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


CONCLUSIONS
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
Dan
D
State Key Laboratory of Genetic Engineering and Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
Tian
Tian
T
Wang
Haifeng
H
Liu
Hongliang
H
Hu
Zhibin
Z
Wang
Yi
Y
Liu
Yanhong
Y
Ma
Hongxia
H
Fan
Weiwei
W
Miao
Ruifen
R
Sun
Weiwei
W
Wang
Yi
Y
Qian
Ji
J
Jin
Li
L
Wei
Qingyi
Q
Shen
Hongbing
H
Huang
Wei
W
Lu
Daru
D
D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D005260:Female; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008175:Lung Neoplasms / Q000209:etiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics*
D018336:Receptors, Aryl Hydrocarbon