Mandakini Das is currently working as a Research Scientist I under Department of Health Research, Ministry of health and family welfare, Regional Medical Research Centre, Dibrugarh, India. She has completed her M.Sc Biochemistry from Bangalore University in 2011. She has recently completed her Ph.D. from Dibrugarh University, Assam, India. Her Ph.D. thesis was focused on epigenetic modifications associated with esophageal cancer in Assam, a high incidence region of North East India. She has more than 8 publications in international journals of repute. She was awarded the ICMR young scientists travel grant to attend the Global Biotechnology Congress, 2014 held at Hyne’s Convention Centre, Boston, USA. She is also the recipient of the best poster award for her work on “Esophageal Cancer scenario in North East India: Epigenetic Perspective” at the 4th International Conference on Stem Cells and Cancer (ICSCC-2013); Proliferation, Differentiation and Apoptosis organized by International Centre for Stem Cells, Cancer and Biotechnology (ICSCCB), Pune, India.
Promoter hypermethylation is a common event in human cancer. O6-Methylguanine-DNA Methyltransferase (MGMT) and Human Mut L homolog (hMLH1) are two important DNA repair genes, which are frequently methylated in a variety of cancers. We aimed to explore the methylation status of MGMT and hMLH1 genes among the North Eastern population where esophageal cancer incidence and exposure to carcinogens like nitrosamines is alarmingly high. A case-control study was designed and accordingly blood samples from 150 cases and an equal number of controls were included in the study. 30 esophageal tumor tissues and their corresponding adjacent normal tissues were used as controls. MGMT promoter methylation was detected in 107 of 150 (71.3%) blood samples of esophageal cancer cases and 21 of 30 (70%) corresponding esophageal cancer tumor tissue. However, in a case of controls, only 6.66% MGMT promoter methylation was observed in the peripheral blood samples of healthy controls and in an adjacent normal tissue of patients. hMLH1 promoter methylation was detected in 57 of 150 (38%) blood samples of esophageal cancer cases and 11 of 30 (36.7%) corresponding esophageal cancer tumor tissue. However, in a case of controls, only 5% of hMLH1 promoter methylation was observed in peripheral blood of healthy controls and in an adjacent normal tissue of patients. Hypermethylation of MGMT and hMLH1 genes were found to be influenced by environmental factors like betel nut and tobacco which contain potent carcinogens like nitrosamines. Tobacco chewing and tobacco smoking habit synergistically with MGMT methylation elevated the risk for esophageal cancer development [OR=5.26, 95% CI=2.46-11.24, p<0.001 for Tobacco chewing and OR=2.61, 95% CI=1.26-5.42,p=0.009 for tobacco smoking]. Tobacco chewing with hMLh1 methylation too conferred a significant risk towards esophageal cancer development (OR=4.04, 95% CI=1.83-8.95, p<0.001).The result in our present study indicated that aberrant methylation of MGMT and hMLH1 genes are frequent events in the occurrence of esophageal cancer in North East India. Further, environmental risk factors act as effect modifiers and these risk factors in conjunction with MGMT and hMLH1 methylation elevated the risk of esophageal cancer in this region. MGMT and hMLh1 methylation can, therefore, be used as a biomarker for esophageal cancer detection in high incidence region of North East India.