Opium Consumption and Lung Cancer: From Self-reported Use to Exposure Biomarkers

Opium consumption is most prevalent in Southwestern and South Asia, particularly in regions surrounding the major opium-producing areas of the Golden Crescent. The International Agency for Research on Cancer classifies opium consumption as a group 1 human carcinogen, with sufficient evidence for lung, laryngeal, and urinary bladder cancers. Opium consumption involves complex exposure profiles, including combustion-derived exposures from opium and its fuels, as well as coexposures from tobacco smoking and indoor biomass burning. Recent molecular epidemiologic research in the prospective Golestan Cohort Study provides an opportunity to move beyond self-reported opium use by characterizing internal exposure to multiple opioid and non-opioid constituents. In a nested case-control study of 53 matched lung cancer pairs among opium users, 35 urinary metabolites reflecting exposure to opiates, volatile organic compounds, polycyclic aromatic hydrocarbons, and nicotine were measured. Higher concentrations of morphine-3-glucuronide, morphine-6-glucuronide, 2-hydroxypropyl mercapturic acid, and 2-hydroxyethyl mercapturic acid were associated with lung cancer. These findings provide an important initial demonstration of the potential of urinary biomarkers to characterize complex exposures associated with opium consumption. Future studies integrating driver mutations, mutational signatures, and tumor microenvironment characteristics may provide further insight into mechanisms of opium-related lung carcinogenesis and inform cancer prevention and precision oncology. See related article by Naghash et al., p. 1880.