Abstract for presentation at 11th International Congress of Human Genetics

Interactions between SRD5A2 V89L and VDR FokI Polymorphisms in Relation to Risk for Prostate Cancer

  • Kathleen Torkko, University of Colorado at Denver and Health Sciences Center, United States
  • Dr Adrie van Bokhoven, University of Colorado at Denver and Health Sciences Center, United States
  • Dr Ivana Balic, University of Texas Health Sciences Center, San Antonio, United States
  • Dr Robin Leach, University of Texas Health Sciences Center, San Antonio, United States
  • Dr TIm Byers, University of Colorado at Denver and Health Sciences Center, United States
  • Dr John Hokanson, University of Colorado at Denver and Health Sciences Center, United States
  • Dr Jill Norris, University of Colorado at Denver and Health Sciences Center, United States
  • Dr Anna Baron, University of Colorado at Denver and Health Sciences Center, United States
  • M, Scott Lucia, University of Colorado at Denver and Health Sciences Center, United States
  • Ian Thompson, Department of Urology, University of Texas Health Sciences Center, United States

    • Testosterone and dihydrotestosterone (DHT) are necessary for normal growth of the prostate and play a role in prostate cancer development. 5a-Reductase type II converts testosterone to DHT in the prostate. The L allele of the 5a-reductase type II gene (SRD5A2) V89L polymorphism reduces 5a-reductase activity resulting in lower DHT levels. Vitamin D and DHT pathways interact to promote normal growth and differentiation of prostatic tissue. This study tested interactions of vitamin D receptor (VDR) and SRD5A2 gene polymorphisms and risk for prostate cancer. Seven VDR polymorphisms (CDX2, FokI, BsmI, Tru9I, ApaI, TaqI, Poly-A) and the SRD5A2 V89L polymorphism were genotyped in a cohort of non-Hispanic White men (281 cases, 395 controls) from south Texas, USA. Cases had biopsy-confirmed prostate cancer, while controls had normal digital rectal exams and serum prostate specific antigen <2.5 ng/ml. Using age-adjusted logistic regression analyses, neither V89L (VV vs. LL/LV) nor FokI (TT/CT vs. CC) alone were associated with prostate cancer (V89L: OR=1.05, 95%CI: 0.77, 1.42; FokI: OR=1.29, 95%CI: 0.94, 1.77). When stratified by V89L genotype, FokI was associated with prostate cancer in men with the V89L VV genotype (OR=1.87, 95%CI: 1.19, 2.92). The interaction term in the full model was significant (p=0.02). A common haplotype was determined using standard linkage disequilibrium techniques (i.e., BsmI/Tru9I/ApaI/TaqI/Poly-A: GGCTL). This haplotype was estimated in individuals by creating a haplogenotype (i.e., men homozygous for all GGCTL alleles). The haplogenotype compared to all other genotype combinations was associated with reduced risk for prostate cancer (OR=0.61, 95%CI: 0.41, 0.91). The protective effect was increased in men with LL/LV genotypes (OR=0.44, 95%CI: 0.25, 0.78), although the interaction term did not reach significance. The SRD5A2 V89L VV genotype interacts with the VDR FokI TT/CT genotypes to increase risk for prostate cancer.

    Conference Organiser - ICMS Pty Ltd