title: Diminished expression ofMGMT&RASSF1Agenes in gastric cancer in ethnic population of Kashmir.
abstract: BACKGROUND
  Cancer initiation and progression are accompanied by profound changes in DNA. DNA methylation that was the first epigenetic alterations identified in cancer. DNA hypermethylation at promoter sites is closely associated with down regulation of protein and as major participant in the development and progression of series of human tumors. Therefore we hypothesized that promoter hypermethylation ofRASSF1A&MGMTgene could influence susceptibility to gastric cancer (GC) as well, and we conducted this study to test the hypothesis in Kashmiri population.
  
  
  METHODS
  A hospital based case-control study; including 200 GC cases and 200 matched controls from patients who went surgical resection. Promoter hypermethylation was determined by Methylation Specific Polymerase chain reaction. The expression of MGMT & RASSF1A protein was examined by Western blotting technique.
  
  
  RESULTS
  Frequency of promoter region hypermethylation ofMGMTgene were 46.5% in cases and 5.5% in controls (P<0.05) while as in case of RASSF1A frequency was 44% in cases and 4.5% in controls (P<0.05). Further, frequency of hypermethylation of both genes was found predominant in males, aged and advanced pathological stage subjects. Loss of MGMT expression was found in 46.5% cases (P<0.05) while as loss of RASSF1A expression was found in 40.5% cases (P<0.05). In both genes a positive correlation was observed between promoter CpG island hypermethylation and down regulation of respective proteins.
  
  
  CONCLUSIONS
  These findings indicate that promoter hypermethylation at CpG island may be responsible for reduction of expression at protein level which may be an initial event in carcinogenesis and the progression of GC.
authors.affiliation: Department of Biochemistry, Government Medical College Srinagar (Research Centre University of Kashmir), Srinagar, India.
authors.forename: Arif Akbar
authors.initials: AA
authors.lastname: Bhat
authors.affiliation: Multidisciplinary Research Unit, Government Medical College Srinagar, Srinagar, India.
authors.forename: Hilal Ahmad
authors.initials: HA
authors.lastname: Wani
authors.affiliation: Department of Biotechnology, University of Kashmir, Hazratbal Srinagar, India.
authors.forename: Ajaz Ahmad
authors.initials: AA
authors.lastname: Waza
authors.affiliation: Department of Human Genetics, Punjabi University Patiala, Punjab, India.
authors.forename: Rawoof Ahmad
authors.initials: RA
authors.lastname: Malik
authors.affiliation: Department of Biochemistry, University of Kashmir, Hazratbal Srinagar, Srinagar, India.
authors.forename: Akbar
authors.initials: A
authors.lastname: Masood
authors.forename: Showkat
authors.initials: S
authors.lastname: Jeelani
authors.forename: Showkat
authors.initials: S
authors.lastname: Kadla
authors.affiliation: Department of Biochemistry, Government Medical College Srinagar (Research Centre University of Kashmir), Srinagar, India.
authors.forename: Sabhiya
authors.initials: S
authors.lastname: Majid
keywords: CpG island; Methylation specific PCR; epigenetics, hypermethylation; gastric cancer (GC)