Relationship between deoxycytidine kinase (DCK) genotypic variants and fludarabine toxicity in patients with follicular lymphoma

Leuk Res. 2011 Apr;35(4):431-7. doi: 10.1016/j.leukres.2010.09.026. Epub 2010 Oct 27.

Abstract

DCK catalyzes the intracellular phosphorylation of fludarabine. The promoter and coding region of the DCK gene were analyzed in 74 follicular lymphoma (FL) patients receiving a therapeutic regimen that included fludarabine. DCK mRNA expression was quantified in a cohort of healthy donors. Four previously described genotypic variants, -360C>G, -201C>T (rs2306744), C28624T (rs11544786) and c.91+37G>C (rs9997790), as well as the new variant, -12C>G, were identified. Variant C28624T showed a lower risk of lymphopenia (P=0.04), but a higher risk of neutropenia (P=0.04). Statistical significance was found in bivariate logistic regression between lymphopenia and infectious episodes in the induction period (odds ratio 3.85, P=0.04).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cohort Studies
  • DNA Mutational Analysis
  • Deoxycytidine Kinase / genetics*
  • Drug-Related Side Effects and Adverse Reactions / genetics
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Leukemic
  • Gene Frequency
  • Genotype
  • Humans
  • Kaplan-Meier Estimate
  • Logistic Models
  • Lymphoma, Follicular / drug therapy
  • Lymphoma, Follicular / genetics*
  • Lymphopenia / chemically induced
  • Neutropenia / chemically induced
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Treatment Outcome
  • Vidarabine / administration & dosage
  • Vidarabine / adverse effects
  • Vidarabine / analogs & derivatives

Substances

  • Deoxycytidine Kinase
  • Vidarabine
  • fludarabine