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Epigenetic promoter methylation of hmlh1 gene in human gut malignancies: A comparative study

Abstract

Arif A. Bhat, Hilal A. Wani, Mushtaq A. Beigh, Showkat A. Bhat, Showkat Jeelani, Akbar Massood, Sabhiya Majid

Gastrointestinal malignancies (GIT) are a major health hazard globally. The incidence of upper GIT malignancies varies widely based on geographic location, race, and feeding habits etc. GI cancers are most prevalent in Jammu and Kashmir region of India and have multifactorial etiology involving dietary habits, genetic factors, and gene environmental interactions. Cancer development and progression is dictated by series of alterations in genes such as tumour suppressor genes, DNA repair genes, oncogenes and others. Inactivation of the hmlh1 gene expression by aberrant promoter hypermethylation plays an important role in the progression of various cancers. The present study was a hospital based comparative casecontrol study and the aim was to analyse the promoter hypermethylation of CpG islands of hmlh1 gene in G cancer patients of ethnic Kashmiri origin. Methylation-specific polymerase chain reaction (MS-PCR) was used for the analysis of the promoter methylation status of hmlh1 gene. DNA was extracted from all the samples and was modified using bisulphite modification kit. The epigenetic analysis revealed that frequency of Promoter region hypermethylation of hmlh1 gene among gastrointestinal malignancies was found to be higher in colorectal cancer (60%) followed by oesophageal (50%) and then gastric cancer (46%) and statically the association of promoter region hypermethylation with GIT malignancies was found to be significant (p<0.05). The promoter hypermethylation of the hmlh1 gene was found to be more prevalent in respective male cases of all the three GIT malignancies in a statistically significant manner (p<0.05).

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