Background

Colorectal cancer commonly known as bowel cancer is the third most common cause of cancer-related deaths in the western world and has been reported to show geographical variation in its incidence, even within areas of ethnic homogeneity. Cancer development and progression is dictated by chain of alterations in genes such as tumor suppressor genes, DNA repair genes, oncogenes and others.

Method

The present work was a case control and its aim was to ascertain the role of promoter hypermethylation of CpG islands of hMLH1 gene in colorectal cancer patients among the Kashmiri population. The study was a case-control study. DNA was extracted from all the samples and was modified using bisulphite modification kit. Methylation-specific polymerase chain reaction was used for the analysis of the promoter hypermethylation status of hMLH1 gene.

Results

The epigenetic analysis revealed that unlike other high risk regions, Kashmiri population has a different promoter hypermethylation profile of hMLH1 gene as 67.5 % of the cases showed hMLH1 promoter hypermethylation in comparison to 15 % of the normal cases which also showed promoter hypermethylation of hMLH1 gene. The association of promoter hypermethylation with colorectal cancer was found to be significant (P=0.0006). Occurrence of hMLH1 promoter hypermethylation was found to be unequally distributed in males and females with more frequency in males than in females but the difference was not statistically significant(P =0.7635). Similarly, frequency of hMLH1 promoter hypermethylation was found to be certainly higher in Stage III/IV (85.71%) compared to Stage I/ II (57.69%) but the difference was not statistically significant(P =0.0673).

Conclusion

These results suggest that hMLH1 aberrant promoter hypermethylation in Kashmiri population contributes to the process of carcinogenesis in colorectal cancer and is reportedly one of the commonest epigenetic changes in the development of colorectal cancer.