Fluorouracil (5-FU) and DPD Enzyme Deficiency
Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the degradation of pyrimidine bases like thymidine and uracil. DPD is also the main enzyme involved in the degradation of structurally related compounds like 5-Fluorouracil (5-FU), a widely used anticancer drug. In 5-FU-based cancer chemotherapy, severe toxicities are observed at higher rates in patients who are heterozygous for a mutant DPYD allele, compared with toxicities in patients who are homozygous for the wild DPYD allele. The adverse effects of 5-FU are often lethal for patients homozygous for the mutant DPYD allele. On the basis of catalytic activity, and on the basis of the mutation frequency, a 3% frequency for heterozygotes (-/+) to DPD was predicted, projecting a 1:1000 homozygotes (+/+) for this mutation across racial lines. Who Should Be TestedThe DPD test for 5-FU is considered appropriate for any person who is taking or considering 5-FU based chemotherapy.It is recommended that this screening be accompanied by direct measurement of DPD activity prior to 5-FU treatment in cancer patients. Although this test looks for the most frequent genetic variation that causes DPD enzyme deficiency this does not rule out the possibility of a decrease in DPD activity due to other factors or genetic variations. Ordering TestsNow you can add another dimension to providing safer and more efficacious care to your patients by ordering DNA Drug Sensitivity Testing™ for them. Call (800) 523-3080 for more information or to obtain collection kits, or visit how to order for test requisition forms and sample requirements.
importance and molecular basis of dihydropyrimidine dehydrogenase deficiency. Trends Pharmacol. Sci. 16:325-327. van Kuilenburg AB, Vreken P, Beex LV, De Abreu RA, van Gennip AH. Wei, X., McLeod, HL., et al.(1996) Molecular basis of the human McMurrough, J. and McLeod, H.L. (1996) Analysis of the dihydropyrimidine Disclaimer: The content on this page is intended for healthcare professionals.
By Kristine Ashcraft, B.S. Last Reviewed 8/20/10
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