Biomarkers of opioids, volatile organic compounds, and polycyclic aromatic hydrocarbons and lung cancer incidence among opium users

BACKGROUND: Opium consumption, a recognized carcinogen, is associated with lung cancer. However, the relative contributions of its potentially carcinogenic constituents to lung cancer risk remain unclear. METHODS: We conducted a nested case-control study among the opium users in the Golestan Cohort Study, including 53 incident lung cancer cases and 53 controls matched on age, sex, tobacco use, place of residence, and enrollment time. Urinary biomarkers of opioids, volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs), cotinine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and creatinine were measured in baseline samples. Adjusted logistic regression analyses, as well as mediation analyses, were used to evaluate the associations between biomarker concentrations and lung cancer incidence. RESULTS: We found statistically significant associations between 3- and 6- glucuronides of morphine, as well as metabolites of acrylonitrile/ethylene oxide (2-hydroxyethyl mercapturic acid) and propylene oxide (2-hydroxypropyl mercapturic acid), and lung cancer among opium users, especially those who smoked opium. Associations between VOC metabolites and lung cancer were independent of opioid biomarkers, and mediation analysis showed no evidence that VOCs mediate the effects of opioid biomarkers on lung cancer. No associations were observed for PAH biomarkers, cotinine and NNAL. CONCLUSIONS: Our findings provide biochemical evidence supporting the association between opium use and lung cancer, highlighting independent mechanisms related to both opioid and non-opioid components of opium, with varying effects by route of use. IMPACT: Opioids and chemical constituents produced during opium consumption must be considered in cancer risk assessment.