Aberrant DNA Methylation of P16, MGMT, hMLH1 and hMSH2 with MTHFR SNPs in Gastric Cancer

Gastric cancer is the second leading cause of cancer worldwide, and almost 800 thousands deaths worldwide every year (IARC, 2008). Almost half of the gastric cancer cases and deaths occur in China, and this cancer ranks the third most common cancer (IARC, 2008). The prognosis of gastric cancer was poor, with 20-30% of 5-year survival rate being attributable to the fact that most cases are diagnosed in an advanced stage. However, early detection of gastric cancer is warranted to improve the survival of this cancer. Infection with H.pylori is a well-established cause of gastric cancer, but variants in various genetic factors also influence the susceptibility of gastric cancer (IARC, 1994). Folate is a water-soluble vitamin and naturally found in green leafy vegetables, cereals and fruits (Aune et al., 2011). It is reported that folate metabolism is associated with risk of gastric cancer, and thus variants of folate metabolizing genes may affect the susceptibility of gastric cancer (Miao et al., 2002; Götze et al., 2007). Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme in folate metabolism, and the MTHFR C677Tpolymorphisms are associated with a reduced activity of this protein and risk of gastric cancers (Frosst et al., 1995; Bagley and Selhub, 1998; Neves et al., 2010; Saberi et al., 2012). DNA methylation plays an important role in gene