title: Promoter methylation of MGMT gene in serum of patients with esophageal squamous cell carcinoma in North East India.
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.
  
  
  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.
authors.affiliation: Regional Medical Research Centre, N.E. Region (ICMR), Dibrugarh, Assam, India E-mail : phukanrk@gmail.com.
authors.forename: Mandakini
authors.initials: M
authors.lastname: Das
authors.forename: Santanu Kumar
authors.initials: SK
authors.lastname: Sharma
authors.forename: Gaganpreet Singh
authors.initials: GS
authors.lastname: Sekhon
authors.forename: Bhaskar Jyoti
authors.initials: BJ
authors.lastname: Saikia
authors.forename: Jagadish
authors.initials: J
authors.lastname: Mahanta
authors.forename: Rup Kumar
authors.initials: RK
authors.lastname: Phukan
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000097:blood / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000097:blood / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000097:blood / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes