title: VDR and SRD5A2 polymorphisms combine to increase risk for prostate cancer in both non-Hispanic White and Hispanic White men.
abstract: OBJECTIVE
  Vitamin D and dihydrotestosterone pathways interact to promote the growth of prostatic tissue. The nuclear vitamin D receptor (VDR) moderates the actions of vitamin D. 5alpha-Reductase type II (SRD5A2) codes for the enzyme that converts testosterone to dihydrotestosterone in the prostate. This study tested the interactions of VDR (CDX2, FokI) and SRD5A2 (V89L, A49T) polymorphisms, and their associations with prostate cancer.
  
  
  METHODS
  This genetic association study included 932 non-Hispanic White (NHW) men and 414 Hispanic White (HW) men from South Texas. Cases had biopsy-confirmed cancer; controls had normal digital rectal exams and serum prostate-specific antigen levels of <2.5 ng/mL.
  
  
  RESULTS
  Using logistic regression analyses to test associations with prostate cancer, only the V89L polymorphism (VV genotype compared with LL/LV) in HW men was statistically significant [odds ratios (OR), 0.64; 95% confidence intervals (95% CI), 0.41-0.99]. The interaction terms for FokI and V89L in NHW men and CDX2 and V89L in HW men in the logistic model were significant (P = 0.02 and 0.03, respectively). When stratified by V89L genotype, the FokI polymorphism (TT/TC versus CC) was significantly associated with prostate cancer in NHW men with the V89L VV genotype (FokI OR, 1.53; 95% CI, 1.06-2.23). The CDX2 polymorphism (GG versus AG/AA) was significantly associated with prostate cancer only in HW men with the V89L VV genotype (CDX2 OR, 3.16; 95% CI, 1.39-7.19; interaction term P = 0.02).
  
  
  CONCLUSIONS
  Our results indicate that the SRD5A2 V89L VV genotype interacts with VDR FokI TT/CT genotypes in NHW men and VDR CDX2 GG genotypes in HW men to increase the risk for prostate cancer.
authors.affiliation: Department of Pathology, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado 80045, USA. Kathleen.torkko@ucdenver.edu
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Torkko
authors.forename: Adrie
authors.initials: A
authors.lastname: van Bokhoven
authors.forename: Phoung
authors.initials: P
authors.lastname: Mai
authors.forename: Joke
authors.initials: J
authors.lastname: Beuten
authors.forename: Ivana
authors.initials: I
authors.lastname: Balic
authors.forename: Tim E
authors.initials: TE
authors.lastname: Byers
authors.forename: John E
authors.initials: JE
authors.lastname: Hokanson
authors.forename: Jill M
authors.initials: JM
authors.lastname: Norris
authors.forename: Anna E
authors.initials: AE
authors.lastname: Barón
authors.forename: M Scott
authors.initials: MS
authors.lastname: Lucia
authors.forename: Ian M
authors.initials: IM
authors.lastname: Thompson
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Leach
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics*; D000368:Aged; D020022:Genetic Predisposition to Disease; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D018167:Receptors, Calcitriol; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase