Asian Pac J Cancer Prev, 14 (11), [6249][6250][6251][6252][6253][6254][6255][6256] IntroductionThe one-carbon metabolism has drawn considerable attention in relation to colorectal carcinogenesis (Ulrich, 2005;Hubner and Houlston, 2009;Williams, 2012). A folate metabolite, 5-methyl tetrahydrofolate (THF), provides the methyl group in the reaction by methionine synthase (MTR) to convert homocysteine to methionine, the precursor of S-adenosylmethionine (SAM). The SAM is the universal methyl-group donor for methylation of a wide variety of biological substrates. Thus folate/methyl depletion results in aberrant DNA methylation, i.e., global genomic hypomethylation and specific methylation of CpG clusters in the promoters of tumor suppressor and DNA repair genes. Methylenetetrahydrofolate reductase (MTHFR) irreversibly converts 5, 10-methylene THF (Ulrich, 2005). Vitamin B 2 is the precursor for a cofactor of MTHFR. Vitamin B 6 is not only a cofactor for cystathionin beta-synthase (CBS) to convert homocystein to cystathionine but also is required in the conversion of serine to glycine, recycling THF (derivative of 5-methyl THF after methyl-transfer to homocysteine) to 5, 10-methylene THF. Vitamin B 12 is a coenzyme of MTR. MTR reductase (MTRR) catalyzes the reduction of