DPYD (DPD) Genotyping

The DPYD gene encodes an enzyme known as dihydropyrimidine dehydrogenase (DPYD). This enzyme is critical to the metabolism of fluoropyrimidine drugs such as fluorouracil/5-FU (Adrucil®) and capecitabine (Xeloda®) .[46] These drugs are all part of chemotherapy treatments for many cancers including head and neck, gastrointestinal and colorectal cancers. The DPYD gene is also the rate-limiting step in the breakdown of pyrimidines, such as uracil and thymine. Mutations, or variations, in DPYD are known to cause severe 5-FU toxicity as a result of decreased DPYD activity.

Genetic variants tested for DPYD are *2,*13, c.2846A>T

Indications for DPYD Testing

Patients who are candidates for fluorouracil or capecitabine therapy should be considered for DPYD genotyping prior to starting their treatment regimen, especially if the patients have a personal or family history of 5-FU toxicity. All three DPYD metabolizer phenotypes carry a clinically actionable recommendation for treatment and dosing.