Association of methylenetetrahydrofolate reductase gene polymorphisms & colorectal cancer in India

Background & objectives: Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and involved in DNA synthesis, DNA repair and DNA methylation. The two common functional polymorphisms of MTHFR, 677C -> T and 1298 A -> C have shown to impact several diseases including cancer. This case-control study was undertaken to analyse the association of the MTHFR gene polymorphisms 677 C -> T and 1298 A -> C and risk of colorectal cancer (CRC).Methods: One hundred patients with a confirmed histopathologic diagnosis of CRC and 86 age and gender matched controls with no history of cancer were taken for this study. DNA was isolated from peripheral blood samples and the genotypes were determined by PCR-RFLP. The risk association was estimated by compounding odds ratio (OR) with 95 per cent confidence interval (CI). Results: Genotype frequency of MTHFR 677 CC, CT and TT were 76.7, 22.1 and 1.16 per cent in controls, and 74,25 and 1.0 per cent among patients. The 'T' allele frequency was 12.21 and 13.5 per cent in controls and patients respectively. The genotype frequency of MTHFR 1298 AA, AC, and CC were 25.6, 58.1 and 16.3 per cent for controls and 22, 70 and 8 per cent for patents respectively. The 'C' allele frequency for 1298 A -> C was 43.0 and 45.3 per cent respectively for controls and patients. The OR for 677 CT was 1.18 (95% CI 0.59-2.32, P = 0.642), OR for 1298 AC was 1.68 (95% CI 0.92-3.08, P = 0.092) and OR for 1298 CC was 0.45(95% CI 0.18-1.12, P = 0.081). The OR for the combined heterozygous state (677 CT and 1298 AC) was 1.18(95% CI 0.52-2.64, P =0.697).Interpretation & conclusion: The frequency of the MTHFR 677 TT genotype is rare as compared to 1298 CC genotype in the population studied. There was no association between 677 C -> T and 1298 A -> C polymorphisms and risk of CRC either individually or in combination. The homozygous state for 1298 A -> C polymorphism appears to slightly lower risk of CRC. This needs to be confirmed with a larger sample size

MTHFR 677C T and 1298A C gene polymorphisms and its relation to levels of homocysteine, folate vitamin B12 and vitamin B2 in colorectal cancer

The enzyme 5, 10 methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in folate and homocysteine metabolism. Folate is implicated in carcinogenesis due to its role in DNA methylation, repair and synthesis. In this casecontrol study, we have investigated the association of the MTHFR 677C T and 1298A C gene polymorphisms with plasma levels of folate, vitamin B12, riboflavin and homocysteine in colorectal cancer. Subjects were one hundred cases with histopathologically confirmed colorectal cancer and ninety three age and gender matched healthy controls. Folate and vitamin B12 levels were significantly lower among cases as compared to the control group. Riboflavin status did not differ between the two groups. Homocysteine levels showed an association with the MTHFR genotype. Markedly, elevated homocysteine levels were seen in individuals with the MTHFR 677TT, 1298AC and CC genotypes. An inverse association between vitamin B12 and homocysteine levels was observed in both cases and controls. In conclusion, these results suggest an inverse relation between vitamin B12 and plasma homocysteine levels. The interaction between the genetic polymorphism of MTHFR especially MTHFR 1298A C and increased homocysteine levels and the finding of a higher frequency of the CC genotype in the Indian population is important in terms of its potential impact on hyperhomocysteinemia

Association of methylenetetrahydrofolate reductase gene polymorphisms & colorectal cancer in India

Background & objectives: Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and involved in DNA synthesis, DNA repair and DNA methylation. The two common functional polymorphisms of MTHFR, 677 C→T and 1298 A→C have shown to impact several diseases including cancer. This case-control study was undertaken to analyse the association of the MTHFR gene polymorphisms 677 C→T and 1298 A→C and risk of colorectal cancer (CRC). Methods: One hundred patients with a confirmed histopathologic diagnosis of CRC and 86 age and gender matched controls with no history of cancer were taken for this study. DNA was isolated from peripheral blood samples and the genotypes were determined by PCR-RFLP. The risk association was estimated by compounding odds ratio (OR) with 95 per cent confidence interval (CI). Results: Genotype frequency of MTHFR 677 CC, CT and TT were 76.7, 22.1 and 1.16 per cent in controls, and 74, 25 and 1.0 per cent among patients. The 'T' allele frequency was 12.21 and 13.5 per cent in controls and patients respectively. The genotype frequency of MTHFR 1298 AA, AC, and CC were 25.6, 58.1 and 16.3 per cent for controls and 22, 70 and 8 per cent for patents respectively. The 'C' allele frequency for 1298 A→C was 43.0 and 45.3 per cent respectively for controls and patients. The OR for 677 CT was 1.18 (95% CI 0.59-2.32, P=0.642), OR for 1298 AC was 1.68 (95% CI 0.92-3.08, P=0.092) and OR for1298 CC was 0.45 (95% CI 0.18-1.12, P=0.081). The OR for the combined heterozygous state (677 CT and 1298 AC) was 1.18 (95% CI 0.52-2.64, P=0.697). Interpretation & conclusion: The frequency of the MTHFR 677 TT genotype is rare as compared to 1298 CC genotype in the population studied. There was no association between 677 C→T and 1298 A→C polymorphisms and risk of CRC either individually or in combination. The homozygous state for 1298 A→C polymorphism appears to slightly lower risk of CRC. This needs to be confirmed with a larger sample size