Aryl hydrocarbon receptor gene polymorphisms affect lung cancer risk

To evaluate the role of genetic polymorphisms of AhR related to the carcinogen metabolism and cell proliferation, genotypes of three AhR polymorphisms Ex1+185A>G, IVS7+33T>G and Ex10+501G>A were determined in 616 lung cancer cases and 616 lung cancer-free controls. When the effect of each AhR allele on lung cancer risk was evaluated, any AhR genotype did not show the association with lung cancer risk. However, when haplotypes were composed of three AhR SNP sites, non-smokers with GGG haplotype (adjusted OR=1.7, 95% CI, 1.06-2.71) and smokers without GGG haplotype (adjusted OR=2.5, 95% CI, 1.64-3.74) showed significantly increased risk of lung cancer compared to non-smokers without GGG haplotype. Moreover, smokers with GGG haplotype showed the highest risk (adjusted OR=3.2, 95% CI, 2.10-4.74). Particularly, the synergistic effect between AhR haplotype and smoking was more apparent in squamous cell carcinoma (adjusted OR=6.1, 95% CI, 2.53-14.68). This result suggests that haplotypes of AhR gene play an important role in the development of lung cancer and there is a synergistic interaction between AhR gene and smoking for lung cancer risk.