Alterations in K-ras, APC and p53-multiple genetic pathway in colorectal cancer among Indians
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The incidence of colorectal cancer (CRC) is increasing rapidly in Asian countries during the past few decades, but no comprehensive analysis has been done to find out the exact cause of this disease. In this study, we investigated the frequencies of mutations and expression pattern of K-ras, APC (adenomatosis polyposis coli) and p53 in tumor, adjoining and distant normal mucosa and to correlate these alterations with patients clinicopathological parameters as well as with the survival. Polymerase chain reaction (PCR)-restriction digestion was used to detect mutations in K-ras and PCR-SSCP (Single Strand Conformation Polymorphism) followed by DNA sequencing was used to detect mutations in APC and p53 genes. Immunohistochemistry was used to detect the expression pattern of K-ras, APC and p53 proteins. The frequencies of mutations of K-ras, APC and p53 in 30 tumor tissues samples were 26.7 %, 46.7 % and 20 %, respectively. Only 3.3 % of tumors contained mutations in all the three genes. The most common combination of mutation was APC and p53 whereas mutation in both p53 and K-ras were extremely rare. There was no association between the mutations and expression pattern of K-ras, APC and p53 (p > 0.05). In Indians, the frequency of alterations of K-ras and APC is similar as in Westerns, whereas the frequency of p53 mutation is slightly lower. The lack of multiple mutations in tumor specimens suggests that these genetic alterations might have independent influences on CRC development and there could be multiple alternative genetic pathways to CRC in our present study cohort.
KeywordsColorectal cancer APC K-ras p53 Mutation
We acknowledge the staff of OT, and Exp. Med and Biotech for their support and help in collecting the samples. Financial assistance from Indian Council of Medical research (ICMR), New Delhi is highly acknowledged.
Conflicts of interest
- 2.Parkin DM, Muir CS, Whelan SL, Gao JT, Ferlay J, Powell J. Cancer Incidence in five continents, comparability and quality of data. Intl Agency Res Cancer Lyon France. 1992;120:45–173.Google Scholar
- 15.Sriram PVJ, Kochhar R, Bhasin DK, Vaiphei K, Goenka MK, Singh K. Colonoscopic surveillance for synchronous lesions in colorectal carcinoma in north India. Eur J Cancer Supp. 1998;2(34):S16.Google Scholar
- 16.Sambrook J, Russell DW. Molecular cloning: a laboratory manual. 3rd ed. Cold Spring Harbor: Cold Spring Harbor Laboratory Press; 2001. p. 6.4–6.12.Google Scholar