Abstract 5603: Common genetic variations in VDR, CYP27B1 and CYP24A1 genes and breast cancer risk in African American and European American women in the Women's Circle of Health Study
Authors: Song Yao, Gary Zirpoli, Chi-Chen Hong, Li Tang, Hua Zhao, Lara Sucheston, Jyoti Shankar, Michelle Roberts, Melanie Ruszczyk, Gregory Ciupak, Warren Davis, Helena Hwang, Susan McCann, Elisa Bandera, Christine Ambrosone
Journal: Cancer Research (2011)

Abstract Common single nucleotide polymorphisms (SNPs) in vitamin D receptor (VDR) have been examined with breast cancer risk in populations of European ancestry. Because of the striking differences in vitamin D levels and in SNP linkage disequilibrium (LD) between African Americans (AA) and European Americans (EA), it is hypothesized that associations of VDR SNPs with breast cancer risk may differ by race. A total of 67 multi-population tagSNPs in the VDR, CYP27B1 and CYP24A1 genes were genotyped in 928 breast cancer cases (547 AA and 381 EA) and 843 controls (461 AA and 382 EA) recruited through the Women's Circle of Health Study (WCHS), a case-control study based in New York City and seven counties in New Jersey. Cochran-Armitage test for trend was used for single SNP analysis, and LD block-based haplotype analysis was performed, with multiple comparisons corrected by permutation. In addition, 25-hydroxyvitamin D (25OHD) levels were measured in the banked serum samples from 242 AA and 187 EA healthy women. Four VDR SNPs were associated with breast cancer risk in AA women, and rs2239186 remained significant (p=0.03) after multiple comparison correction. Women with the AG/GG genotype of rs2239186 had a lower risk of breast cancer (OR=0.53, 95% CI=0.35-0.79) than those with the AA genotype, consistent with a three-SNP haplotype carrying the G allele of rs2239186 (OR=0.55, 95% CI=0.38-0.81) in AA women. In EA women, 2 SNPs in the VDR gene and 3 SNPs in the CYP24A1 gene were associated with breast cancer risk. EA women with the TT genotype of the VDR SNP rs11608702 had a significantly increased risk (OR=1.88, 95% CI=1.14-3.09), which were confirmed in an analysis of a two-SNP haplotype carrying the T allele (OR=1.44, 95% CI=1.12-1.85). In addition, a four-SNP haplotype in the CYP24A1 gene was associated with reduced cancer risk in EA women (OR=0.67, 95% CI=0.51-0.88). When stratified by menopausal status, the association of rs7975232 in VDR in EA women was stronger in postmenopausal women (OR=2.24, 95% CI=1.19-4.21); and the association of another VDR SNP rs886441 in AA women was stronger in premenopausal women (OR=2.27, 95% CI=1.32-3.90). Lastly, we found significant differences in 25OHD levels between AA and EA women; the least square mean and standard error were 14.9±0.5 vs 21.4±0.6 ng/mL (p&amp;lt;0.0001), respectively, after adjusting for age, BMI and season of blood collection. Dietary intake of vitamin D helped explain only 3% of the circulating levels. In conclusion, we found different SNPs associated with breast cancer risk between AA and EA women. Our findings support the hypothesis that the role of vitamin D-related genetic variations may be race-specific, possibly due to differences in linkage disequilibrium structure and in endogenous vitamin D levels between the two groups. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5603. doi:10.1158/1538-7445.AM2011-5603