The first enzyme in the catabolic pathway which degrades 5-FU.
It is the rate limiting step in the degradation of 5-FU and its oral prodrug capecitabine.
In the presence of a DPD deficiency 5-FU will accumulate, enabling more anabolism of 5-FU to its active metabolite.
When the excess 5-FU is anabolized, results in toxicity to malignant and normal cells.
Associated with the DYPD gene, which has several genetic variations.
4 genetic variants are associated with toxicity of 5-FU.
A partial DPD deficiency (of around 50% reduced activity) compared with normal is present in 3-5% of North American and European population.
Complete DPD deficiency has an estimated prevalence of 0.01-0.1%.
Patients with DPD deficiency have increased risk of developing severe treatment related toxicity when treated with the standard dose of fluoropyrimidimes.