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Novel deoxycytidine kinase gene polymorphisms: a population screening study in Caucasian healthy volunteers

M Joerger1, T M Bosch, V D Doodeman

  • 1Department of Pharmacy & Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands. apmsj@slz.nl

European Journal of Clinical Pharmacology
|June 27, 2006
PubMed
Abstract

Insights

This study identified novel deoxycytidine kinase (DCK) gene variations in a Caucasian population, revealing significant inter-ethnic differences in polymorphism frequencies compared to Asian populations. These findings are crucial for understanding gemcitabine drug response.

Area of Science:

  • Pharmacogenetics
  • Molecular Biology
  • Oncology

Background:

  • Deoxycytidine kinase (DCK) is essential for activating nucleoside anticancer drugs like gemcitabine.
  • Understanding DCK genetic variations is key to predicting patient response and toxicity to these therapies.

Purpose of the Study:

  • To investigate the frequency and types of deoxycytidine kinase (DCK) polymorphisms in a predominantly Caucasian population.
  • To identify candidate DCK polymorphisms for future functional studies related to anticancer drug metabolism.

Main Methods:

  • DNA sequencing of all seven DCK exons and the promoter region in 100 healthy volunteers.
  • Analysis of genetic variations, including single nucleotide polymorphisms (SNPs), within the DCK gene.

Main Results:

  • Six novel SNPs were identified in the DCK gene, including two nonsynonymous variants (P121S and K242Q).
  • Allele frequencies of a specific promoter polymorphism (-360C>G/-201C>T) were significantly lower in Caucasians compared to previously reported data in Asians.
  • Marked inter-ethnic differences in DCK polymorphism occurrence and frequency were observed.

Conclusions:

  • The identified DCK polymorphisms, particularly the promoter variant, may contribute to inter-ethnic differences in nucleoside drug toxicity.
  • Candidate DCK SNPs from promoter, exon 3, and exon 6 will be evaluated for their impact on gemcitabine treatment efficacy.

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