Association of Prostate Cancer with Vitamin D Receptor Haplotypes in African-Americans1

In previous studies, allelic variation in the 3' end of the vitamin D receptor gene was associated with increased risk of prostate cancer in white men. Several polymorphisms, including a BsmI restriction site and a poly(A)microsatellite,can be used interchangeablyto mark the uniden tifled locus in whites. In African-Americans, however, these markers are notinterchangeable, dueto weakerlinkagedisequilibriumin thisgenomic region in this population. Here, we genotyped both the BsmI and poly(A) markersfor 151 African-Americanprostatecancercases (102 localized and 49 advanced) and 174 African-American male controls from a large epidemlological cohort. A direct haplotyping procedure was devised to determine BsmVpoly(A) haplotypes for double heterozygotes so that hap lotypes could be used as allelic markers in standard logistic regression analyses. Using BsmI alone, b alleles were associated with a 2-fold decrease in risk of advanced prostate cancer. The association was, however, con fined to haplotypes carrying a long (L) allele of the poly(A) microsatellite. BL and bL haplotypes were associated with increased and decreased risk, respectively, whereas neither BS nor bS haplotypes were associated with prostate cancer risk. An allelic variant that confers increased risk of advanced prostate cancer appears to be associated with the BsmUpoly(A) BL haplotype in African-Americans.