Association of human aryl hydrocarbon receptor gene polymorphisms with risk of lung cancer among cigarette smokers in a Chinese population.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • January 2009

Published In

Volume / Issue

  • 19 / 1

Start / End Page

  • 25 - 34

PubMed ID

  • 18818557

Pubmed Central ID

  • 18818557

International Standard Serial Number (ISSN)

  • 1744-6872

Digital Object Identifier (DOI)

  • 10.1097/FPC.0b013e328316d8d8

Language

  • eng

Conference Location

  • United States