Pharmacogénétique des fluoropyrimidines. La méthylènetétrahydrofolate réductase

Etienne-Grimaldi, M.-C.; Milano, G.
March 2005
Oncologie;mar2005, Vol. 7 Issue 1, p44
Academic Journal
Optimal efficacy of fluoropyrimidines requires elevated concentrations of 5-10 methylenetetrahydrofolate (CH2FH4), controlled by the methylenetetrahydrofolate reductase (MTHFR) which irreversibly converts CH2FH4 into 5-methyltetrahydrofolate (CH3FH4). 677C → T and 1298A → C MTHFR gene polymorphisms are linked to altered enzyme activity. Thus, mutated MTHFR tumours should, in theory, be more sensitive to fluoropyrimidines than wild-type tumours. Experimental and clinical data published so far tend to show an increased antitumour efficacy of 5-FU, with or without folinic acid supplementation, in MTHFR mutated tumours relative to wild-type tumours. Further clinical studies aimed at confirming the influence of MTHFR gene polymorphisms in the outcome of 5-FU-based-treated patients are required.


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