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http://dx.doi.org/10.7314/APJCP.2014.15.22.9955

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

Das, Mandakini (Regional Medical Research Centre, N.E. Region (ICMR))
Sharma, Santanu Kumar (Regional Medical Research Centre, N.E. Region (ICMR))
Sekhon, Gaganpreet Singh (Regional Medical Research Centre, N.E. Region (ICMR))
Saikia, Bhaskar Jyoti (Regional Medical Research Centre, N.E. Region (ICMR))
Mahanta, Jagadish (Regional Medical Research Centre, N.E. Region (ICMR))
Phukan, Rup Kumar (Regional Medical Research Centre, N.E. Region (ICMR))
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.22, 2014 , pp. 9955-9960 More about this Journal
Abstract
Background: Promoter hypermethylation is a common event in human cancer. O6-methylguanine-DNA methyltransferase (MGMT) is a gene involved in DNA repair, which is methylated in a variety of cancers. We aimed to explore the methylation status of MGMT gene among the North Eastern population where esophageal cancer incidence and exposure to carcinogens like nitrosamines is high. Materials and Methods: A total of 100 newly diagnosed esophageal cancer cases along with equal number of age, sex and ethnicity matched controls were included in this study. Methylation specific PCR was used to determine the MGMT methylation status in serum samples. Results: Aberrant promoter methylation of the MGMT gene was detected in 70% of esophageal cancer cases. Hypermethylation of MGMT gene was found to be influenced by environmental factors like betel quid 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 [adjusted OR=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=0.014 for tobacco smoking]. Conclusions: Results suggest that the DNA hypermethylation of MGMT is an important mechanism for MGMT gene silencing resulting in esophageal cancer development and is influenced by the environmental factors. Thus MGMT hypermethylation can be used as a biomarker for esophageal cancer in high incidence region of North East India.
Keywords
Esophageal cancer; North East India; MGMT; methylation; biomarker;
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