Contributory Role of Five Common Polymorphisms of RAGE and APE1 Genes in Lung Cancer among Han Chinese

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 (P(genotype)<0.0005; P(allele)<0.0005), rs2070600 (P(genotype) = 0.005; P(allele) = 0.004) and rs1130409 (P(genotype) = 0.009; P(allele) = 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.