Mikhak Bahar, Hunter David J, Spiegelman Donna, Platz Elizabeth A, Hollis Bruce W, Giovannucci Edward
Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
Prostate. 2007 Jun 15;67(9):911-23. doi: 10.1002/pros.20570.
The vitamin D receptor (VDR) is required for actions of vitamin D. The binding of 1,25-dihydroxyvitamin D to the VDR on prostatic epithelial cells prompts the regulation of cancer-related genes.
We conducted a nested case-control study in the Health Professionals Follow-up Study to investigate the role of the VDR Cdx2, Fok1, and Bsm1 gene polymorphisms and associated haplotypes and their interaction with plasma vitamin D metabolites in relation to prostate cancer (PC) risk.
No association was found between these SNPs or their associated haplotypes and all PC subtypes except that haplotype 2 (A-f-b) with Cdx2 A, Fok1 f, and Bsm1 b alleles and haplotype 3 (A-F-B) with Cdx2 A, Fok1 F and Bsm1 B alleles compared to the most common haplotype (A-F-b), were associated with reduced risk of aggressive PC (high stage or Gleason sum > or =7; P = 0.02), both with two alleles suspected of being low risk. Carriers of the variant Cdx2 A allele who were deficient in plasma 25-hydroxyvitamin D (< or =15 ng/ml) compared to non-carriers with normal 25-hydroxyvitamin D, had a lower risk of total and poorly differentiated PCs (Gleason sum > or =7) (P for interaction = 0.02 and 0.04, respectively). Plasma 1,25-dihydroxyvitamin D deficiency (< or =26 pg/ml) was associated with a threefold risk of poorly differentiated PC (P for interaction = 0.01) when comparing carriers of the Cdx2 A allele to non-carriers with normal 1,25-dihydroxyvitamin D.
In this population of men, none of the VDR polymorphisms studied was associated with susceptibility to PC.
维生素D受体（VDR）是维生素D发挥作用所必需的。1,25 - 二羟基维生素D与前列腺上皮细胞上的VDR结合可促使癌症相关基因的调控。
我们在健康专业人员随访研究中进行了一项巢式病例对照研究，以调查VDR Cdx2、Fok1和Bsm1基因多态性及其相关单倍型的作用，以及它们与血浆维生素D代谢产物在前列腺癌（PC）风险方面的相互作用。
除了与最常见单倍型（A - F - b）相比，携带Cdx2 A、Fok1 f和Bsm1 b等位基因的单倍型2（A - f - b）以及携带Cdx2 A、Fok1 F和Bsm1 B等位基因的单倍型3（A - F - B）与侵袭性PC（高分期或Gleason总分>或=7；P = 0.02）风险降低相关外，这些单核苷酸多态性（SNP）或其相关单倍型与所有PC亚型之间均未发现关联，这两种单倍型都有两个被怀疑为低风险的等位基因。与25 - 羟基维生素D正常的非携带者相比，血浆25 - 羟基维生素D缺乏（<或=15 ng/ml）的Cdx2 A等位基因变异携带者患总PC和低分化PC（Gleason总分>或=7）的风险较低（交互作用P分别为0.02和0.04）。当比较Cdx2 A等位基因携带者与1,25 - 二羟基维生素D正常的非携带者时，血浆1,25 - 二羟基维生素D缺乏（<或=26 pg/ml）与低分化PC风险增加三倍相关（交互作用P = 0.01）。
在这群男性中，所研究的VDR多态性均与PC易感性无关。
