Journal
PHARMACOGENOMICS JOURNAL
Volume 4, Issue 5, Pages 307-314Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.tpj.6500259
Keywords
gemcitabine; drug pathway; pyrosequencing; pharmacogenetics
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Funding
- NCI NIH HHS [P30 CA091842] Funding Source: Medline
- NIGMS NIH HHS [U01 GM63340] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [P30CA091842] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [U01GM063340] Funding Source: NIH RePORTER
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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.
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