Department of Cancer, Research Center for Gastroenterology and Liver Diseases (RCGLD), Shahid Beheshti University of Medical Sciences, Velenjak, Shahid Chamran Highway, 1985711151, Tehran, Iran.
Mol Biol Rep. 2012 May;39(5):5277-82. doi: 10.1007/s11033-011-1325-x. Epub 2011 Dec 14.
Vitamin D appears to have anti-tumor activities in the large bowel. Our aim was to investigate whether -4817 G>A (rs2238136) polymorphism located at 5'-untranslated region (5'-UTR) of the human vitamin D receptor (VDR) gene was associated with colorectal cancer (CRC) risk. We conducted a case-control study and VDR genotypes, determined by Bpu10I restriction endonuclease digestion of PCR-amplified DNA, were performed on 327 cases with CRC and 327 controls. The distribution of VDR -4817 G>A genotypes and alleles differed significantly between cases with CRC and controls even after adjustment for confounding factors such as age, BMI, sex, and smoking status. Individuals carrying the "AA" genotype had a 2.09-fold increased risk compared with those with "GG" genotype (P = 0.016, OR = 2.09, 95% CI = 1.15-3.78) and a 1.87-fold increased risk compared with those with "GG and GA" genotypes (P = 0.033, OR = 1.87, 95% CI = 1.05-3.33) for CRC. Furthermore, the VDR "A" allele was significantly overrepresented in cases with CRC than controls (P = 0.044; OR = 1.28, 95% CI = 1.01-1.63). Interestingly, the analysis of the SNP revealed that all these associations were stronger for women subjects than for all subjects combined. These data indicated for the first time a direct association between "AA" genotype of VDR gene -4817 G>A polymorphism and CRC, with a stronger association for female subjects. However, our findings remain to be confirmed in other populations.
维生素 D 似乎在大肠中具有抗肿瘤活性。我们的目的是研究位于人维生素 D 受体 (VDR) 基因 5'-非翻译区 (5'-UTR) 的 -4817 G>A(rs2238136) 多态性是否与结直肠癌 (CRC) 风险相关。我们进行了一项病例对照研究，通过聚合酶链反应 (PCR) 扩增 DNA 的 Bpu10I 限制性内切酶消化来确定 VDR 基因型，并对 327 例 CRC 患者和 327 例对照进行了分析。VDR-4817 G>A 基因型和等位基因的分布在 CRC 病例和对照组之间存在显著差异，即使在调整年龄、BMI、性别和吸烟状况等混杂因素后也是如此。与携带“GG”基因型的个体相比，携带“AA”基因型的个体患 CRC 的风险增加了 2.09 倍（P=0.016，OR=2.09，95%CI=1.15-3.78），与携带“GG 和 GA”基因型的个体相比，患 CRC 的风险增加了 1.87 倍（P=0.033，OR=1.87，95%CI=1.05-3.33）。此外，CRC 病例中 VDR“A”等位基因的频率明显高于对照组（P=0.044；OR=1.28，95%CI=1.01-1.63）。有趣的是，对该 SNP 的分析表明，所有这些关联在女性受试者中比在所有受试者中都更强。这些数据首次表明 VDR 基因-4817 G>A 多态性的“AA”基因型与 CRC 之间存在直接关联，女性受试者的关联更强。然而，我们的发现仍需在其他人群中得到证实。
