Abstract
OBJECTIVE: DNMT3B overexpression has been linked with the CpG island methylator phenotype in various cancers. Considering the role of the DNMT3b -149C/T promoter polymorphism on the gene expression, we evaluated the associations of this polymorphism with colorectal cancer (CRC) risk and hypermethylation of six tumor suppressor genes in CRC tumors. METHODS: The DNMT3b was genotyped by PCR-RFLP in 108 sporadic CRC patients and 185 healthy controls and methylation of genes' promoter was determined by methylation specific PCR. RESULTS: In comparison to controls, the TT genotype was strongly associated with a high risk of cancer incidence (OR = 3.3, 95% CI = 1.6-6.9). The frequency of methylated hMLH1 was significantly higher in patients with the DNMT3bCT genotype (p= 0.03), especially in male subjects. The frequency of hMLH1 methylation was significantly higher in young patients (< 60 years) with the CT/TT genotypes. The combined CT/TT genotypes also showed significant associations with the ECAD methylation in the entire group of patients (p= 0.04), in patients with distal tumors, and in old cases. The DNMT3b genotype was not associated with methylation of other genes examined in this study. CONCLUSIONS: Our results suggest that DNMT3b polymorphism is involved in the development of colon cancer and non-random genes promoter methylation among Iranian population.