Association of human aryl hydrocarbon receptor gene polymorphisms with risk of lung cancer among cigarette smokers in a Chinese population.
BACKGROUND AND OBJECTIVE: Most of the carcinogenic effects of polycyclic aromatic hydrocarbons present in tobacco smoke are mediated by the aryl hydrocarbon receptor (AHR), a ligand-dependent transcription factor that regulates tobacco-induced expression of carcinogen metabolic enzymes. We hypothesized that genetic variations in AHR might confer individual susceptibility to lung cancer. METHODS: Eight selected single-nucleotide polymorphisms in AHR were genotyped using the Illumina SNP genotyping BeadLab platform in a case-control study of 500 lung cancer patients and 517 cancer-free controls in a Chinese population. RESULTS: We found that significantly increased lung cancer risk was associated with heterozygous genotypes of rs2158041 (adjusted odds ratio=1.53 and 95% confidence interval=1.17-1.99 for GA, compared with the GG genotype) and rs7811989 (adjusted odds ratio=1.48 and 95% confidence interval=1.13-1.93 for GA, compared with the GG genotype), although these two single-nucleotide polymorphisms were in linkage disequilibrium. Furthermore, haplotype analysis revealed significant differences in haplotype distributions of AHR between cases and controls (Global P=1.38e-5). We also observed statistically significant interaction between the polymorphism rs2066853 (p.Arg554Lys) and cumulative cigarette smoking as a discrete or continuous variable (P=0.033 and 0.019, respectively), and the Lys/Lys genotype conferred an increased risk of lung cancer in the heavy smokers (adjusted odds ratio=3.36 and 95% confidence interval=1.07-10.55). CONCLUSION: These findings suggest that AHR polymorphisms and potential gene-smoking interaction may be involved in the etiology of lung cancer. Further large prospective studies with ethnically diverse populations and functional studies are warranted to validate these findings.
Chen, D; Tian, T; Wang, H; Liu, H; Hu, Z; Wang, Y; Liu, Y; Ma, H; Fan, W; Miao, R; Sun, W; Qian, J; Jin, L; Wei, Q; Shen, H; Huang, W; Lu, D
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