Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.
Cancer Epidemiol Biomarkers Prev. 2012 Oct;21(10):1856-67. doi: 10.1158/1055-9965.EPI-12-0551. Epub 2012 Aug 14.
Observational and experimental studies suggest that vitamin D may influence breast cancer etiology. Most known effects of vitamin D are mediated via the vitamin D receptor (VDR). Few polymorphisms in the VDR gene have been well studied in relation to breast cancer risk and results have been inconsistent.
We investigated VDR polymorphisms and haplotypes in relation to breast cancer risk by genotyping 26 single nucleotide polymorphisms (SNP) that (i) had known/suspected impact on VDR function, (ii) were tagging SNPs for the three VDR haplotype blocks among whites, or (iii) were previously associated with breast cancer risk. We estimated odds ratios (OR) and 95% confidence intervals (CI) in relation to breast cancer risk among 270 incident cases and 554 matched controls within the Agricultural Health Study cohort.
In individual SNP analyses, homozygous carriers of the minor allele for rs2544038 had significantly increased breast cancer risk (OR = 1.5; 95% CI: 1.0-2.5) and homozygous carriers of the minor allele for rs11168287 had significantly decreased risk (OR = 0.6; 95% CI: 0.4-1.0). Carriers of the minor allele for rs2239181 exhibited marginally significant association with risk (OR = 1.4; 95% CI: 0.9-2.0). Haplotype analyses revealed three haplotype groups (blocks "A," "B," and "C"). Haplotype GTCATTTCCTA in block B was significantly associated with reduced risk (OR = 0.5; 95% CI: 0.3-0.9).
These results suggest that variation in VDR may be associated with breast cancer risk.
Our findings may help guide future research needed to define the role of vitamin D in breast cancer prevention.
观察性和实验研究表明，维生素 D 可能影响乳腺癌的病因。维生素 D 的大多数已知作用是通过维生素 D 受体 (VDR) 介导的。VDR 基因中的少数多态性与乳腺癌风险的关系已经得到了很好的研究，但结果并不一致。
我们通过对 26 个单核苷酸多态性 (SNP) 进行基因分型，研究了 VDR 多态性和单倍型与乳腺癌风险的关系，这些 SNP （i）对 VDR 功能有已知/疑似影响，（ii）是白人三个 VDR 单倍型块的标记 SNP，或（iii）先前与乳腺癌风险相关。我们在农业健康研究队列中，对 270 例新发病例和 554 例匹配对照进行了与乳腺癌风险相关的比值比 (OR) 和 95%置信区间 (CI) 的估计。
在个体 SNP 分析中，rs2544038 中的次要等位基因纯合子携带者的乳腺癌风险显著增加（OR = 1.5；95%CI：1.0-2.5），rs11168287 中的次要等位基因纯合子携带者的乳腺癌风险显著降低（OR = 0.6；95%CI：0.4-1.0）。rs2239181 的次要等位基因携带者与风险呈边缘显著相关（OR = 1.4；95%CI：0.9-2.0）。单倍型分析显示出三个单倍型组（块“A”、“B”和“C”）。块 B 中的 GTCATTTCCTA 单倍型与风险降低显著相关（OR = 0.5；95%CI：0.3-0.9）。
这些结果表明，VDR 的变异可能与乳腺癌风险相关。
我们的发现可能有助于指导未来需要定义维生素 D 在乳腺癌预防中的作用的研究。
