title: Promoter methylation status of DNA repair gene (hMLH1) in gastric carcinoma patients of the Kashmir valley.
abstract: Cancer is a multi-factorial disease and variation in genetic susceptibility, due to inherited differences in the capacity to repair mismatches in the genome, is an important factor in the development of gastric cancer (GC), for example. Epigenetic changes, including aberrant methylation of 5/CpG islands in the promoter regions of mismatch repair (MMR) genes like hMLH1, have been implicated in the development of various types of GC. In the present study we evaluated the role of hMLH1 promoter hypermethylation in Kashmiri GC patients and controls, and assessed correlations with various dietary and lifestyle factors. The study included 70 GC patients (56 males and 14 females; age (mean ± S.D) 50 ± 11.4 years). Distinction between methylated and unmethylated was achieved with MS-PCR and DNA band patterns. The Chi-square test was applied to assess the risk due to promoter hypermethylation. We found a strikingly high frequency of promoter hypermethylation in GC cases than in normal samples (72.9% (51/70) in GC cases vs 20% (14/70) in normal samples (p=0.0001). We also observed a statistically significant association between methylated hMLH1 gene promoter and smoking, consumption of sundried vegetables and hot salted tea with the risk of GC. This study revealed that hMLH1 hypermethylation is strongly associated with GC and suggested roles for epigenetic changes in stomach cancer causation in the Kashmir valley.
authors.affiliation: Department of General Surgery, Sher I Kashmir Institute of Medical Sciences, Srinagar, India.
authors.forename: Majid
authors.initials: M
authors.lastname: Wani
authors.forename: Dil
authors.initials: D
authors.lastname: Afroze
authors.forename: Muzamil
authors.initials: M
authors.lastname: Makhdoomi
authors.forename: Iqra
authors.initials: I
authors.lastname: Hamid
authors.forename: Bilal
authors.initials: B
authors.lastname: Wani
authors.forename: Gulzar
authors.initials: G
authors.lastname: Bhat
authors.forename: Rauf
authors.initials: R
authors.lastname: Wani
authors.forename: Khursheed
authors.initials: K
authors.lastname: Wani
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000473:pathology; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D004260:DNA Repair / Q000235:genetics; D005260:Female; D006801:Humans; D007194:India; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1