title: Dihydropyrimidine dehydrogenase 85T>C mutation is associated with ocular toxicity of 5-fluorouracil: a case report.
abstract: 5-Fluorouracil (5-FU), the mainstay of solid tumor chemotherapy over the past 40 years, induces grade III-IV toxicities in up to 15% of patients with polymorphisms in the dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), and methylenetetrahydrofolate reductase (MTHFR) genes. These toxicities include mucositis, neutropenia, nausea, diarrhea, myelosuppression, hand-foot syndrome, and rare ocular adverse effects. Here, we present the case of a female patient with rectal cancer who received 5-FU-based chemotherapy and developed grade III hand-foot syndrome and rare acute ocular adverse effects. Genetic analysis revealed that the patient had an 85T>C mutation in the DPYD gene resulting in a DPYD*9A allele. The clinical and molecular observations indicate that DPYD deficiency may be responsible for the severe ocular adverse effects observed in 5-FU-treated patients. Application of personalized therapy based on molecular testing should help clinicians provide the most effective chemotherapy agents and dose modifications for each patient, although further population-based pharmacogenetic trials for the 5-FU metabolism-related genes are necessary to minimize adverse effects and enhance clinical outcomes.
authors.affiliation: 1Department of Basic Oncology, Institute of Oncology, Dokuz Eylul University, Izmir, Turkey; 2Department of Clinical Oncology, Ataturk University, Erzurum, Turkey; and 3Department of Clinical Oncology, Dokuz Eylul University, Izmir; Turkey.
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Baskin
authors.forename: Arsalan
authors.initials: A
authors.lastname: Amirfallah
authors.forename: Olcun Umit
authors.initials: OU
authors.lastname: Unal
authors.forename: Gizem
authors.initials: G
authors.lastname: Calibasi
authors.forename: Ilhan
authors.initials: I
authors.lastname: Oztop
mesh_terms: D000483:Alleles; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics*; D005128:Eye Diseases / Q000139:chemically induced* / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects* / Q000627:therapeutic use; D060831:Hand-Foot Syndrome / Q000209:etiology; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010597:Pharmacogenetics; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000209:etiology
chemical_list: D000964:Antimetabolites, Antineoplastic; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil