Co-exposure to polycyclic aromatic hydrocarbons and metals, four common polymorphisms in microRNA genes, and their gene-environment interactions: Influences on oxidative damage levels in Chinese coke oven workers

Background: Human are often simultaneously exposed to polycyclic aromatic hydrocarbons (PAHs) and metals, yet relatively little is known regarding their co-exposure effects on oxidative damage. Genetic factors and the gene-environment interactions can also determine the severity of oxidative damage. Four polymorphisms in microRNA (miRNA) genes (rs11614913, rs2292832, rs2910164, and rs3746444) have been well-studied to be associated with oxidative damage-related diseases. Objective: To investigate the influences of PAH-metal co-exposure, four polymorphisms, and their interactions on oxidative damage levels. Methods: We conducted a cross-sectional study in 1385 coke oven workers. We quantified exposure levels of PAHs and metals by urinary monohydroxy-PAHs, plasma benzo[a]pyrene-7,8-diol-9,10-epoxide-albumin adducts, and urinary metals, respectively, and measured oxidative damage levels by 8-iso-prostaglandin-F2a and 8hydroxydeoxyguanosine. We also genotyped four polymorphisms. Results: In multiple-pollutant models, 8-iso-prostaglandin-F2 alpha and 8-hydroxydeoxyguanosine were associated with multiple PAH exposure biomarkers, as well as with multiple metals (p(trend) < 0.05). Metabolites of phenanthrene and pyrene interacted synergistically with lead and zinc to influence 8-iso-prostaglandin-F2 alpha (beta(interaction) > 7.75%, false discovery rate-adjusted p(interaction) <= 2.25x10(-5)). Significantly higher 8-hydroxydeoxyguanosine was observed in carriers of rs11614913 CC variant homozygote than TC carriers (p= 0.037). Associations of the number of rs11614913 C allele with increased 8-iso-prostaglandin-F2 alpha and 8-hydroxydeoxyguanosine were significant (beta(std) > 0, p(trend) < 0.05) and more pronounced in workers with lower metals [p for modifying effect (p(ME))< 0.040]. Positive associations of some PAHs and metals with 8-iso-prostaglandin-F2 alpha and 8-hydroxydeoxyguanosine were weaker in carriers of rs11614913 CC genotype or C allele (p(ME) < 0.05). Conclusion: PAH-metal co-exposure, rs11614913, and their interactions may affect oxidative damage levels in Chinese population in a complex manner that are worthy of further investigation.