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• W2064670123 abstract "Purpose: Dihydropyrimidine dehydrogenase is a critical enzyme in the catabolism of 5-Fluorouracil, a drug frequently used in cancer therapy. Patients with deficient dihydropyrimidine dehydrogenase activity are at risk of developing severe 5-Fluorouracil–associated toxicity. Genetic analysis of the gene coding for dihydropyrimidine dehydrogenase has shown that mutations in exon 14, especially the splice-site mutation IVS14+1G→A, were associated with dihydropyrimidine dehydrogenase enzymatic deficiency.Methods: We evaluated the frequency of mutations in exon 14 of dihydropyrimidine dehydrogenase (DPYD) gene in 73 unselected colorectal cancer patients treated with 5-Fluorouracil after surgery at a Portuguese Cancer Institute.Results: Sequencing the entire exon 14 allowed the detection of mutations in two of the 73 patients (2.7%), namely two of the eight (25%) patients who presented grade 3-4 toxicity after 5-Fluorouracil chemotherapy. One patient was heterozygous for the splice-site mutation IVS14+1G→A, whereas the second patient was heterozygous for a novel missense mutation 1845G→T (E615D) in exon 14 of DPYD gene.Conclusion: We conclude that mutations in exon 14 of DPYD gene are responsible for a significant proportion of life-threatening toxicity to 5-Fluorouracil, and should therefore be excluded before its administration to cancer patients." @default.
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• W2064670123 date "2004-03-01" @default.
• W2064670123 modified "2023-09-27" @default.
• W2064670123 title "Mutations in exon 14 of dihydropyrimidine dehydrogenase and 5-Fluorouracil toxicity in Portuguese colorectal cancer patients" @default.
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• W2064670123 doi "https://doi.org/10.1097/01.gim.0000118061.66602.a5" @default.
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