Association of aryl hydrocarbon receptor gene polymorphisms and urinary 1-hydroxypyrene in polycyclic aromatic hydrocarbon-exposed workers.
Polycyclic aromatic hydrocarbons (PAH) in coke oven emissions could cause lung cancer in human. Individual's genotype of the metabolic enzymes and early biological changes were known to be associated with the susceptibility of cancer development. Knowledge of metabolic gene polymorphisms, which affect on the urinary 1-hydroxypyrene (1-OHP), could benefit us in understanding the interindividual difference in the mechanism of PAH-induced carcinogenesis. In this study, we investigated the association of aryl hydrocarbon receptor (AhR) gene polymorphisms and urinary 1-OHP. One hundred forty-seven workers exposed to PAH and 69 nonexposure workers were recruited. Seven tagging single nucleotide polymorphisms in AhR gene were selected by pariwise r(2) method and minor allele frequency cutoff of 0.05 from Chinese genotype data in HapMap project. These seven tagging single nucleotide polymorphisms were genotyped by PCR-based methods. Multivariate analysis of covariance revealed that the levels of 1-OHP in PAH-exposed workers carrying genotype CT were lower than workers carrying wild genotype TT at loci rs10250822 and rs2282885 of AhR gene (P = 0.032 and 0.044, respectively). In PAH-exposed workers, the urinary 1-OHP levels showed a linear correlation (P(trend) = 0.041) with the genotypes at locus rs2282885, especially in low and moderate exposure groups. In contrast, no significant association was found between urinary 1-OHP level and AhR genotypes among nonexposed workers. Our findings indicated that polymorphisms of AhR gene were associated with the level of 1-OHP among PAH-exposed workers, suggesting that AhR-mediated signaling might contribute to individual susceptibility to PAH exposure.
Bin
Ping
P
National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, PR China.
Leng
Shuguang
S
Cheng
Juan
J
Dai
Yufei
Y
Huang
Chuanfeng
C
Pan
Zufei
Z
Niu
Yong
Y
Duan
Huawei
H
Li
Haishan
H
Liu
Qingjun
Q
Chen
Wen
W
Zheng
Yuxin
Y
D002681:China / Q000453:epidemiology; D004247:DNA / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics; D009784:Occupational Diseases / Q000139:chemically induced / Q000235:genetics / Q000652:urine*; D016273:Occupational Exposure / Q000009:adverse effects*; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011721:Pyrenes / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*
D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; D018336:Receptors, Aryl Hydrocarbon; D004247:DNA; C033146:1-hydroxypyrene