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Title
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Dihydropyrimidine dehydrogenase deficiency in patients with severe toxicity after 5-fluorouracil : a retrospective single-center study
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Author
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Abstract
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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. |
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Language
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English
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Source (journal)
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Annals of gastroenterology : quarterly publication of the Hellenic Society of Gastroenterology / Hellenike Gastrenterologike Hetaireia. - Athens, Greece, 2000, currens
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Publication
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Athens, Greece
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The Society
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2020
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ISSN
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1108-7471
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DOI
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10.20524/AOG.2020.0551
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Volume/pages
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33
(2020)
, p. 1-5
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ISI
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000605685300010
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Pubmed ID
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33414624
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Full text (Publisher's DOI)
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Full text (open access)
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