title: Associations between 25 lung cancer risk-related SNPs and polycyclic aromatic hydrocarbon-induced genetic damage in coke oven workers.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Lung cancer risk-associated SNPs and their correlations with PAH exposure were associated with 8-OHdG levels and MN frequency.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Authors' Affiliations: Key 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 Institute of Industrial Health, Wuhan Iron and Steel (group) Corporation, Wuhan, Hubei, China.
authors.forename: Xiayun
authors.initials: X
authors.lastname: Dai
authors.affiliation: Authors' Affiliations: Key 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 Institute of Industrial Health, Wuhan Iron and Steel (group) Corporation, Wuhan, Hubei, China.
authors.forename: Siyun
authors.initials: S
authors.lastname: Deng
authors.affiliation: Authors' Affiliations: Key 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 Institute of Industrial Health, Wuhan Iron and Steel (group) Corporation, Wuhan, Hubei, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
authors.affiliation: Authors' Affiliations: Key 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 Institute of Industrial Health, Wuhan Iron and Steel (group) Corporation, Wuhan, Hubei, China.
authors.forename: Gaokun
authors.initials: G
authors.lastname: Qiu
authors.affiliation: Authors' Affiliations: Key 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 Institute of Industrial Health, Wuhan Iron and Steel (group) Corporation, Wuhan, Hubei, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Authors' Affiliations: Key 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 Institute of Industrial Health, Wuhan Iron and Steel (group) Corporation, Wuhan, Hubei, China.
authors.forename: Binyao
authors.initials: B
authors.lastname: Yang
authors.affiliation: Authors' Affiliations: Key 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 Institute of Industrial Health, Wuhan Iron and Steel (group) Corporation, Wuhan, Hubei, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.affiliation: Authors' Affiliations: Key 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 Institute of Industrial Health, Wuhan Iron and Steel (group) Corporation, Wuhan, Hubei, China.
authors.forename: Xiaosheng
authors.initials: X
authors.lastname: He
authors.affiliation: Authors' Affiliations: Key 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 Institute of Industrial Health, Wuhan Iron and Steel (group) Corporation, Wuhan, Hubei, China.
authors.forename: Qifei
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Authors' Affiliations: Key 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 Institute of Industrial Health, Wuhan Iron and Steel (group) Corporation, Wuhan, Hubei, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ye
authors.affiliation: Authors' Affiliations: Key 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 Institute of Industrial Health, Wuhan Iron and Steel (group) Corporation, Wuhan, Hubei, China.
authors.forename: Wangzhen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Authors' Affiliations: Key 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 Institute of Industrial Health, Wuhan Iron and Steel (group) Corporation, Wuhan, Hubei, China.
authors.forename: Meian
authors.initials: M
authors.lastname: He
authors.affiliation: Authors' Affiliations: Key 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 Institute of Industrial Health, Wuhan Iron and Steel (group) Corporation, Wuhan, Hubei, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Authors' Affiliations: Key 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 Institute of Industrial Health, Wuhan Iron and Steel (group) Corporation, Wuhan, Hubei, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Guo
authors.affiliation: Authors' Affiliations: Key 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 Institute of Industrial Health, Wuhan Iron and Steel (group) Corporation, Wuhan, Hubei, China wut@mails.tjmu.edu.cn.
authors.forename: Tangchun
authors.initials: T
authors.lastname: Wu
mesh_terms: D000328:Adult; D000395:Air Pollutants, Occupational; D003077:Coke; D003430:Cross-Sectional Studies; D004249:DNA Damage; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D011084:Polycyclic Aromatic Hydrocarbons / Q000652:urine*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D000395:Air Pollutants, Occupational; D003077:Coke; D011084:Polycyclic Aromatic Hydrocarbons