RESUMO
INTRODUCTION: Adequate intake of folates has been associated to low prevalence of colon cancer. Methylenetetrahydrofolate reductase enzyme (MTHFR) plays an important role in folate metabolism. The role of the 677 mutation at the MTHFR gene in the risk for colorectal cancer remains controversial. A recent report established that this mutation has a high prevalence in the healthy Mexican population. AIMS: To analyze the prevalence of 677T MTHFR mutation in patients with colorectal cancer and controls without chronic gastrointestinal disorders. METHODS: Seventy-four colorectal cancer, 32 adenomas and 110 normal samples were analyzed. Patients and controls were matched for sex and age. For each sample, DNA isolation, PCR, and mutation detection by restriction enzyme digestion were performed to determine the allele at the 677 position in the MTHFR gene. RESULTS: Genotype 677C/677C was found in 18.7, 20.3, and 30.9% in adenomas, cancer lesions and controls, respectively. Frequencies of the 677C/677T genotype were 59.4, 56.7, and 47.3%, in adenomas, cancer lesions, and controls, respectively. Genotype 677T/677T was found in 21.9, 23.0, and 21.8% in adenomas, cancer lesions, and controls, respectively. The odds ratio between genotypes carrying the mutation (T/T and C/T) and normal genotype (CC) was 1.81 (IC 95% 0.97-3.3), chi 2 = 3.5, p = 0.06. CONCLUSION: Our results showed that persons who carry the 677T mutation at MTHFR locus have a tendency for an increased risk for colorectal cancer. This study supports the basic concept that low levels of folic acid contribute with the colorectal cancer pathogenesis. Our lack of statistic significance may be due to reduced sample size.
Assuntos
Adenoma/genética , Neoplasias Colorretais/genética , Mutação , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Feminino , Genótipo , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2) , México , Pessoa de Meia-IdadeRESUMO
Activation of the ras family gene has been implicated in colorectal tumorigenesis, K-ras being the most frequently altered gene. The frequency of K-ras codon 12, 13 and 61 point mutations in patients with colorectal neoplasias was examined. We employed a polymerase chain reaction-restriction fragment length polymorphism assay and single-strand conformational polymorphism to detect mutations. We found that point mutations at codons 12 and 13 were present in 53% and 39% of the tumors, respectively, but none at codon 61. These results agree with previous reports. Point mutations were more frequent in adenomas than in carcinomas, with villous adenomas presenting a higher incidence of mutations than other adenomas. The association between clinical and histopathological parameters was investigated. Our study is the beginning of a new research line in molecular epidemiology of colorectal cancer and is the first to be carried out in one part of the Mexican population.