• Clin Cancer Res · May 2008

    VDR and SRD5A2 polymorphisms combine to increase risk for prostate cancer in both non-Hispanic White and Hispanic White men.

    • Kathleen C Torkko, Adrie van Bokhoven, Phoung Mai, Joke Beuten, Ivana Balic, Tim E Byers, John E Hokanson, Jill M Norris, Anna E Barón, M Scott Lucia, Ian M Thompson, and Robin J Leach.
    • Department of Pathology, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado 80045, USA. Kathleen.torkko@ucdenver.edu
    • Clin Cancer Res. 2008 May 15; 14 (10): 3223-9.

    PurposeVitamin 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.Experimental DesignThis 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.ResultsUsing 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).ConclusionOur 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.

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