Associations between 25 lung cancer risk-related SNPs and polycyclic aromatic hydrocarbon-induced genetic damage in coke oven workers
Menée en Chine auprès de 1 557 ouvriers travaillant dans une cokerie (fours à coke), cette étude analyse l'association entre 25 polymorphismes à simple nucléotide liés au risque de cancer du poumon et les dommages causés à l'ADN par les hydrocarbures aromatiques polycycliques
Background : Genome-wide association studies have identified multiple SNPs 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 (PAHs). Methods : We cross-sectionally investigated the associations between SNPs from published genome-wide association studies for lung cancer in Asians and PAH-induced genetic damage in 1557 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 enzyme-linked immunosorbent assay, 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 (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 down-regulated 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 while 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. Impact:Lung cancer risk-associated SNPs might influence one's susceptibility to genetic damage caused by PAHs.
http://cebp.aacrjournals.org/content/early/2014/04/01/1055-9965.EPI-13-1251.abstract