5-Fluorouracil toxicity-attributable IVS14 + 1G > A mutation of the dihydropyrimidine dehydrogenase gene in Polish colorectal cancer patients

Pharmacol Rep. 2008 Mar-Apr;60(2):238-42.

Abstract

DPYD gene encodes dihydropyrimidine dehydrogenase which is the initial and rate-limiting enzyme in the metabolism of 5-fluorouracil (5-FU). The aim of our study was PCR-RFLP based-genetic testing for the most common 5-FU toxicity-attributable IVS14 + 1G > A DPYD mutation (DPYD(*)2A) in 252 Polish colorectal cancer (CRC) patients treated with this adjuvant chemotherapeutic regimen after surgery. The DPYD(*)2A allele was identified only in one patient: a male who was one of 4 CRC patients suffering from grades 3-4 myelotoxicity upon 5-FU chemotherapy. We conclude that IVS14 + 1G > A DPYD (DPYD(*)2A) variant occurs in the Polish population and is responsible for a significant proportion of life-threatening toxicity of 5-FU.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / adverse effects*
  • Antimetabolites, Antineoplastic / therapeutic use
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / genetics*
  • Dihydrouracil Dehydrogenase (NADP) / genetics*
  • Female
  • Fluorouracil / adverse effects*
  • Fluorouracil / therapeutic use
  • Gene Frequency
  • Humans
  • Male
  • Middle Aged
  • Mutation / physiology*
  • Poland / epidemiology
  • Polymorphism, Restriction Fragment Length
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Antimetabolites, Antineoplastic
  • Dihydrouracil Dehydrogenase (NADP)
  • Fluorouracil