Dihydropyrimidine dehydrogenase pharmacogenetics in patients with colorectal cancer.
Article Details
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Ridge SA, Sludden J, Wei X, Sapone A, Brown O, Hardy S, Canney P, Fernandez-Salguero P, Gonzalez FJ, Cassidy J, McLeod HL
Dihydropyrimidine dehydrogenase pharmacogenetics in patients with colorectal cancer.
Br J Cancer. 1998;77(3):497-500.
- PubMed ID
- 9472650 [ View in PubMed]
- Abstract
Individuals with a deficiency in the enzyme dihydropyrimidine dehydrogenase (DPD) may experience severe life-threatening toxicity when treated with 5-fluorouracil (5-FU). As routine measurement of enzyme activity is not practical in many clinical centres, we have investigated the use of DNA mutation analysis to identify cancer patients with low enzyme levels. We have identified two new mutations at codons 534 and 543 in the DPD cDNA of a patient with low enzyme activity and screened the DNA from 75 colorectal cancer patients for these mutations and the previously reported splice site mutation (Vreken et al, 1996; Wei et al, 1996). In all cases, DPD enzyme activity was also measured. The splice site mutation was detected in a patient (1 out of 72) with low enzyme activity whereas mutations at codons 534 (2 out of 75) and 543 (11 out of 23) were not associated with low enzyme activity. These studies highlight the need to combine DPD genotype and phenotype analysis to identify mutations that result in reduced enzyme activity.