title: Prostate cancer susceptibility variants confer increased risk of disease progression.
abstract: BACKGROUND
  Genome-wide association studies have identified numerous single nucleotide polymorphisms (SNP) associated with the risk of prostate cancer. Our objective was to determine whether these SNPs affect the progression of prostate cancer.
  
  
  METHODS
  We genotyped 26 SNPs previously associated with prostate cancer risk among 788 aggressive prostate cancer patients who were treated by radical prostatectomy or radiation therapy. Prostate cancer progression was defined as biochemical recurrence based on posttreatment prostate-specific antigen levels of >0.3 ng/mL for radical prostatectomy patients or a 2-ng/mL increase above the nadir for radiation therapy patients, initiation of hormone treatment, or metastases. We assessed the association between independent and combined SNPs and disease progression by Cox proportional hazards regression.
  
  
  RESULTS
  Five SNPs showed independent associations with prostate cancer progression (rs12621278, rs629242, rs9364554, rs4430796, and rs5945572) based on stepwise regression analysis. The strongest SNP was rs12621278 in the ITGA6 locus, which was associated with a 2.4-fold increased risk of progression (P = 0.0003). When considering the sum of risk alleles across these five SNPs, each additional allele was associated with a 29% increase in risk of progression (95% confidence interval, 1.12-1-47).
  
  
  CONCLUSIONS
  We found that five of the recently highlighted prostate cancer susceptibility loci also influence prostate cancer progression beyond the known clinicopathologic predictors. If confirmed, these genetic variants might help clarify which tumors are likely to progress and require more aggressive treatment in contrast to those that might not have substantial effects on morbidity or mortality.
  
  
  CONCLUSIONS
  Genetic susceptibility variants for prostate cancer development may also inform disease progression.
authors.affiliation: Epidemiology Program, Cancer Research Center of Hawai'i, University of Hawai'i, Honolulu, Hawaii, USA.
authors.forename: Iona
authors.initials: I
authors.lastname: Cheng
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Plummer
authors.forename: Christine
authors.initials: C
authors.lastname: Neslund-Dudas
authors.forename: Eric A
authors.initials: EA
authors.lastname: Klein
authors.forename: Graham
authors.initials: G
authors.lastname: Casey
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Rybicki
authors.forename: John S
authors.initials: JS
authors.lastname: Witte
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology / Q000601:surgery
chemical_list: D017430:Prostate-Specific Antigen