TYMS and colorectal carcinoma: While observational studies suggested that higher folate intake was associated with reduced risk of CRC, RCTs did not find a beneficial role in CRC and even a possible increase in CRA.23 Folate also potentially interferes with chemotherapy among CRC patients undergoing active therapy.24 Chemotherapeutical drug fluoropyrimidines, such as 5-fluorouracil (5-FU) or capecitabine, primarily target thymidylate synthase (TS), a key enzyme in nucleotide biosynthesis and folate metabolism.