Format

Send to

Choose Destination
Ann Biol Clin (Paris). 2010 Jan-Feb;68(1):27-32. doi: 10.1684/abc.2010.0394.

[Dihydropyrimidine dehydrogenase deficiency and toxicity to fluoropyrimidine].

[Article in French]

Author information

1
D├ępartement de biopathologie du cancer, Centre r├ęgional de lutte contre le cancer Paul Papin, CRCNA Inserm U892, Angers. m.boisdron@unimedia.fr

Abstract

Dihydropyrimidine dehydrogenase (DPD) is a key enzyme in the metabolic catabolism of fluoropyrimidines, such as 5-Fluorouracil and its oral prodrugs derivatives, including capecitabine and ftorafur (UFT, S1). Numerous genetic mutations have been identified in the DPD gene locus (DPYD), with a few variants having functional consequences on enzymatic activity. The allele frequency is 5% for heterozygoty and is 0.2% for homozygoty. It is correlated to the frequency of DPD activity deficiency that has been frequently reported to cause early severe, sometimes lethal fluoropyrimidine-related adverse events, regardless of the drug. Taking in account the wide and frequent use of fluoropyrimidines, both in advanced and adjuvant settings, it is clearly a problem of public healthcare that cannot be underestimated. We review in the present article the performances of assays that assess DPD and DPYD status, with an emphasis on their respective robustness and suitability for routine clinical applications. We show that DPD deficiency can be already detected primarily to treatment in practice and this detection could avoid life-threatening fluoropyrimidines toxic-side effects.

PMID:
20146975
DOI:
10.1684/abc.2010.0394
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for John Libbey Eurotext
Loading ...
Support Center