Dihydropyrimidine dehydrogenase

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.

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