Effect of polycyclic aromatic hydrocarbons on cancer risk causally mediated via vitamin D levels

Polycyclic aromatic hydrocarbons (PAHs) widely exist in environmental substrates and are closely related to individual circulating vitamin D levels and tumorigenesis. Therefore, we proposed to evaluate the relationship between PAH exposure, vitamin D, and the risks for 14 cancer types via a causal inference framework underlying the mediation analysis. We evaluated seven urine monohydroxylated PAH (OH-PAH) and serum vitamin D concentrations of 3306 participants from the National Health and Nutrition Examination Survey between the 2013 and 2016 survey cycles and measured PAH concentrations in 150 subjects from the Nanjing cohort. We observed a significant negative dose-response relationship between increased OH-PAH levels and vitamin D deficiency. Each unit increase in ∑OH-PAHs could lead to a decrease in vitamin D levels (βadj  = -0.98, Padj  = 2.05 × 10-4 ). Body mass index could have interaction effects with ∑OH-PAHs and affect vitamin D levels. Coexposure to naphthalene and fluorene metabolites mutually affected vitamin D levels. Notably, vitamin D could causally mediate the relationship between OH-PAHs and nine types of cancer (e.g., colorectal cancer, liver cancers, etc.). This study first emphasizes the causal cascade of individual OH-PAHs, vitamin D, and cancer risk, providing insights into prevention via the environment.