Cigarette Smoking, MDM2 SNP309, Gene-Environment Interactions, and Lung Cancer Risk: A Meta-Analysis

MDM2 SNP309 polymorphism was found to contribute to genetic susceptibility to lung cancer in humans. However, association studies on these polymorphisms in lung cancer cases have shown conflicting results. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratio (OR) with 95% confidence interval (CI) was applied to assess the strength of association between MDM2 SNP309 polymorphism and risk of lung cancer development. The logistic regression indicated that the genetic model was most likely to be recessive. Using a recessive model, the pooled OR estimating the genotype GG against the T-allele carriers (GT + TT) were calculated. Eight studies, including 6063 cases and 6678 controls, were involved in this meta-analysis. Overall meta-analysis indicated that MDM2 SNP309 GG genotypes have an approximate 16% increased risk for lung cancer development with a statistical significance (OR = 1.16; 95% CI: 1.01-1.34). In the subgroup analyses based on ethnicities, no significant elevated risk was associated with MDM2 SNP309 genotypes found in Asian and Europeans. No significant increased risk was associated with MDM2 SNP309 genotypes found in ever smokers. MDM2 SNP309 GG genotype had an approximate 36% enhanced risk of lung cancer development with statistical significance in never smokers (OR = 1.36; 95% CI: 1.10-1.68). Although some bias cannot be excluded, this meta-analysis supports the view that MDM2 SNP309 gene is a low-penetrance susceptible gene in the development of lung cancer, and the relationship of MDM2 SNP309 and lung cancer is stronger for never smokers.