MTHFR and cancer: For example, Safarinejad et al. [27] reported that reduced levels of MTHFR mRNA had an increased association with the risk in men bladder cancer, which may be explained by the hypothesis that reduced MTHFR mRNA level may influence the metabolism of folic acid, then decrease supply of 5-MTHF in serum, along with the increase other forms of folic acid, which leads to affect the synthesis of the pyrimidine and purine, resulting in damaged in DNA synthesis and repair, finally contributes to cancer development.