title: Dihydropyrimidine dehydrogenase activity and the IVS14+1G>A mutation in patients developing 5FU-related toxicity.
abstract: OBJECTIVE
  To examine retrospectively the relationship between DPD phenotype/genotype and the intensity of 5FU toxicity.
  
  
  METHODS
  One hundred and thirty-one case-reports (81 women, 50 men) with 5FU-related toxicity were analyzed.
  
  
  RESULTS
  The lower the DPD activity (10-504 pmol min(-1) mg(-1)), the higher the toxicity grade was scored (P < 0.01). Toxicity-related deaths occurred in nine patients (eight women) who significantly expressed lower DPD activity than other patients. Two of the deceased patients had normal DPD activity. The IVS14+1G>A mutation, analyzed in 93 patients, was detected in two patients (nonlethal toxicity).
  
  
  CONCLUSIONS
  The IVS14+1G>A mutation may not help prevent toxicity and patients with normal DPD activity may develop life-threatening 5FU toxicity.
authors.affiliation: Institut Gustave Roussy, Villejuif, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Magné
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Etienne-Grimaldi
authors.forename: Laurent
authors.initials: L
authors.lastname: Cals
authors.forename: Nicole
authors.initials: N
authors.lastname: Renée
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Formento
authors.forename: Mireille
authors.initials: M
authors.lastname: Francoual
authors.forename: Gérard
authors.initials: G
authors.lastname: Milano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000187:drug effects*; D011110:Polymorphism, Genetic
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil