MTHFR and colorectal carcinoma: The key mechanisms contributing to 5FU resistance in CRC cells include overexpression of thymidylate synthase (TS), an enzyme targeted by 5FU [27,28]; degradation of 5FU by dihydropyrimidine dehydrogenase (DPD) [29,30]; downregulation of methylenetetrahydrofolate reductase (MTHFR) [30] and thymidine phosphorylase (TYMP) [29,31], and enhanced DNA damage repair [32,33].