ABSTRACT
BACKGROUND AND AIM: The present study was designed to consider whether amino acid substitution polymorphisms in O6-methylguanine-DNA methyltransferase (MGMT) and DNA methyl transferase 1 (DNMT1) genes may be associated with the genetic susceptibility to sporadic colorectal cancer. PATIENTS AND METHODS: We assessed eight non-synonymous polymorphisms of these two genes by PCR/pyrosequencing. Our population consisted of 208 individuals with sporadic colorectal cancer and 213 controls. Allele frequencies and genotypes were compared between the two groups. RESULTS: The calculated odds ratios indicated no association between DNMT1 and colorectal cancer. However, there was a significant association between two polymorphisms in MGMT with sporadic colorectal cancer: Arg128Gln (OR, 5.53; 95% CI) and Gly160Arg (OR, 3.04; 95% CI). CONCLUSIONS: These findings could be indicative of factors contributing to high occurrence of Iranian colorectal cancer patients.
Subject(s)
Amino Acid Substitution , Colorectal Neoplasms/genetics , DNA Modification Methylases/genetics , DNA Repair Enzymes/genetics , Polymorphism, Single Nucleotide , Repressor Proteins/genetics , Tumor Suppressor Proteins/genetics , Adult , Case-Control Studies , Colorectal Neoplasms/epidemiology , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Iran/epidemiology , Male , Middle Aged , Polymerase Chain ReactionABSTRACT
BACKGROUND: Gastric cancer is one of the most common malignant tumors in Iran. Hypomethylation and/or hypermethylation of DNA has been described in gastric cancer and is presumed to be an early event in carcinogeneisis. OBJECTIVE: We therefore hypothesized that single nucleotide polymorphisms of the DNMT1 gene may be associated with the genetic susceptibility to gastric cancer. METHODS: Totals of 200 patients and 200 controls, both of Iranian origin, were studied. Three polymorphisms were genotyped by PCR-RFLP and allele frequencies and genotypes were compared between the cases and controls. Odds ratios were calculated and the interactions between the polymorphisms, age and sex were examined. RESULTS: There were no significant associations between the DNMT1 polymorphisms and gastric cancer. CONCLUSION: We could not show any association between DNMT1 polymorphisms and gastric cancer. Larger sets of polymorphisms and sample sizes are required for future testing of possible associations.
