Promoter Methylation Status of DNA Repair Gene (hMLH1) in Gastric Carcinoma Patients of the Kashmir Valley


Cancer is a multi-factorial disease and variation in genetic susceptibility, due to inherited differences in thecapacity 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 ofmismatch 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 andcontrols, 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 unmethylatedwas achieved with MS-PCR and DNA band patterns. The Chi-square test was applied to assess the risk due topromoter hypermethylation. We found a strikingly high frequency of promoter hypermethylation in GC casesthan in normal samples (72.9% (51/70) in GC cases vs 20% (14/70) in normal samples (p=0.0001).We also observeda statistically significant association between methylated hMLH1 gene promoter and smoking, consumption ofsundried vegetables and hot salted tea with the risk of GC. This study revealed that hMLH1 hypermethylationis strongly associated with GC and suggested roles for epigenetic changes in stomach cancer causation in theKashmir valley.