Fluorouracil (5-FU) is widely used in the treatment of colorectal cancer. Methylenetetrahydrofolate reductase (MTHFR) could play an important role in the action of 5-FU, an inhibitor of thymidylate synthetase, by converting 5,10-methylenetetrahydrofolate, a substrate of thymidylate synthetase, to 5-methyltetrahydrofolate. A polymorphism in MTHFR (677 C-->T; A222V) reduces enzyme activity and presumably increases the level of 5,10-methylenetetrahydrofolate. This increase would be expected to correlate with an improved response to 5-FU. The aim of the present study was to investigate the association between the MTHFR polymorphism and response to 5-FU and other fluoropyrimidines in patients with metastatic colorectal cancer.
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