Involvement of target gene polymorphisms in 5-Fluorouracil toxicity: a case report

Pharmacology. 2012;89(1-2):99-102. doi: 10.1159/000335784. Epub 2012 Feb 15.

Abstract

Personalized medicine is becoming an important tool in oncology, both in preventing disease and in optimizing the treatment of existing cancers. Here we describe the cases of 2 patients with relevant systemic toxicity following 5-fluorouracil (5-FU) therapy and we study the more frequent polymorphisms in the target genes, in particular: (1) the variability in the number of 28-base repetitions present in the 5'-untranslated sequence of the thymidine synthase gene; (2) the presence of single-nucleotide polymorphisms in the methylene tetrahydrofolate reductase gene, and (3) the presence of mRNA splicing in intron 14 of the hepatic enzyme dihydropyrimidine dehydrogenase. The 5-FU gene profile of our patients strongly suggested that the polymorphisms expressed may contribute to the adverse effects seen during the therapy. To what extent these polymorphisms induced adverse effects cannot be established at present; however, our results strengthen the relevance of the 5-FU-related pharmacogenomic profile to predict the response outcome and the chemotherapy toxicity.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Dihydrouracil Dehydrogenase (NADP) / genetics*
  • Female
  • Fluorouracil / adverse effects*
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Polymorphism, Single Nucleotide*
  • RNA Splicing
  • Terminal Repeat Sequences
  • Thymidylate Synthase / genetics*

Substances

  • Dihydrouracil Dehydrogenase (NADP)
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Thymidylate Synthase
  • Fluorouracil