Mutation pattern of K-ras gene in colorectal cancer patients of Kashmir: A report.

ABSTRACT

Background and Aim: Colorectal cancer (CRC) is one of the leading malignancies worldwide. CRC has been reported to show geographical variation in its incidence, even within areas of ethnic homogeneity. The aim of this study is to identify K-ras gene mutations in CRC patients among the Kashmiri population, and to assess whether they are linked with the clinicopathological parameters. Materials and Methods: Paired tumor and normal tissue samples were collected from a consecutive series of 53 patients undergoing resective surgery for CRC. In addition blood was also collected from all the cases for ruling out germline mutation. Results: Colorectal patients, 22.64% (12 of 53), presented with mutations in K-ras constituting 13 missense mutations out of which 11 were G→A transition, one G→C transversion, and one G→T transversion. 61.5% percent of the mutations occurred in codon 12 and 38.5% in codon 13. One tumor contained missense mutations in both codons. K-ras mutations were significantly associated with advanced Dukes' stage (P < 0.05) and positive lymph node status (P < 0.05). Moreover Codon 12 K-ras mutations were associated with mucinous histotype (P < 0.05). Comparison of the mutation profile with other high-risk areas reflected both mucinous histotype differences and similarities indicating coexposure to a unique set of risk factors. Conclusion: Mutation of the K-ras gene is one of the commonest genetic changes in the development of human CRC, but it occurs in a rather low frequency in Kashmiri population.