Two cases of 5-fluorouracil toxicity linked with gene variants in the DPYD gene
2010 (English)In: CLINICAL BIOCHEMISTRY, ISSN 0009-9120, Vol. 43, no 3, 331-334 p.Article in journal (Refereed) Published
Objectives: Dihydropyrimidine dehydrogenase (DPD) is the initial rate-limiting enzyme in endogenous pyrimidine catabolism and is responsible for the reduction of the pyrimidine analog 5-fluorouracil (5-FU). DPD deficiency is known to cause potentially lethal toxicity in patients receiving 5-FU. We here report a frequency analysis of one of the major splice-site mutations in the DPDY gene, and further two new DPYD gene variants. Design and methods: Restriction fragment length polymorphisin (RFLP) and DNA sequence analysis were performed on genomic DNA and mRNA. Results: In 400 patients that were diagnosed with cancer and were eligible for 5-FU treatment, 14 patients were found to be heterozygous for the splice-site mutation DPYD IVS14+1Gandgt;A, which corresponds to a population frequency of 3.5%. Two novel variants in the DPYD gene were identified. The first case was heterozygous for DPYD c. 1796Tandgt;C (p.M599T). In the second case, we observed heterozygosity for the splice-site mutation DPYD IVS14+17Aandgt;G. Conclusions: We report two new DPYD gene variants, of which DPYD c. 1796Tandgt;C is potentially pathogenic, whereas DPYD IVS14+17Aandgt;G is suggested as a variant without clinical significance.
Place, publisher, year, edition, pages
2010. Vol. 43, no 3, 331-334 p.
Dihydropyrimidine dehydrogenase, DPYD, 5-fluorouracil, Toxicity, Colon cancer
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-54076DOI: 10.1016/j.clinbiochem.2009.09.024ISI: 000274104000021OAI: oai:DiVA.org:liu-54076DiVA: diva2:298292
Original Publication: Anna Ofverholm, Eva Arkblad, Stanko Skrtic, Per Albertsson, Emman Shubbar and Charlotta Enerbäck, Two cases of 5-fluorouracil toxicity linked with gene variants in the DPYD gene, 2010, CLINICAL BIOCHEMISTRY, (43), 3, 331-334. http://dx.doi.org/10.1016/j.clinbiochem.2009.09.024 Copyright: Elsevier Science B.V., Amsterdam. http://www.elsevier.com/2010-02-222010-02-222013-04-02