Gao Shang, Ding Li-Hong, Wang Jian-Wei, Li Cun-Bao, Wang Zhao-Yang
Department of Anthropotomy, School of Basic Medicine, Inner Mongolia Medical University, Hohhot, China.
Asian Pac J Cancer Prev. 2013;14(1):299-302. doi: 10.7314/apjcp.2013.14.1.299.
Methylenetetrahydrofolate reductase (MTHFR) has been reported to be associated with DNA methylation, an epigenetic feature frequently found in gastric cancer. We conducted a case-control study to explore the association of MTHFR C677T polymorphisms with gastric cancer risk and its relation with the DNA methylation of COX-2, MGMT, and hMLH1 genes. Genotyping of P16, MGMT and HMLH1 was determined by methylation-specific PCR after sodium bisulfate modification of DNA, and genotyping of MTHFR C677T was conducted by TaqMan assays using the ABI Prism 7911HT Sequence Detection System. Folate intake was calculated with the aid of a questionnaire. Compared with the MTHFR 677CC genotype, the TT genotype was significantly associated with 2.08 fold risk of gastric cancer when adjusting for potential risk factors. Individuals who had an intake of folate above 310 μg/day showed protective effects against gastric cancer risk. The effect of MTHFR C677T polymorphisms on the risk of gastric cancer was modified by folate intake and methylation status of MGMT (P for interaction <0.05).
据报道，亚甲基四氢叶酸还原酶（MTHFR）与DNA甲基化有关，DNA甲基化是胃癌中常见的一种表观遗传特征。我们进行了一项病例对照研究，以探讨MTHFR C677T基因多态性与胃癌风险的关联及其与COX-2、MGMT和hMLH1基因DNA甲基化的关系。DNA经亚硫酸氢盐修饰后，采用甲基化特异性PCR法对P16、MGMT和HMLH1进行基因分型，使用ABI Prism 7911HT序列检测系统通过TaqMan分析对MTHFR C677T进行基因分型。借助问卷计算叶酸摄入量。在调整潜在风险因素后，与MTHFR 677CC基因型相比，TT基因型与胃癌风险显著相关，风险为2.08倍。叶酸摄入量超过310μg/天的个体对胃癌风险具有保护作用。MTHFR C677T基因多态性对胃癌风险的影响因叶酸摄入量和MGMT的甲基化状态而改变（交互作用P<0.05）。
