Associations between 25 Lung Cancer Risk-Related SNPs and Polycyclic Aromatic Hydrocarbon-Induced Genetic Damage in Coke Oven Workers

作者：Dai, Xiayun; Deng, Siyun; Wang, Tian; Qiu, Gaokun; Li, Jun; Yang, Binyao; Feng, Wei; He, Xiaosheng; Deng, Qifei; Ye, Jian; Zhang, Wangzhen; He, Meian; Zhang, Xiaomin; Guo, Huan; Wu, Tangchun^*

来源：Cancer Epidemiology Biomarkers & Prevention, 2014, 23(6): 986-996.

DOI：10.1158/1055-9965.EPI-13-1251

• GENOME-WIDE ASSOCIATION
• SUSCEPTIBILITY LOCI
• OXIDATIVE STRESS
• DNA-DAMAGE
• CHINESE POPULATION
• EXPOSURE
• ADENOCARCINOMA
• POLYMORPHISMS
• BIOMARKERS
• MORTALITY

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-OHdGlevels were observed in individuals with rare allele homozygotes (CC) than in TT homozygotes (beta, 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 (P-interaction = 0.002). TERT-rs2736100G and VTI1A-rs7086803A aggravated the relationship of BPDE-Alb adducts to MN frequency, whereas BPTF-rs7216064G attenuated that correlation (all P-interaction < 0.001). @@@ Conclusions: Lung cancer risk-associated SNPs and their correlations with PAH exposure were associated with 8-OHdG levels and MN frequency. @@@ Impact: Lung cancer risk-associated SNPs might influence one's susceptibility to genetic damage caused by PAHs.

• 出版日期2014-6
• 单位华中科技大学