Dihydropyrimidine dehydrogenase 85T>C mutation is associated with ocular toxicity of 5-fluorouracil: a case report

• Published in: American journal of therapeutics Vol. 22; no. 2; p. e36
• Main Authors: Baskin, Yasemin, Amirfallah, Arsalan, Unal, Olcun Umit, Calibasi, Gizem, Oztop, Ilhan
• Format: Journal Article
• Language: English
• Published: United States 01.03.2015
• Subjects: Alleles; Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - therapeutic use; Dihydrouracil Dehydrogenase (NADP) - genetics; Eye Diseases - chemically induced; Eye Diseases - genetics; Female; Fluorouracil - adverse effects; Fluorouracil - therapeutic use; Hand-Foot Syndrome - etiology; Humans; Middle Aged; Mutation; Pharmacogenetics; Rectal Neoplasms - drug therapy; Rectal Neoplasms - etiology
• ISSN: 1536-3686
• DOI: 10.1097/MJT.0b013e31829e8516

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.