Increased risk of grade IV neutropenia after administration of 5‐fluorouracil due to a dihydropyrimidine dehydrogenase deficiency: High prevalence of the IVS14+1g>a mutation

摘要: Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in catabolism of 5-fluorouracil (5-FU), it suggested that patients with a partial deficiency this are at risk developing severe 5-FU-associated toxicity. We evaluated importance DPD deficiency, gender presence IVS14+1G>A mutation etiology 5-FU In 61% cases, decreased activity could be detected peripheral blood mononuclear cells. Furthermore, number females (65%) total group appeared to higher than males (35%) (p = 0.03). Patients have 3.4-fold grade IV neutropenia normal activity. Analysis DPYD gene suffering from for showed 50% investigated were heterozygous or homozygous mutation. Adopting threshold level 70% observed population, 14% population prone development Below level, 90% individuals can identified. Considering common use treatment cancer, 5-FU-related toxicities low apparently high prevalence mutation, screening before administration warranted.