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Methylenetetrahydrofolate reductase (MTHFR) plays an  important role in folate metabolism and is involved in DNA synthesis, DNA  repair and DNA methylation. The two common functional polymorphisms of MTHFR,  C677T and A1298C have been associated with several diseases, including cancer.  We made a case-control study to analyze a possible association of MTHFR gene  polymorphisms C677T and A1298C with risk for colorectal cancer in an eastern  Chinese Han population of 137 patients with a confirmed histopathological  diagnosis of CRC and 145 age- and gender-matched controls with no history of  cancer. DNA was isolated from peripheral blood samples and the genotypes were  determined by PCR-RFLP. The concentrations of folate in plasma were measured by  chemiluminescence immunoassay. The MTHFR 677TT genotype had a protective effect  against colorectal cancer, with an odds ratio (OR) = 0.467 (95% confidence  interval (CI) = 0.225-0.966). The 1298CC genotype was significantly correlated  with a reduced risk of colorectal cancer (OR = 0.192; 95%CI = 0.040-0.916).  Compared with the MTHFR 677CC and MTHFR 1298 AA genotypes, for individuals who  carried both MTHFR 677CC and 1298CC genotypes, the OR of colorectal cancer was  0.103 (95%CI = 0.012-0.900); among individuals who carried both MTHFR 677TT and  1298AC genotypes, the OR for risk of colorectal cancer was 0.169 (95%CI =  0.044-0.654). MTHFR 677TT+CT genotypes had a significantly lower plasma folate  concentration than those with the MTHFR 677CC genotype. MTHFR 1298AC+CC  genotypes had a lower plasma folate concentration than those with the MTHFR 1298AA  genotype (P &lt; 0.05). In conclusion, subjects with the MTHFR 677TT and MTHFR  1298CC genotypes appeared to have a significantly lower risk for colorectal  cancer. MTHFR haplotypes 677CC/1298CC and 677TT/1298AC were less common in  cases than in controls. These haplotypes, when compared to the most common  haplotype 677CC/1298AA, were associated with a decreased risk for colorectal  cancer. We conclude that plasma folate level is influenced by MTHFR genotypes.

Methylenetetrahydrofolate reductase genotypes and haplotypes associated with susceptibility to colorectal cancer in an eastern Chinese Han population