DPD 5-Fluorouracil Toxicity

Whole blood or LabCorp buccal swab kit (buccal swab collection kit contains instructions for use of a buccal swab)

7 mL whole blood or LabCorp buccal swab kit

3 mL whole blood or two buccal swabs

Lavender-top (EDTA) tube, yellow-top (ACD) tube, or LabCorp buccal swab kit

Variability in response (efficacy and toxicity) to 5-fluorouracil (5-FU) chemotherapy has been linked to the rate-limiting enzyme in the drug's catabolic pathway, known as dihydropyrimidine dehydrogenase (DPD).

This procedure will only detect the presence of the wild type or mutant allele for the DPD IVS14+1G>A mutation.

Polymerase chain reaction (PCR); restriction enzyme digestion; gel electrophoresis

DPD deficiency results in excessive amounts of 5-FU available to be anabolized to its active metabolite and is relatively undetectable by clinical observation prior to 5-FU administration. Extensive studies have associated both profound and partial deficiency in DPD activity with severe unanticipated toxicity after 5-FU administration. Numerous studies genotyping DPD deficient patients, their family members, and healthy individuals have shown that the splice-site mutation (IVS14+1G>A) is the most characterized and frequently observed allele associated with decreased DPD enzyme activity. Screening for the presence of this mutation in the Caucasian population showed frequencies of 0.91% homozygous and 1.8% heterozygous for the IVS14+1G>A allele.