Cytidine Deaminase as a Molecular Predictor of Gemcitabine Response in Patients with Biliary Tract Cancer

Oncology. 2015;89(6):345-50. doi: 10.1159/000439222. Epub 2015 Sep 30.

Abstract

Objective: Gemcitabine-based chemotherapy is regarded as the standard treatment for biliary tract cancer (BTC). Potential biomarkers for gemcitabine response include the activities of cytidine deaminase (CDA), human equilibrative nucleoside transporter 1 (hENT1), deoxycytidine kinase (DCK), and ribonucleotide reductase M1 (RRM1). Here, we investigated whether single nucleotide polymorphisms (SNPs) in their encoding genes were associated with the efficacy of gemcitabine chemotherapy in treating BTC.

Methods: We retrospectively evaluated 11 SNPs in the CDA, hENT1, DCK, human concentrative nucleoside transporter 3 (hCNT3), and RRM1 genes in 80 patients with unresectable, metastatic, or recurrent BTC who were treated with gemcitabine plus cisplatin.

Results: After the results were adjusted for clinical predictors, the variant allele of rs1048977 in the CDA gene was associated with tumor response in a dominant model (OR, 0.23; 95% CI, 0.06-0.93; p = 0.039). No significant association was detected between the 11 SNPs and grade 3/4 toxicity.

Conclusions: Our findings suggest that the polymorphism of CDA may be a potential predictive marker for the efficacy of gemcitabine-based chemotherapy in patients with BTC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biliary Tract Neoplasms / drug therapy
  • Biliary Tract Neoplasms / genetics*
  • Biliary Tract Neoplasms / mortality
  • Biliary Tract Neoplasms / pathology
  • Biomarkers, Tumor / genetics*
  • Cisplatin / administration & dosage
  • Cytidine Deaminase / genetics*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine Kinase / genetics
  • Equilibrative Nucleoside Transporter 1 / genetics
  • Female
  • Follow-Up Studies
  • Gemcitabine
  • Humans
  • Lymphatic Metastasis
  • Male
  • Membrane Transport Proteins / genetics
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Retrospective Studies
  • Ribonucleoside Diphosphate Reductase
  • Survival Rate
  • Tumor Suppressor Proteins / genetics

Substances

  • Biomarkers, Tumor
  • Equilibrative Nucleoside Transporter 1
  • Membrane Transport Proteins
  • SLC29A1 protein, human
  • Tumor Suppressor Proteins
  • cif nucleoside transporter
  • Deoxycytidine
  • RRM1 protein, human
  • Ribonucleoside Diphosphate Reductase
  • Deoxycytidine Kinase
  • Cytidine Deaminase
  • Cisplatin
  • Gemcitabine