Effect of transporter and DNA repair gene polymorphisms to lung cancer chemotherapy toxicity

Tumour Biol. 2016 Feb;37(2):2275-84. doi: 10.1007/s13277-015-4048-0. Epub 2015 Sep 11.

Abstract

Lung cancer is the first leading cause of cancer deaths. Chemotherapy toxicity is one of factors that limited the efficacy of platinum-based chemotherapy in lung cancer patients. Transporters and DNA repair genes play critical roles in occurrence of platinum-based chemotherapy toxicity. To investigate the relationships between transporter and DNA repair gene polymorphisms and platinum-based chemotherapy toxicity in lung cancer patients, we selected 60 polymorphisms in 14 transporters and DNA repair genes. The polymorphisms were genotyped in 317 lung cancer patients by Sequenom MassARRAY. Logistic regression was performed to estimate the association of toxicity outcome with the polymorphisms by PLINK. Our results showed that polymorphisms of SLC2A1 (rs3738514, rs4658, rs841844) were significantly related to overall toxicity. XRCC5 (rs1051685, rs6941) and AQP2 (10875989, rs3759125) polymorphisms were associated with hematologic toxicity. AQP2 polymorphisms (rs461872, rs7305534) were correlated with gastrointestinal toxicity. In conclusion, genotypes of these genes may be used to predict the platinum-based chemotherapy toxicity in lung cancer patients.

Keywords: Chemotherapy toxicity; DNA repair gene; Genetic polymorphism; Lung cancer; Platinum; Transporter.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Aquaporin 2 / genetics*
  • DNA Repair / genetics
  • Female
  • Genotype
  • Glucose Transporter Type 1 / genetics*
  • Humans
  • Ku Autoantigen / genetics*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Male
  • Membrane Transport Proteins / genetics
  • Middle Aged
  • Polymorphism, Single Nucleotide*

Substances

  • AQP2 protein, human
  • Antineoplastic Agents
  • Aquaporin 2
  • Glucose Transporter Type 1
  • Membrane Transport Proteins
  • SLC2A1 protein, human
  • XRCC5 protein, human
  • Ku Autoantigen