Effects of IGF2BP2, KCNQ1 and GCKR polymorphisms on clinical outcome in metastatic gastric cancer treated with EOF regimen

Pharmacogenomics. 2015;16(9):959-70. doi: 10.2217/pgs.15.49. Epub 2015 Jun 26.

Abstract

Aim: The present study analyzed Type 2 diabetes mellitus (T2D)-related gene polymorphisms and their impacts on chemotherapeutic response and survival in patients with metastatic gastric cancer (MGC).

Patients & methods: This retrospective study enrolled 108 MGC patients treated with first-line EOF chemotherapy (epirubicin, oxaliplatin and 5-fluorouracil combination chemotherapy). Eleven single nucleotide polymorphisms of five T2D-related genes were determined.

Results: Among the 11 single nucleotide polymorphisms, three (IGF2BP2 rs4402960, IGF2BP2 rs6769511 and KCNQ1 rs163182) were significantly associated with disease control rate and two (GCKR rs780093 and rs780094) were significantly associated with progression-free and overall survival.

Conclusion: Our results suggest IGF2BP2 and KCNQ1 polymorphisms might be independent predictors of chemotherapeutic response, while GCKR polymorphisms might be independent predictors of survival in MGC patients treated with first-line EOF chemotherapy. Original submitted 30 June 2014; revision submitted 15 April 2015.

Keywords: GCKR; IGF2BP2; KCNQ1; biomarker; chemotherapy; gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Disease-Free Survival
  • Epirubicin / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Genotype
  • Humans
  • KCNQ1 Potassium Channel / genetics*
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Polymorphism, Single Nucleotide / genetics
  • Predictive Value of Tests
  • RNA-Binding Proteins / genetics*
  • Retrospective Studies
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics*
  • Survival Analysis
  • Treatment Outcome
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • GCKR protein, human
  • IGF2BP2 protein, human
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • Organoplatinum Compounds
  • RNA-Binding Proteins
  • Oxaliplatin
  • Epirubicin
  • Fluorouracil