Influence of MTHFR Genetic Background on p16 and MGMT Methylation in Oral Squamous Cell Cancer.
Influence of MTHFR Genetic Background on p16 and MGMT Methylation in Oral Squamous Cell Cancer.
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DOI：
10.3390/ijms18040724
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发表时间：
2017-03-29
影响因子：
5.6
通讯作者：
Ientile R
中科院分区：
文献类型：
--
作者：
Ferlazzo N;Currò M;Zinellu A;Caccamo D;Isola G;Ventura V;Carru C;Matarese G;Ientile R
亚甲基四氢叶酸还原酶（MTHFR）的遗传多态性可能会影响DNA甲基化。已知参与细胞周期调节、DNA修复、细胞粘附和转移过程的基因的DNA甲基化模式的改变有助于癌症的发展。在这项研究中，MTHFR C677 T和A1298 C基因多态性对口腔鳞状细胞癌（OSCC）患者的p16和O 6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）基因启动子的整体DNA甲基化和位点特异性甲基化的影响进行了研究。为此目的，甲基化研究进行了使用基因组DNA分离唾液样本的58例口腔鳞状细胞癌患者和90名健康对照。CT/AC和TT/AA基因型频率在患者组显著高于对照组。虽然在患者和对照组之间没有观察到总体DNA甲基化水平的差异，但与对照组相比，在患者中检测到p16和MGMT基因启动子的甲基化频率更高。MTHFR基因多态性与p16和MGMT基因启动子甲基化显著相关，CT/AC或TT/AA基因型患者p16和MGMT基因启动子甲基化频率均在60%左右。我们的研究结果表明，癌症相关基因的高甲基化可能受到MTHFR多态性的影响。
Genetic polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) enzyme may influence DNA methylation. Alterations in DNA methylation patterns of genes involved in the regulation of the cell cycle, DNA repair, cell adherence and metastasis process are known to contribute to cancer development. In this study, the influence of the MTHFR C677T and A1298C gene polymorphisms on global DNA methylation and site-specific methylation on p16 and O6-methylguanine-DNA methyltransferase (MGMT) gene promoters was investigated in patients with oral squamous cell cancer (OSCC). To this aim, methylation studies were carried out by using genomic DNA isolated from saliva samples of 58 OSCC patients and 90 healthy controls. The frequency of the CT/AC and TT/AA genotypes was significantly higher in patients than in controls. Whereas no difference in global DNA methylation levels was observed between patients and controls, a higher frequency of methylation at both p16 and MGMT gene promoters was detected in patients compared with controls. A significant association between MTHFR gene polymorphisms and p16 and MGMT gene promoter methylation was found. The frequency of p16 and MGMT methylation was around 60% in patients with either the CT/AC or TT/AA genotype. Our results suggest that hypermethylation of cancer-related genes may be affected by MTHFR polymorphisms.