Aberrant DNA Methylation of P16, MGMT, and hMLH1 Genes in Combination with MTHFR C677T Genetic Polymorphism and Folate Intake in Esophageal Squamous Cell Carcinoma

Abstract

Aim: The present case-control study was conducted to explore the association of MTHFR gene polymorphismand relations of P16, MGMT and HMLH1 to MTHFR and folate intake. <br/><b>Methods</b>: A total of 257 cases ofesophageal squamous cell carcinoma confirmed by histopathological examination were collected. Genotypingof P16, MGMT and HMLH1 was accomplished by methylation-specific polymerase chain reaction (PCR) aftersodium bisulfate modification of DNA and the MTHFR C677T genetic polymorphism was detected by PCRrestrictionfragment-length polymorphism (PCR-RFLP). <br/><b>Results</b>: The proportions of DNA hypermethylation inP16, MGMT and hMLH1 in cancer tissues were significantly higher than in paracancerous normal tissue. Theproportion of hypermethylation in at least one gene was 88.5% in cancer tissue, and was also significantly higherthan that in paracancerous normal tissue. Our finding showed individuals with homozygotes (TT) of MTHFRC677T had significant risk of DNA hypermethylation of MGMT in cancer tissues, with an OR (95% CI) of 3.15(1.12-6.87). Similarly, patients with high intake of folate also showed a slight high risk of DNA methylation ofMGMT, with OR (95% CI) of 2.03 (1.05-4.57). <br/><b>Conclusion</b>: Our study found the P16, MGMT and hMLH1demonstrate a high proportion of hypermethylation in esophageal squamous cell cancer cancer tissues, whichmight be used as biomarkers for cancer detection.