AIM:To evaluate joint effects of Methylentetra-hydrofolate reductase(MTHFR) C677T genotypes,and serum folate/vitamin B12 concentrations on promoter methylation of tumor-associated genes among Iranian colorectal cancer...AIM:To evaluate joint effects of Methylentetra-hydrofolate reductase(MTHFR) C677T genotypes,and serum folate/vitamin B12 concentrations on promoter methylation of tumor-associated genes among Iranian colorectal cancer patients. METHODS:We examined the associations between MTHFR C677T genotype,and promoter methylation of P16,hMLH1,and hMSH2 tumor-related genes among151 sporadic colorectal cancer patients. The promoter methylation of tumor-related genes was determined by methylation-specific PCR. Eighty six patients from whom fresh tumor samples were obtained and 81 controls were also examined for serum folate and vitamin B12 concentrations by a commercial radioimmunoassay kit. RESULTS:We found 29.1% of cases had tumors with at least one methylated gene promoter. In case-case comparison,we did not find a significant association between methylation in tumors and any single genotype. However,in comparison to controls with the CC genotype,an increased risk of tumor methylation was associated with the CT genotype(OR = 2.5;95% CI,1.1-5.6) . In case-case comparisons,folate/vitamin B12 levels were positively associated with tumor methylation. Adjusted odds ratios for tumor methylation in cases with high(above median) versus low(below median) serum folate/vitamin B12 levels were 4.9(95% CI,1.4-17.7) ,and 3.9(95% CI,1.1-13.9) ,respectively. The frequency of methylated tumors was significantly higher in high methyl donor than low methyl donor group,especially in those with MTHFR CT(P = 0.01) ,and CT/TT(P = 0.002) genotypes,but not in those with the CC genotype(P = 1.0) . CONCLUSION:We conclude that high concentrations of serum folate/vitamin B12 levels are associated with the risk of promoter methylation in tumor-specific genes,and this relationship is modified by MTHFR C677T genotypes.展开更多
基金The office of the Vice Chancellor for Research, Shiraz University of Medical Sciences, No. 83-2212 Grant from the Gastroenterohepatology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran
文摘AIM:To evaluate joint effects of Methylentetra-hydrofolate reductase(MTHFR) C677T genotypes,and serum folate/vitamin B12 concentrations on promoter methylation of tumor-associated genes among Iranian colorectal cancer patients. METHODS:We examined the associations between MTHFR C677T genotype,and promoter methylation of P16,hMLH1,and hMSH2 tumor-related genes among151 sporadic colorectal cancer patients. The promoter methylation of tumor-related genes was determined by methylation-specific PCR. Eighty six patients from whom fresh tumor samples were obtained and 81 controls were also examined for serum folate and vitamin B12 concentrations by a commercial radioimmunoassay kit. RESULTS:We found 29.1% of cases had tumors with at least one methylated gene promoter. In case-case comparison,we did not find a significant association between methylation in tumors and any single genotype. However,in comparison to controls with the CC genotype,an increased risk of tumor methylation was associated with the CT genotype(OR = 2.5;95% CI,1.1-5.6) . In case-case comparisons,folate/vitamin B12 levels were positively associated with tumor methylation. Adjusted odds ratios for tumor methylation in cases with high(above median) versus low(below median) serum folate/vitamin B12 levels were 4.9(95% CI,1.4-17.7) ,and 3.9(95% CI,1.1-13.9) ,respectively. The frequency of methylated tumors was significantly higher in high methyl donor than low methyl donor group,especially in those with MTHFR CT(P = 0.01) ,and CT/TT(P = 0.002) genotypes,but not in those with the CC genotype(P = 1.0) . CONCLUSION:We conclude that high concentrations of serum folate/vitamin B12 levels are associated with the risk of promoter methylation in tumor-specific genes,and this relationship is modified by MTHFR C677T genotypes.
