Linked Life Data

11555601

Source:http://linkedlifedata.com/resource/pubmed/id/11555601

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2001-9-13
pubmed:abstractText
Deficiency of dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme in 5-fluorouracil (5-FU) catabolism, has been linked to toxic side effects of 5-FU. The most prominent mutation of the DPD gene resulting in severe DPD deficiency is a G to A mutation in the GT 5'-splice recognition site of intron 14 (exon 14-skipping mutation). The corresponding mRNA lacks exon 14, and the enzymatic activity of the translated DPD protein is virtually absent. We developed a reverse transcription-PCR-based assay suitable for routine identification of the exon 14-skipping mutation and screened a control cohort of 851 Caucasian individuals as well as a cohort of 25 cancer patients reported by their physicians to have suffered from WHO grades 3-4 toxicity upon 5-FU chemotherapy. Within the control cohort, in total, eight heterozygotes were detected (0.94%): one heterozygote in 51 healthy donors, (1.96%); five heterozygotes in 572 hospital patients (0.87%); and two heterozygotes in 228 colorectal tumor patients (0.88%). Among the 25 patients with severe 5-FU-related toxicity, 5 (20%) were heterozygous and 1 (4%) was homozygous for the exon 14-skipping mutation. All six patients had experienced WHO grade 4 myelosuppression. Lethal outcome was seen in the homozygous and two of the heterozygous cases. We conclude that carriers of the DPD exon 14-skipping mutation are at significantly increased risk to experience life-threatening myelosuppression upon 5-FU treatment, even when the allelic status is heterozygous. These data lead us to suggest routine testing for the exon 14-skipping mutation before 5-FU treatment.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2832-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11555601-Adult, pubmed-meshheading:11555601-Aged, pubmed-meshheading:11555601-Alternative Splicing, pubmed-meshheading:11555601-Antimetabolites, Antineoplastic, pubmed-meshheading:11555601-Breast Neoplasms, pubmed-meshheading:11555601-Colonic Neoplasms, pubmed-meshheading:11555601-DNA, Complementary, pubmed-meshheading:11555601-Diarrhea, pubmed-meshheading:11555601-Dihydrouracil Dehydrogenase (NADP), pubmed-meshheading:11555601-Exons, pubmed-meshheading:11555601-Female, pubmed-meshheading:11555601-Fluorouracil, pubmed-meshheading:11555601-Gene Frequency, pubmed-meshheading:11555601-Genotype, pubmed-meshheading:11555601-Heterozygote, pubmed-meshheading:11555601-Homozygote, pubmed-meshheading:11555601-Humans, pubmed-meshheading:11555601-Introns, pubmed-meshheading:11555601-Leukopenia, pubmed-meshheading:11555601-Male, pubmed-meshheading:11555601-Middle Aged, pubmed-meshheading:11555601-Oxidoreductases, pubmed-meshheading:11555601-Point Mutation, pubmed-meshheading:11555601-Rectal Neoplasms, pubmed-meshheading:11555601-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11555601-Severity of Illness Index, pubmed-meshheading:11555601-Stomach Neoplasms, pubmed-meshheading:11555601-Stomatitis, pubmed-meshheading:11555601-Thrombocytopenia
pubmed:year
2001
pubmed:articleTitle
Prevalence of a common point mutation in the dihydropyrimidine dehydrogenase (DPD) gene within the 5'-splice donor site of intron 14 in patients with severe 5-fluorouracil (5-FU)- related toxicity compared with controls.
pubmed:affiliation
Department of Internal Medicine II, Friedrich-Schiller-Universität Jena, D-07740 Jena, Germany. m.raida@icrf.icnet.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't