Identification and analysis of single-nucleotide polymorphisms in the gemcitabine pharmacologic pathway

A. K. Fukunaga, S. Marsh, Daryl J Murry, T. D. Hurley, H. L. McLeod

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Significant variability in the antitumor efficacy and systemic toxicity of gemcitabine has been observed in cancer patients. However, there are currently no tools for prospective identification of patients at risk for untoward events. This study has identified and validated single-nucleotide polymorphisms (SNP) in genes involved in gemcitabine metabolism and transport Database mining was conducted to identify SNPs in 14 genes involved in gemcitabine metabolism. Pyrosequencing was utilized to determine the SNP allele frequencies in genomic DNA from European and African populations (n = 190). A total of 14 genetic variants (including 12 SNPs) were identified in eight of the gemcitabine metabolic pathway genes. The majority of the database variants were observed in population samples. Nine of the 14 (64%) polymorphisms analyzed have allele frequencies that were found to be significantly different between the European and African populations (P<0.05) This study provides the first step to identify markers for predicting variability in gemcitabine response and toxicity.

Original languageEnglish (US)
Pages (from-to)307-314
Number of pages8
JournalPharmacogenomics Journal
Volume4
Issue number5
DOIs
StatePublished - Oct 20 2004

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gemcitabine
Single Nucleotide Polymorphism
Gene Frequency
Databases
Population
Genes
Metabolic Networks and Pathways
DNA

Keywords

  • Drug pathway
  • Gemcitabine
  • Pharmacogenetics
  • Pyrosequencing

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine
  • Genetics

Cite this

Identification and analysis of single-nucleotide polymorphisms in the gemcitabine pharmacologic pathway. / Fukunaga, A. K.; Marsh, S.; Murry, Daryl J; Hurley, T. D.; McLeod, H. L.

In: Pharmacogenomics Journal, Vol. 4, No. 5, 20.10.2004, p. 307-314.

Research output: Contribution to journalArticle

Fukunaga, A. K. ; Marsh, S. ; Murry, Daryl J ; Hurley, T. D. ; McLeod, H. L. / Identification and analysis of single-nucleotide polymorphisms in the gemcitabine pharmacologic pathway. In: Pharmacogenomics Journal. 2004 ; Vol. 4, No. 5. pp. 307-314.
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