Aberrant DNA methylation of P16, MGMT, and hMLH1 genes in combination with MTHFR C677T genetic polymorphism in esophageal squamous cell carcinoma.
Gastric cancer is one of the most common malignant diseases worldwide, which is a disease of multiple etiologic factors involving infectious, dietary, environmental and genetic factors (IRAC, 2008). Helicobacter pylori (H. pylori) infection has been proved to be associated with gastric cancer and duodenal ulcer (Taylor and Blaser, 1991; Munoz, 1994). Folate is a water-soluble vitamin naturally found in green leafy vegetables, cereals and fruits, which is a key B vitamin in one-carbon mechanism and plays an important role in DNA methylation, and DNA synthesis and repair (Jernal et al., 2007). Deficiency of folate has been suggested to increase risk of various cancers through aberrations in DNA methylation and imbalance of DNA precursors (Eichholzer et al., 2001; La et al., 2002; Chen et al., 2002). Methylenetetrahydrofolate reductase (MTHFR) acts centrally in folate metabolism, catalyzing the 5-methylenetetrahydrofolate synthesis reaction, the predominant circulatory form of folate and carbon donor for the remethylation of homocysteine to methionine, which leads to the production of S-adenosylmethionine for DNA methylation (Shen et al., 2001). Two common MTHFR polymorphisms, MTHFR C677T and A1298C,