Promoter hypermethylation of KLOTHO; an anti-senescence related gene in colorectal cancer patients of Kashmir valley

Hypermethylation of CpG islands located in the promoter regions of genes is a major event in the development of the majority of cancer types, due to the subsequent aberrant silencing of important tumor suppressor genes. KLOTHO; a novel gene associated primarily with suppressing senescence has been shown to contribute to tumorigenesis as a result of its impaired function. Recently the relevance of KLOTHO promoter hypermethylation in colorectal carcinoma in humans has been reported. We analyzed the promoter hypermethylation of KLOTHO gene in 50 histopathologically confirmed tumor and adjacent normal tissues of colorectal cancer patients. Methylation was assessed by bisulfite conversion of DNA followed by methylation specific-polymerase chain reaction. Methylation status was compared with gender, smoking status and histopathological parameters of patients. Promoter hypermethylation in KLOTHO gene was detected in 86% (43/50) of tumor tissues and 14% (7/50) of adjacent normal tissues. The methylation pattern differed significantly between tumor and adjacent normal tissues (P<0.0001). However, no association was found between promoter hypermethylation status and gender (P=0.68), smoking status (P=0.64) or other histopathological parameters (P>0.05) of colorectal cancer patients. We conclude that this novel tumor suppressor gene is epigenetically inactivated in colorectal cancer in our population paving way towards the potential of KLOTHO promoter hypermethylation as a predictor of the prognosis in colorectal cancer patients.