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Identification and analysis of single-nucleotide polymorphisms in the gemcitabine pharmacologic pathway
A K Fukunaga1, S Marsh, D J Murry
1Department of Clinical Pharmacy and Pharmacy Practice, Purdue University, W. Lafayette, IN, USA.
The Pharmacogenomics Journal
|June 30, 2004
Summary
Researchers identified genetic variations, called single-nucleotide polymorphisms (SNPs), in genes affecting gemcitabine drug metabolism. These findings are a first step toward predicting patient responses and toxicity to this important cancer therapy.
Area of Science:
- Pharmacogenomics
- Cancer Therapeutics
- Molecular Biology
Background:
- Gemcitabine exhibits variable antitumor efficacy and systemic toxicity in cancer patients.
- Currently, no tools exist for prospectively identifying patients at risk of adverse events associated with gemcitabine treatment.
Purpose of the Study:
- To identify and validate single-nucleotide polymorphisms (SNPs) within genes crucial for gemcitabine metabolism and transport.
- To establish a foundation for predicting individual patient responses and toxicity to gemcitabine therapy.
Main Methods:
- Database mining was employed to identify SNPs in 14 genes associated with gemcitabine metabolism.
- Pyrosequencing was used to determine SNP allele frequencies in genomic DNA from European and African populations (n=190).
Main Results:
- A total of 14 genetic variants, including 12 SNPs, were identified in eight gemcitabine metabolic pathway genes.
- Significant differences in allele frequencies were observed for nine of the 14 analyzed polymorphisms between European and African populations (P<0.05).
Conclusions:
- This study represents a foundational step in identifying genetic markers for predicting variability in gemcitabine response and toxicity.
- The identified SNPs and population-specific frequency differences offer potential targets for future pharmacogenomic studies aimed at personalizing gemcitabine treatment.