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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.
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 among 151 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 with 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 with controls with the CC genotype, an increased risk of tumor methylation was associate 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) (OR = 2.5; 95% CI, 1.1-5.6) ) 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 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.