Dihydropyrimidine Dehydrogenase, DPYD Full Gene Sequencing, Varies (Misc LAB000, MayoID: DPYDZ) and Dihydropyrimidine Dehydrogenase DPYD Genotype, Varies (Misc LAB000, Mayo ID:DPYDQ)

The DPYD gene encodes for dihydropyrimidine dehydrogenase, an enzyme crucial in the catabolism of these agents. Variants in this gene have been linked to slower catabolism and higher rates of toxicity.

DPYD status can be assessed either by a targeted genotyping of a panel of common polymorphisms or by full gene sequencing of the DPYD gene. Non-sequencing methods, such as the pretreatment dihydrouracil:uracil ratio, are also available but suffer from substantial intra- and inter-individual variations which make the establishment of interpretive criteria difficult.

While not yet present in formal recommendations, the NCCN and ASCO have noted that growing body of evidence in support of risk prediction using these tools prior to the initiation of treatment. Patients eligible for fluoropyrimidine therapy, such as those using 5-fluorouracil or capecitabine for solid tumor malignancies like colorectal or pancreatic cancer, should be considered for DPYD genotyping prior to initiating treatment, especially if they have a personal or family history of fluoropyrimidine toxicity.

• DPYD status is not the sole factor determining toxicity from fluoropyrimidines, so a negative test doesn’t rule out the possibility of developing medication-induced side effects.
• DPYD genotyping is an analysis of the patient’s germline DNA, thus repeat testing is not necessary.

• DPYD genotyping can provide useful information when developing chemotherapeutic strategies involving fluoropyrimidines.

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