Implications of dihydropyrimidine dehydrogenase on 5-fluorouracil pharmacogenetics and pharmacogenomics

Pharmacogenomics. 2002 Jul;3(4):485-92. doi: 10.1517/14622416.3.4.485.


A prominent example of the potential application of pharmacogenomics and pharmacogenetics to oncology is the study of dihydropyrimidine dehydrogenase (DPD) in 5-fluorouracil (5-FU) metabolism. 5-FU is currently one of the most widely administered chemotherapeutic agents used for the treatment of epithelial cancers. DPD is the rate-limiting enzyme in the catabolism and clearance of 5-FU. The observation of a familial linkage of DPD deficiency from a patient exhibiting 5-FU toxicity suggested a possible molecular basis for variations in 5-FU metabolism. Molecular studies have suggested there is a relationship between allelic variants in the DPYD gene (the gene that encodes DPD) and a deficiency in DPD activity, providing a potential pharmacogenetic basis for 5-FU toxicity. In the last decade, studies have correlated tumoral DPD activity with 5-FU response, suggesting it may be a useful pharmacogenomic marker of patient response to 5-FU-based chemotherapy. This article reviews the basis and discusses the challenges of pharmacogenetic and pharmacogenomic testing of DPD for the determination of 5-FU efficacy and toxicity.

Publication types

  • Review

MeSH terms

  • Antimetabolites, Antineoplastic / metabolism*
  • Antimetabolites, Antineoplastic / toxicity
  • Dihydrouracil Dehydrogenase (NADP)
  • Fluorouracil / metabolism*
  • Fluorouracil / toxicity
  • Genetic Markers
  • Genomics*
  • Humans
  • Oxidoreductases / genetics*
  • Oxidoreductases / metabolism
  • Pharmacogenetics*


  • Antimetabolites, Antineoplastic
  • Genetic Markers
  • Oxidoreductases
  • Dihydrouracil Dehydrogenase (NADP)
  • Fluorouracil