Background: Fluoropyrimidines are widely used in the treatment of solid tumors and remain the backbone
of many combination chemotherapy regimens. Despite their clinical benefit, they are associated with frequent
gastrointestinal and hematological toxicities, which often lead to treatment discontinuation. Fluoropyrimidines
undergo complex anabolic and catabolic biotransformation. Enzymes involved in this pathway include
dihydropyrimidine dehydrogenase (DPD), which breaks down 5-FU and its prodrugs. Candidate gene approaches
have demonstrated associations between 5-FU treatment outcomes and germline polymorphisms in
DPD. The aim of this review is to report and discuss the latest results on fluoropyrimidine pharmacogenetics.
Methods: Literature from PubMed databases and bibliography from retrieved publications have been analyzed
according to terms such DPD, DPYD, fluoropyrimdines, polymorphisms, toxicity, pharmacogenetics.
Results: To date, many sequence variations have been identified within DPYD gene, although the majority of
these have no functional consequences on enzymatic activity. Nowadays, there is a general agreement on the
clinical significance of the importance of DPD deficiency in patients who suffer from severe, life-threatening
drug toxicity although preemptive testing is not applied to all patients.
Conclusion: Considering the published literature, clinicians are strongly encouraged to consider testing for DPD
poor metabolizer variants as a rational pre-treatment screening for patients candidate to a fluoropyrimidine-based
regimens, in order to prevent toxicities and personalise treatments.