The Association Between The MTHFR C677T,SHMT₁ C1420T SNPs, The Aberrant Methylation Of The MAGE A₁,CAGE Gene And The Carcinogenesis And Development Of ESCC

Objective:More and more studies show that the epigenetic mechanism plays an important role in carcinogenesis. Methylation is one of the major way of the epigenetic mechanism. Aberrant methylation, the methylation of tumor suppressor genes and the demethylation of oncogenes, is believed to be the main mechanism for activating the oncogene and inactivating the tumor suppressor gene. Researches on aberrant methylation will provide useful information for selecting targets of cancer prevention and treatment, because of the reversible and heritable characters of methylation. Folate, as a carrier of methyl and formyl groups, is considered to play a protective role against cancer development by intracellular trans-methylation reactions. Although folate deficiency is associated with carcinogenesis of various cancer, it could not be utilized directly by the body untill being transmitted to the live substance catalyzed by the folate metabolism enzyme. Interruption during the folate metabolism may cause the similar subsequence to that of folate deficiency. Methylenetetrahydrofolate reductase (MTHFR) and serine hydroxymethyltransferase1 (SHMT1) are the key enzymes in regulating the folate metabolism. The polymorlphisms in the MTHFR and SHMT1 genes may influence the activities of the enzymes, and alter the production of methl and dTMP. These polymorphisms have been associated with the susceptibility of many cancers. Malenoma antigen(MAGE) and cancer-associated antigen (CAGE) are two cancer/testis associated antigens which have been reported to be demethylated in some tumor tissues. To study the role of the MTHFR C677T, SHMT1 C1420T SNPs and aberrant methylation of the MAGE A1 and CAGE genes in the development of esophageal squamous cell carcinoma, we tested the distribution of the MTHFR C677T and SHMT1 C1420T SNPs among...