Abstract
Genome-wide association studies (GWAS) have identified multiple single-nucleotide polymorphisms (SNP) associated with lung cancer. However, whether these SNPs are associated with genetic damage, a crucial event in cancer initiation and evolution, is still unknown. We aimed to establish associations between these SNPs and genetic damage caused by the ubiquitous carcinogens, polycyclic aromatic hydrocarbons (PAH). We cross-sectionally investigated the associations between SNPs from published GWAS for lung cancer in Asians and PAH-induced genetic damage in 1,557 coke oven workers in China. Urinary PAH metabolites, plasma benzo[a]pyrene-r-7,t-8,c-10-tetrahydrotetrol-albumin (BPDE-Alb) adducts, urinary 8-hydroxydeoxyguanosine (8-OHdG), and micronuclei (MN) frequency were determined by gas chromatography-mass spectrometry, sandwich ELISA, high-performance liquid chromatography, and cytokinesis-block micronucleus assay, respectively. 13q12.12-rs753955C was suggestively associated with elevated 8-OHdG levels (P = 0.003). Higher 8-OHdG levels were observed in individuals with rare allele homozygotes (CC) than in TT homozygotes (β, 0.297; 95% confidence interval, 0.124-0.471; P = 0.001). 9p21-rs1333040C, 10p14-rs1663689G, and 15q25.1-rs3813572G were significantly associated with lower MN frequency (P values were 0.002, 0.001, and 0.005, respectively). 10p14-rs1663689G polymorphism downregulated the relationship of the total concentration of PAH metabolites to 8-OHdG levels (Pinteraction = 0.002). TERT-rs2736100G and VTI1A-rs7086803A aggravated the relationship of BPDE-Alb adducts to MN frequency, whereas BPTF-rs7216064G attenuated that correlation (all Pinteraction < 0.001). Lung cancer risk-associated SNPs and their correlations with PAH exposure were associated with 8-OHdG levels and MN frequency. Lung cancer risk-associated SNPs might influence one's susceptibility to genetic damage caused by PAHs. Cancer Epidemiol Biomarkers Prev; 23(6); 986-96. ©2014 AACR.
Highlights
Lung cancer is the leading cause of cancer-related mortality worldwide, including China [1, 2], and is a complex disease caused both by genetic and environmen-Authors' Affiliations: 1Key Laboratory of Environment and Health and State Key Laboratory of Environmental Health for Incubation, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology; and 2Institute of Industrial Health, Wuhan Iron and Steel Corporation, Wuhan, Hubei, ChinaNote: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers and Prevention Online.Ó2014 American Association for Cancer Research.tal factors and by their interactions [3, 4]
Genome-wide association studies (GWAS) have identified multiple single-nucleotide polymorphisms (SNP) that are associated with lung cancer risks, supporting the suggestion that inherited genetic factors play a significant role in lung cancer development
We explored the relationships between these SNPs and polycyclic aromatic hydrocarbons (PAH) exposure, which were assessed by PAH metabolites and plasma benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrolalbumin (BPDE-Alb) adducts
Summary
Lung cancer is the leading cause of cancer-related mortality worldwide, including China [1, 2], and is a complex disease caused both by genetic and environmen-Authors' Affiliations: 1Key Laboratory of Environment and Health and State Key Laboratory of Environmental Health for Incubation, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology; and 2Institute of Industrial Health, Wuhan Iron and Steel (group) Corporation, Wuhan, Hubei, ChinaNote: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers and Prevention Online (http://cebp.aacrjournals.org/).Ó2014 American Association for Cancer Research.tal factors and by their interactions [3, 4]. Genome-wide association studies (GWAS) have identified multiple single-nucleotide polymorphisms (SNP) that are associated with lung cancer risks, supporting the suggestion that inherited genetic factors play a significant role in lung cancer development. Environmental pollutants such as polycyclic aromatic hydrocarbons (PAH) contribute to lung cancer risks [5,6,7]. Genome-wide association studies (GWAS) have identified multiple single-nucleotide polymorphisms (SNP) associated with lung cancer. Whether these SNPs are associated with genetic damage, a crucial event in cancer initiation and evolution, is still unknown. We aimed to establish associations between these SNPs and genetic damage caused by the ubiquitous carcinogens, polycyclic aromatic hydrocarbons (PAH)
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