Promoter Methylation of MGMT Gene in Serum of Patients with Esophageal Squamous Cell Carcinoma in North East India


Background: Promoter hypermethylation is a common event in human cancer. O6-methylguanine-DNAmethyltransferase (MGMT) is a gene involved in DNA repair, which is methylated in a variety of cancers. Weaimed to explore the methylation status of MGMT gene among the North Eastern population where esophagealcancer incidence and exposure to carcinogens like nitrosamines is high. Materials and
Methods: A total of 100newly diagnosed esophageal cancer cases along with equal number of age, sex and ethnicity matched controlswere included in this study. Methylation specific PCR was used to determine the MGMT methylation status inserum samples.
Results: Aberrant promoter methylation of the MGMT gene was detected in 70% of esophagealcancer cases. Hypermethylation of MGMT gene was found to be influenced by environmental factors like betelquid and tobacco which contain potent carcinogens like nitrosamines. Tobacco chewing and tobacco smokinghabit synergistically with MGMT methylation elevated the risk for esophageal cancer development [adjustedOR=5.02, 95% CI=1.35-18.74; p=0.010 for tobacco chewing and Adjusted OR=3.00, 95% CI=1.22-7.36; p=0.014for tobacco smoking].
Conclusions: Results suggest that the DNA hypermethylation of MGMT is an importantmechanism for MGMT gene silencing resulting in esophageal cancer development and is influenced by theenvironmental factors. Thus MGMT hypermethylation can be used as a biomarker for esophageal cancer inhigh incidence region of North East India.