Saudi Journal of Gastroenterology

ORIGINAL ARTICLE
Year
: 2009  |  Volume : 15  |  Issue : 4  |  Page : 244--252

Molecular gate keepers succumb to gene aberrations in colorectal cancer in Kashmiri population, revealing a high incidence area


A Syed Sameer1, Shakeel Ul Rehman2, Arshad A Pandith2, Nidda Syeed2, Zaffar A Shah2, Nissar A Chowdhri3, Khursheed A Wani3, Mushtaq A Siddiqi2 
1 Department of Immunology and Molecular Medicine, and Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir - 190 011, India
2 Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir - 190 011, India
3 Department of General Surgery, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir - 190 011, India

Correspondence Address:
Mushtaq A Siddiqi
Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir - 190 011
India

Background/Aim: Colorectal cancer (CRC) is one of the leading malignancies worldwide and has been reported to show geographical variation in its incidence, even within areas of ethnic homogeneity. The aim of this study was to identify p53 and K-ras gene mutations in CRC patients in a Kashmiri population, and to assess whether these mutations are linked with clinicopathological parameters. Materials and Methods: Paired tumor and normal tissue samples from a consecutive series of 53 patients undergoing resective surgery for CRC were prospectively studied for p53 and K-ras gene mutations by PCR/single strand conformation polymorphism (SSCP). Results: Less than half (45%, 19/42) of the patients presented mutations in the p53 gene. Twenty eight mutations were found in the p53 gene, which comprised of 23 substitutions (17 transitions + 6 transversions), and five insertions. The 23 substitutions constituted 18 missense mutations, two nonsense mutations, and three silent mutations. Of the 28 mutations (7.14%) observed in this study, 2 were not previously reported for CRC samples and were identified as novel p53 mutations. A few patients (22.64%, 12/53) presented with mutations in K-ras, constituting 13 missense mutations, out of which 11 were G→A transitions, one was a G→C transversion, and one a G→T transversion. More than half (61.5%) of the mutations occurred in codon 12 whereas a few (38.5%) occurred in codon 13. One tumor contained missense mutations in both codons. Comparison of the mutation profiles of our patients with those of other ethnic populations and regions reflected both differences and similarities, indicating co-exposure to a unique set of risk factors. Conclusion: Mutations of the p53 and K-ras genes are some of the most common genetic changes in the development of human CRC. The high frequency of p53 gene mutations implicates p53 as a predominant factor for CRC in the high-risk ethnic Kashmiri population.


How to cite this article:
Sameer A S, Ul Rehman S, Pandith AA, Syeed N, Shah ZA, Chowdhri NA, Wani KA, Siddiqi MA. Molecular gate keepers succumb to gene aberrations in colorectal cancer in Kashmiri population, revealing a high incidence area.Saudi J Gastroenterol 2009;15:244-252


How to cite this URL:
Sameer A S, Ul Rehman S, Pandith AA, Syeed N, Shah ZA, Chowdhri NA, Wani KA, Siddiqi MA. Molecular gate keepers succumb to gene aberrations in colorectal cancer in Kashmiri population, revealing a high incidence area. Saudi J Gastroenterol [serial online] 2009 [cited 2019 Oct 18 ];15:244-252
Available from: http://www.saudijgastro.com/article.asp?issn=1319-3767;year=2009;volume=15;issue=4;spage=244;epage=252;aulast=Sameer;type=0