Selected Variants (Mutant Allele, Enzyme Activity)
DPYD*2A (1905+1G>A, none);
DPYD*13 (1679T>G, ↓↓);
DPYD rs67376798 (2846A>T, ↓↓)
These non-functional variants are present in 0.1–1% of whites (eg, French Caucasians)
5-fluorouracil (5-FU), capecitabine (Xeloda)
Fluoropyrimidines (ie, 5-fluorouracil, capecitabine) are metabolized by dihydropyrimidine dehydrogenase (DPD) enzyme, encoded by the DPYD gene. To avoid severe or even fatal drug toxicity, an alternative drug should be selected for patients who are homozygous for DPYD non-functional variants (*2A, *13, or rs67376798). Consider a 50% reduction in starting dose for heterozygous patients who have low DPD activity (30–70% of normal).
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