title: Involvement of target gene polymorphisms in 5-Fluorouracil toxicity: a case report.
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.
authors.affiliation: Division of Oncology, AO Spedali Civili, University of Brescia Medical School, Brescia, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Scalvini
authors.forename: Vittorio
authors.initials: V
authors.lastname: Ferrari
authors.forename: Serena
authors.initials: S
authors.lastname: Bodei
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Arcangeli
authors.forename: Francesca
authors.initials: F
authors.lastname: Consoli
authors.forename: PierFranco
authors.initials: P
authors.lastname: Spano
authors.forename: Sandra
authors.initials: S
authors.lastname: Sigala
mesh_terms: D000328:Adult; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012326:RNA Splicing; D020079:Terminal Repeat Sequences; D013940:Thymidylate Synthase / Q000235:genetics*
chemical_list: D042943:Dihydrouracil Dehydrogenase (NADP); D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013940:Thymidylate Synthase; D005472:Fluorouracil