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Background: Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity. The Kashmir valley, in Northern India, has been described as a high-risk area for colorectal cancer. Aim: The aim was to make a preliminary attempt to study mutations in exons 5-8 (the DNA binding domain) of the tumour suppressor gene TP53 in 42 CRC patients from Kashmir. Materials and methods: The study population consisted of 42 patients diagnosed with colorectal cancer. Mutations in exons 5-8 of the TP53 gene were detected by means of single-strand conformation polymorphism (SSCP). All samples that showed different band migration patterns in the SSCP were confirmed by sequencing. Results: The 28 mutations were found in the TP53 gene in 19 patients, comprised 23 substitutions (17 transitions + six transversions), and five insertions. The 23 substitutions represent 18 missense mutations, leading to amino acid substitutions, two nonsense mutations, leading to stop codons, while the remaining three were silent mutations. The five insertions represented frameshifts. Two of 28 mutations (7.14%) have not been previously reported in colon cancer samples and were identified as novel TP53 mutations. Comparison of the mutation profile with other ethnic populations and regions reflected both differences and similarities indicating co-exposure to a unique set of risk factors. Conclusions: Mutation of the TP53 gene is one of the commonest genetic changes in the development of human colorectal cancer. The high frequency of TP53 gene mutations implicates TP53 as a predominant factor for colorectal cancer in the high-risk ethnic Kashmir population. [ABSTRACT FROM AUTHOR]