin-4; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease