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Background  Lung cancer is the most common cause of cancer-related deaths worldwide. The aim of this study was to investigate the association of five extensively-studied polymorphisms in  PTGS2  (rs689466, rs5275, rs20417) and  CYP2E1  (rs2031920, rs6413432) genes with lung cancer risk in a large northeastern Chinese population.    Methodology/Principal Findings  This is a hospital-based case-control study involving 684 patients with lung cancer and 604 cancer-free controls. Genotyping was performed using the PCR-LDR method. Data were analyzed using Haplo.stats and MDR programs. There were significant differences between patients and controls in allele/genotype distributions of rs5275 ( P  = 0.002/0.003) and rs6413432 ( P  = 0.037/0.044), as well as in genotype distributions of rs689466 ( P  = 0.02). The risk for lung cancer associated with the rs5275-C mutant allele was decreased by 60% (95% CI [confidence interval]: 0.21–0.74;  P  = 0.004) under the recessive model. Carriers of rs689466-G mutant allele had a 28% (95% CI: 0.57–0.92;  P  = 0.008) reduced risk of developing lung cancer relative to the AA genotype carriers. In haplotype analysis, haplotype G-C-C-T (in order of rs689466, rs5275, rs2031920 and rs6413432) decreased the odds of lung cancer by 28% (95% CI: 0.51–0.93;  P  = 0.019) after adjusting for confounding factors, whereas haplotype A-T-T-T had 1.49-fold (95% CI: 1.21–1.79;  P  = 0.012) increased risk for lung cancer. Using MDR method, the overall best model including rs5275, rs689466 and rs6413432 polymorphisms was identified with a maximal testing accuracy of 66.1% and a maximal cross-validation consistency of 10 out of 10 ( P  = 0.003).    Conclusions/Significance  Our findings demonstrated a potentially synergistic association of  PTGS2  and  CYP2E1  polymorphisms with the underlying cause of lung cancer in northeastern Chinese.

Synergistic Association of PTGS2 and CYP2E1 Genetic Polymorphisms with Lung Cancer Risk in Northeastern Chinese