Prospective investigation of urinary polycyclic aromatic hydrocarbon metabolites and mortality in the United States: National Health and Nutrition Examination Survey (NHANES) and National Death Index (NDI) Linkage (2001-2015)

Abstract

Background: Polycyclic aromatic hydrocarbons (PAHs) are widely detected chemicals in the U.S. population. Exposure to PAHs has been associated with adverse health outcomes including lung cancer and cardiovascular disease (CVD) though population-based studies examining mortality in relation to PAH exposure is sparse. We aimed to prospectively investigate the relationship of PAH biomarkers and all-cause, cancer-specific, and CVD-specific mortality in a representative sample of the U.S. population. Methods: The study population included 8,168 individuals ≥20 years old who participated in NHANES from 2001-2012. Urinary measures of eight hydroxylated PAH metabolites (OH-PAHs) from four parent compounds (naphthalene, pyrene, phenanthrene, fluorene) were assessed at baseline. Mortality status was ascertained by death certificates through data linkage with the NDI, followed-up until 2015. Survey-weighted Cox proportional hazards regression estimated adjusted hazards ratios (HRadj) and 95% confidence intervals (95%CI). We stratified by active smoking and environmental tobacco smoke (ETS) exposure, sex and race. Results: 912 deaths from all causes were observed over follow-up (mean=8.31 years). A log10 increase in ΣOH-PAHs was associated with a higher all-cause (HRadj: 1.39 [95%CI: 1.21, 1.61]), CVD-specific (HRadj: 1.48 [95%CI: 0.93, 2.34]), and cancer-specific mortality (HRadj: 1.12 [95%CI: 0.76, 1.66]). Stratified models suggest the risk of ΣOH-PAHs and all-cause mortality was higher for active smokers or those exposed to ETS (HRadj: 1.92 [95%CI: 1.39, 2.65]), compared to nonsmokers. In cancer-specific analyses, an increased risk was observed in women (HRadj: 1.49 [95%CI: 1.01, 2.20]), but not men. Compared to other races/ethnicities, risk of CVD-related mortality was highest for non-Hispanic black participants (HRadj: 1.97 [95%CI: 0.79, 4.91]). Discussion: Urinary ΣOH-PAHs was associated with higher all-cause, cancer-specific, and CVD-specific mortality among a representative sample of U.S. adults. This prospective examination of PAH biomarkers, representing exposure across multiple sources, suggests a role for PAHs in both overall mortality and diseases with the highest mortality rates.