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

Departments of Preventive Medicine [S. A. I., R. K. R., B. E. H., W. W., R. W. H.] and Urology [G. A. C., L. C.], University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California 90033; and Cancer Research Center, University of Hawaii, Honolulu, Hawaii 96813 [L. N. K.]

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 interchangeably to mark the unidentified locus in whites. In African-Americans, however, these markers are not interchangeable, due to weaker linkage disequilibrium in this genomic region in this population. Here, we genotyped both the BsmI and poly(A) markers for 151 African-American prostate cancer cases (102 localized and 49 advanced) and 174 African-American male controls from a large epidemiological cohort. A direct haplotyping procedure was devised to determine BsmI/poly(A) haplotypes for double heterozygotes so that haplotypes 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, confined 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 BsmI/poly(A) BL haplotype in African-Americans.

¹ This work was supported by NIH Grants R01 CA68572 and R01 CA54281.

² To whom requests for reprints should be addressed, at Department of Preventive Medicine, University of Southern California/Norris Cancer Center, 1441 Eastlake Avenue, MS 44, Room 5411, Los Angeles, California 90033. Phone: (213) 764-0498; Fax: (213) 764-0473; E-mail: ingles@hsc.usc.edu.

Received 1/ 9/98. Accepted 2/27/98.

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