title: SRD5A2 and HSD3B2 polymorphisms are associated with prostate cancer risk and aggressiveness.
abstract: BACKGROUND
  Dihydrotestosterone (DHT) is believed to play an important role in prostate carcinogenesis. Five alpha reductase type II (SRD5A2) and 3 beta-hydroxysteroid dehydrogenase type II (HSD3B2) are responsible for the biosynthesis and degradation of DHT in the prostate. Two polymorphisms, a valine (V) for leucine (L) substitution at the 89 codon of the SRD5A2 gene and a (TG)n,(TA)n,(CA)n repeat polymorphism within the third intron of the HSD3B2 gene were evaluated with regard to prostate cancer risk.
  
  
  METHODS
  Blood samples were collected for 637 prostate cancer cases and 244 age and race frequency matched controls. In analysis, the SRD5A2 VL and LL genotypes were combined into one group and the HSD3B2 repeat polymorphism was dichotomized into short (<283) and long (> or =283) alleles.
  
  
  RESULTS
  The SRD5A2 V89L polymorphism was not independently associated with prostate cancer risk. Carriage of at least one HSD3B2 intron 3 intron 3 short allele was associated with a significant increased risk for prostate cancer among all subjects (OR = 2.07, 95% CI = 1.08-3.95, P = 0.03) and Caucasians (OR = 2.80, CI = 2.80-7.43, P = 0.04), but not in African Americans (OR = 1.50, CI = 0.62-3.60, P = 0.37). Stratified analyses revealed that most of the prostate cancer risk associated with the intron 3 HSD3B2 short allele was confined to the SRD5A2 89L variant subgroup and indicated that in combination these polymorphisms may be associated with increased risk of aggressive (Gleason >7) disease (Gleason >7).
  
  
  CONCLUSIONS
  In Caucasians, the HSD3B2 (TG)n,(TA)n,(CA)n intron 3 length polymorphism is associated with both prostate cancer risk and aggressiveness and the SRD5A2 V89L polymorphism may modify the risk conferred by this polymorphism.
authors.affiliation: Department of Biostatistics and Research Epidemiology, Henry Ford Hospital, Detroit, MI 48202, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Neslund-Dudas
authors.forename: Cathryn H
authors.initials: CH
authors.lastname: Bock
authors.forename: Kristin
authors.initials: K
authors.lastname: Monaghan
authors.forename: Nora L
authors.initials: NL
authors.lastname: Nock
authors.forename: James J
authors.initials: JJ
authors.lastname: Yang
authors.forename: Andrew
authors.initials: A
authors.lastname: Rundle
authors.forename: Deliang
authors.initials: D
authors.lastname: Tang
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Rybicki
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000097:blood / Q000235:genetics*; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics*; D000230:Adenocarcinoma / Q000097:blood / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D001741:Black or African American / Q000208:ethnology / Q000235:genetics; D000368:Aged; D004268:DNA-Binding Proteins / Q000097:blood / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008824:Michigan / Q000453:epidemiology; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011159:Population Surveillance; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000208:ethnology / Q000235:genetics