ABSTRACT

Pharmacogenetics investigates the molecular basis of inter-individual differences in drug metabolism and response. Sequence variations in genes encoding for metabolic enzymes may influence drug’s pharmacokinetics and/or pharmacodynamics, resulting in reduced efficacy and/or adverse drug reactions. The dihydropyrimidine dehydrogenase (DPD) deficiency is a clear example of how gene variants may affect fluoropyrimidines metabolism, and its evaluation has been recently recommended from regulatory agencies for its implementations in clinical routine. This review provides a summary of pharmacogenetic research on DPD and fluoropyrimidines metabolism, and its involvement n adverse drug reactions.

IMPACT STATEMENT

Dihydropyrimidine dehydrogenase (DPD) is the major responsible for fluoropyrimidines metabolism and its deficiency may led to life-threatening toxicities. Although the frequency of DPD deleterious variants is low, their screening is clinically relevant to avoid severe toxicities or death in patients treated with fluoropyrimidine-based chemotherapy.  While for the most studied variants the dose reduction to apply is already well know, future researches are necessary to understand the role of other DPD mutations, including the c.2194G > A variant, for which interest data have been recently published.