DYPD encodes dihydropyrimidine dehydrogenase (DPD), an enzyme responsible for catabolism of fluoropyrimidine. Many DPYD variants alter DPD activity in a clinically relevant manner.1,2
5-Fluorouracil and capecitabine are two widely prescribed fluoropyrimidine to treat solid tumors including colorectal and breast cancer, and cancers of the aerodigestive tract. Approximately 10-40% of patients who receive fluoropyrimidine develop severe or even fatal toxicity. Reduced activity of DPD results in reduced clearance of 5-fluorouracil and can cause dose-related toxicities. Capecitabine is a prodrug that converts to 5-fluorouracil. Therefore, decreased/no functional DPYD variant causes toxic effects on both 5-fluorouracil and capecitabine.1,2 The Clinical Pharmacogenetics Implementation Consortium (CPIC) provides recommendations on dosing of 5-fluorouracil and capecitabine by DPD phenotypes. The US Food and Drug Administration (FDA) also issues warning in the drug labels against the use of the two drugs in patient with DPD deficiency.3
Click here for the full CPIC guideline for DPYD genotype and fluoropyrimidine dosing.