The effects of thymidylate synthase 3'UTR genotype on methylation of tumor-specific genes promoter in 22 colorectal cancer patients from southern Iran.

To investigate the effects of 3'UTR genotype on promotor methylation of tumor-related genes in 22 patients with sporadic colorectal cancer (CRC) from southern Iran. We evaluated the correlations of 3'UTR genotype with promoter methylation of and genes in CRC patients. The polymorphism of 3'UTR was evaluated through mutagenically specific PCR. The genes promoter methylation was determined using methylation-specific PCR. For 10 patients, the gene expression profile of epigenetic regulating enzymes, and was also examined in both tumor and normal adjacent tissues by quantitative real time PCR. There was a significant association between the methylation and age of patients (= 0.039) and also between methylation and tumor site (= 0.036). There was insignificant association between gene-specific methylation and 3'UTR genotype. However, all polymorphic genotypes of were associated with higher methylation of and and lower methylation of . The -6bp/+6bp (heterozygous mutant) and [-6bp/+6bp, +6bp/+6bp] (homozygous mutant) genotypes resulted in higher methylation of , and -6bp/+6bp and [-6bp/+6bp, +6bp/+6bp] genotypes were correlated with lower methylation of . The overexpression of epigenetic enzymes, and was also demonstrated. There was no association between DNMTs transcript levels and gene-specific hypermethylation. The polymorphic TS genotypes, especially -6bp/+6bp, could affect methylation frequencies of studied genes. Moreover, promoter methylation status was not dependent on gene expression. Large sample size studies may contribute to validate these findings.