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VDR and SRD5A2 Polymorphisms Combine to Increase Risk for Prostate Cancer in Both Non–Hispanic White and Hispanic White Men

Authors' Affiliations: Departments of ¹ Pathology and ² Preventive Medicine and Biometrics, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado, Departments of ³ Cellular and Structural Biology, ⁴ Psychiatry, ⁵ Urology, and ⁶ Pediatrics, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas

Requests for reprints: Kathleen C. Torkko, Department of Pathology, University of Colorado Denver, Anschutz Medical Campus, Mail Stop 8104, P.O. Box 6511, Aurora, CO 80045. Phone: 303-724-3063; Fax: 303-724-3712; E-mail: Kathleen.torkko{at}ucdenver.edu.

Purpose: 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. 5-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 Design: 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).

Conclusion: 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.

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