Mutations in exon 14 of dihydropyrimidine dehydrogenase and 5-Fluorouracil toxicity in Portuguese colorectal cancer patients

• Type: Article in International Scientific Journal
• Date: 2004

Authors

Salgueiro, N (Author) Other; Veiga, I (Author) Other; Fragoso, M (Author) Other; Sousa, O (Author) Other; Costa, N (Author) Other; Pellon, ML (Author) Other; Sanches, E (Author) Other; dos Santos, JG (Author) Other; Manuel R Teixeira (Author) ICBAS; CASTEDO, S (Author) FMUP

Journal

Title: Genetics in Medicine

Vol. 6

Pages: 102-107

ISSN: 1098-3600

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 25 Citations

Scopus - 30 Citations

Other information

Authenticus ID: P-000-BCQ

DOI: 10.1097/01.gim.0000118061.66602.a5

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6