Contributory role of five common polymorphisms of RAGE and APE1 genes in lung cancer among Han Chinese

PLoS One. 2013 Jul 11;8(7):e69018. doi: 10.1371/journal.pone.0069018. Print 2013.


Background: Lung cancer is the leading cause of cancer mortality in China. Given the ubiquitous nature of gene-to-gene interaction in lung carcinogenesis, we sought to evaluate five common polymorphisms from advanced glycosylation end product-specific receptor (RAGE) and apurinic/apyrimidinic endonuclease 1 (APE1) genes in association with lung cancer among Han Chinese.

Methods and results: 819 patients with lung cancer and 803 cancer-free controls were recruited from Qiqihar city. Genotypes of five examined polymorphisms (RAGE gene: rs1800625, rs1800624, rs2070600; APE1 gene: rs1760944, rs1130409) were determined by ligase detection reaction method. Data were analyzed by R software and multifactor dimensionality reduction (MDR). Hardy-Weinberg equilibrium was satisfied for all five polymorphisms. Overall differences in the genotype and allele distributions were significant for rs1800625 (Pgenotype<0.0005; Pallele<0.0005), rs2070600 (Pgenotype = 0.005; Pallele = 0.004) and rs1130409 (Pgenotype = 0.009; Pallele = 0.004) polymorphisms. Haplotype C-A-A (alleles in order of rs1800625, rs1800624 and rs2070600) of RAGE gene was overrepresented in patients, and conferred a 2.1-fold increased risk of lung cancer (95% confidence interval: 1.52-2.91), independent of confounding factors. Further application of MDR method to five examined polymorphisms identified the overall best interaction model including rs2070600 and rs1130409 polymorphisms. This model had a maximal testing accuracy of 64.63% and a maximal cross-validation consistency of 9 out of 10 at the significant level of 0.006.

Conclusions: Our findings demonstrated a potential interactive contribution of RAGE and APE1 genes to the pathogenesis of lung cancer among Han Chinese. Further studies are warranted to confirm or refute these findings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asians / genetics*
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Receptor for Advanced Glycation End Products / genetics*


  • Receptor for Advanced Glycation End Products
  • APEX1 protein, human
  • DNA-(Apurinic or Apyrimidinic Site) Lyase

Grant support

This work was supported by the National Natural Science Foundation of China (31171353, 31271500), the Ministry of Science and Technology of China (973 Program: 2011CB504201), the Project of Department of Education of Heilongjiang Province (12531780), and the Opening Project of Key Laboratory of Anti-tumor Nature Products R&D, College of Heilongjiang Province. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.