Oncologie

, Volume 16, Issue 2–3, pp 96–102 | Cite as

La dihydropyrimidine déshydrogénase (DPD)

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Résumé

La dihydropyrimidine déshydrogénase (DPD) est l’enzyme clé du catabolisme de la famille des fluoropyrimidines. Son activité dans la population générale suit une courbe de Gauss, et elle est soumise à un polymorphisme génétique qui peut avoir des répercussions fonctionnelles, c’est-à-dire entraîner des déficits majeurs à l’origine de toxicité grave chez 2 à 5 % des patients traités. La sévérité de ces toxicités aiguës fait de leur prévention une priorité médicale et de santé publique. Différentes approches ont été évaluées, et la combinaison de deux techniques complémentaires, de génotypage et de phénotypage, nous apparaît indispensable pour la détection fiable d’un déficit en DPD en pratique courante et la prévention de toxicités sévères liées aux fluoropyrimidines.

Mots clés

5-fluoro-uracile Fluoropyrimidines Déficit en dihydropyrimidine déshydrogénase Toxicité Pharmacogénétique SNP Pharmacocinétique 

Dihydropyrimidine Dehydrogenase (DPD)

Abstract

Dihydropyrimidine dehydrogenase (DPD) is a key enzyme in the catabolism of fluoropyrimidines. Its activity follows a Gaussian curve in the general population and some mutations have been identified in the gene reported to cause early severe related adverse events, in 2 to 5% of the patients. It is clearly a problem of public healthcare that cannot be underestimated. We review the performances of assays that assess DPD status. The combination of 2 complementary techniques, genotyping and enzyme phenotyping, suitable for routine clinical applications is crucial for reliably detecting DPD deficiency and avoiding early severe toxicity associated with fluoropyrimidines.

Keywords

Dehydropyrimidine dehydrogenase Fluoropyrimidine DPD deficiency Gene sequencing Toxicity 

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Copyright information

© Springer-Verlag France 2014

Authors and Affiliations

  1. 1.Inserm U892, département d’oncopharmacologie-pharmacogénétique, institut de cancérologie de l’Ouestcentre régional de lutte contre le cancer Paul-PapinAngersFrance

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