Linked Life Data

12360106

Source:http://linkedlifedata.com/resource/pubmed/id/12360106

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2002-10-2
pubmed:abstractText
Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-fluorouracil (5FU) and a DPD deficiency is increasingly being recognized as an important pharmacogenetic factor in the aetiology of severe 5FU-associated toxicity. In this study, we evaluated the DPD activity and the prevalence of the common splice site mutation IVS14 + 1G>A in tumour patients suffering from severe grade 3-4 toxicity after the administration of 5FU. DPD activity was measured with a radiochemical assay and screening for the presence of the IVS14 + 1G>A mutation was performed by restriction fragment length polymorphism. A decreased DPD activity could be detected in peripheral blood mononuclear cells in 60% of the cases. Furthermore, a high prevalence of the IVS14 + 1G>A mutation was noted as 28% of all patients were heterozygous or homozygous for this mutation. In patients with a low DPD activity, 42% were heterozygous and one patient (3%) was homozygous for the IVS14 + 1G>A mutation. In contrast, the IVS14 + 1G>A mutation could be detected in only one out of 24 (4%) patients with a normal DPD activity. Our study demonstrates that a DPD deficiency is the major determinant of 5FU-associated toxicity. The apparently high prevalence of the IVS14 + 1G>A mutation warrants genetic screening for this mutation in cancer patients before the administration of 5FU.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0960-314X
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
555-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
High prevalence of the IVS14 + 1G>A mutation in the dihydropyrimidine dehydrogenase gene of patients with severe 5-fluorouracil-associated toxicity.
pubmed:affiliation
Academic Medical Center, University of Amsterdam, Emma Children's Hospital and Department of Clinical Chemistry, Amsterdam, The Netherlands. a.b.vanKuilenburg@amc.uva.nl
pubmed:publicationType
Journal Article