RESUMO
Two TP53 gene polymorphisms at codon 47 (TP53 Pro47Ser) and at codon 72 (TP53 Arg72Pro) have been associated with susceptibility to various cancers. We carried out a case-control study and examined the genotype distribution of TP53 Pro47Ser and Arg72Pro single nucleotide polymorphisms (SNPs), using a PCR-RFLP approach, to determine if these two SNPs are risk factors for colorectal cancer (CRC) development and to look for a possible correlation of these two SNPs with clinicopathological variables of CRC. We investigated the genotype distribution of these SNPs in 86 CRC cases in comparison with 160 healthy subjects in an ethnic Kashmiri population. TP53 Arg72Pro SNP genotype frequencies differed significantly (P = 0.000001) between the groups; the frequency of the Pro/Pro mutant was almost 20% in the general population. We also found significant association of the Pro/Pro mutant with tumor location, nodal status/higher tumor grade and bleeding per rectum/constipation. We conclude that Arg72Pro SNP is associated with susceptibility to developing CRC in this ethnic Kashmiri population.
Assuntos
Substituição de Aminoácidos/genética , Neoplasias Colorretais/genética , Etnicidade/genética , Polimorfismo de Nucleotídeo Único/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Estudos de Casos e Controles , Demografia , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de RestriçãoRESUMO
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.
