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

Abstract

BackgroundHuman 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. ObjectiveTo investigate the influences of PAH-metal co-exposure, four polymorphisms, and their interactions on oxidative damage levels. MethodsWe 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-F2α and 8-hydroxydeoxyguanosine. We also genotyped four polymorphisms. ResultsIn multiple-pollutant models, 8-iso-prostaglandin-F2α and 8-hydroxydeoxyguanosine were associated with multiple PAH exposure biomarkers, as well as with multiple metals (ptrend < 0.05). Metabolites of phenanthrene and pyrene interacted synergistically with lead and zinc to influence 8-iso-prostaglandin-F2α (βinteraction > 7.75%, false discovery rate-adjusted pinteraction ≤ 2.25 × 10−5). 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-F2α and 8-hydroxydeoxyguanosine were significant (βstd > 0, ptrend < 0.05) and more pronounced in workers with lower metals [p for modifying effect (pME) < 0.040]. Positive associations of some PAHs and metals with 8-iso-prostaglandin-F2α and 8-hydroxydeoxyguanosine were weaker in carriers of rs11614913 CC genotype or C allele (pME < 0.05). ConclusionPAH-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.