Associations between Opium Route of Use and Exposure to Polycyclic Aromatic Hydrocarbons as Potential Carcinogenicity Mechanism

Background: Opium consumption is carcinogenic, but the impact of the route of use (smoking vs. ingestion) on exposure to potential proposed carcinogens is understudied. Methods: As a nested study within the Golestan Cohort Study, we gathered comprehensive histories of teriak (raw opium), shireh (refined opium sap), and tobacco use by validated questionnaires and selected 100 long-term opium users (50 exclusively ingesting and 50 exclusively smoking), 15 cigarette smokers, and a reference sample using neither. We analyzed spot urine samples for seven hydroxy polycyclic aromatic hydrocarbons (PAH) and cotinine. PAH biomarker concentrations were creatinine-corrected to account for urinary dilution and adjusted for demographic factors and opium use patterns using multivariable linear regression models to evaluate associations between the route of opium use and PAH biomarker concentrations. Results: After excluding opium users who reported no tobacco use but had discordant cotinine concentrations, PAH biomarker concentrations were significantly higher in opium users than the reference sample. Smoking opium was associated with substantially elevated PAH biomarker concentrations compared with ingestion, particularly for Σ2;3-Hydroxyphenanthrene (five-fold increase) and 3-Hydroxyfluorene (4.5-fold increase). For Σ2;3-Hydroxyphenanthrene, concentrations exceeded those of cigarette smokers. No difference was observed between teriak and shireh use. Only among opium smokers, PAH biomarker concentrations decreased by time since last use but remained consistently higher than the reference sample. Conclusions: Opium consumption, regardless of type and route, exposes individuals to PAHs, with greater concentrations of select PAH biomarkers observed for smoking compared with ingestion. Impact: Considering the route of opium use in exposure and cancer risk assessments is crucial.