Dihydropyrimidine dehydrogenase deficiency in patients with severe toxicity after 5-fluorouracil: A retrospective single-center study

Stephanie Detailleur, Eva Segelov, Marzia Del Re, Hans Prenen

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Background 5-Fluorouracil (5-FU) is an agent frequently used in the treatment of solid cancers. A deficiency in the enzyme that catabolizes 5-FU leads to severe toxicity. The gene responsible for this enzyme is DPYD, located on chromosome 1q22. The most prevalent alteration described is DPYD*2A, which leads to a splicing defect and thus skipping of the translation of an entire exon. The objectives of this retrospective study were to describe the frequencies of DPYD gene mutations in a Belgian population and to correlate them with the grade of toxicity. Methods This was a retrospective, single-center study conducted at the University Hospitals Leuven, by reviewing a database of patients screened for DPYD gene mutations between May 2009 and June 2015 after prolonged grade 3-4 toxicity. Polymerase chain reaction sequencing of exons 2, 6, 10, 11, 13, 18, 19 and 22, and pyrosequencing of exon 14 were performed by an in-house laboratory. Results Of the 80 patients screened, 65 were heterozygous or compound heterozygous for DPYD and 3 had a homozygous mutation. The most prevalent mutation in our population was DPYD*9A. Conclusions Despite previous reports, in our small retrospective study the most prevalent variation in patients with severe adverse events was DPYD*9A. As this variant has previously been reported to be benign, we suggest that screening for dihydropyrimidine dehydrogenase deficiency should be extended across multiple exons of the DPYD gene.

Original languageEnglish
Pages (from-to)68-72
Number of pages5
JournalAnnals of Gastroenterology
Issue number1
Publication statusPublished - 2021


  • 5-fluorouracil
  • Deficiency
  • Dihydropyrimidine dehydrogenase
  • Toxicity

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