Abstract for presentation at 11th International Congress of Human Genetics

Vitamin D Receptor Gene Haplotypes and Prostate Cancer in Hispanic and Non-Hispanic White Men

  • Kathleen Torkko, University of Colorado at Denver and Health Sciences Center, United States
  • Dr Phuong Mai, University of Texas Health Sciences Center, San Antonio, United States
  • Dr Robin Leach, University of Texas Health Sciences Center, San Antonio, United States
  • Ms Betsy Higgins, University of Texas Health Sciences Center, San Antonio, United States
  • Dr Adrie van Bokhoven, University of Colorado at Denver and Health Sciences Center, 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

    • The biologic activity of vitamin D, as mediated by the vitamin D receptor (VDR), may affect risk for prostate cancer. This case-control study examined the relationship between prostate cancer and a common VDR haplotype in two ethnic groups [non-Hispanic White (NHW), Hispanic White (HW)]. Seven polymorphisms (CDX2, FokI, BsmI, Tru9I, ApaI, TaqI, Poly-A repeat) were genotyped in 449 cases and 819 controls (69% NHW; 31% HW) 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. Standard linkage disequilibrium techniques identified a common haplotype (GGCTL) in the BsmI, Tru9I, ApaI, TaqI, and Poly-A repeat (dichotomized to Long/Short) polymorphisms. This haplotype was estimated in individuals by creating a haplogenotype (i.e., identifying men homozygous for all GGCTL alleles). Age-adjusted logistic regression analyses tested the association of prostate cancer with the haplogenotype compared to all other genotype combinations. The haplogenotype was inversely associated with prostate cancer among HW men (OR=0.49, 95%CI: 0.27, 0.89), but not in NHW men (OR=0.71, 95%CI: 0.50, 1.02; p=0.06). CDX2 acted as an effect modifier in NHW. The haplogenotype association became significant in NHW men with the CDX2 GG genotype (OR=0.57, 95%CI: 0.37, 0.87). There was no similar effect observed in HW men. The haplogenotype did not predict higher Gleason scores (grade 7-10) in either ethnic group. Analysis of individual polymorphisms found no significant associations in NHW men. HW men with the CDX2 GG genotype were at increased risk for prostate cancer (OR=1.81, 95%CI: 1.06, 3.08) and for higher Gleason scores (ordinal logistic regression comparing 7-10 to 2-6 to controls: OR=2.05, 95%CI: 1.11, 3.79). This study demonstrates that characterizing VDR haplotypes may add substantially to determining associations of VDR polymorphisms with prostate cancer, particularly in NHW men.

    Conference Organiser - ICMS Pty Ltd