阿片消费与肺癌：从自我报告使用到暴露生物标志物

文献信息

中文摘要

阿片消费在西南亚和南亚最为普遍，尤其是在金新月主要阿片产区周边地区。国际癌症研究机构将阿片消费列为1类人类致癌物，已有充分证据支持其与肺癌、喉癌和膀胱癌的关联。阿片消费涉及复杂的暴露特征，包括阿片及其燃料燃烧产生的暴露，以及烟草吸烟和室内生物质燃烧的共暴露。近期在前瞻性戈勒斯坦队列研究中开展的分子流行病学研究，为超越自我报告的阿片使用、刻画多种阿片类和非阿片类成分的内暴露提供了机会。在一项纳入53对匹配肺癌病例对照的阿片使用者巢式病例对照研究中，测定了反映阿片类、挥发性有机化合物、多环芳烃和尼古丁暴露的35种尿液代谢物。较高浓度的吗啡-3-葡萄糖醛酸苷、吗啡-6-葡萄糖醛酸苷、2-羟丙基硫醇尿酸和2-羟乙基硫醇尿酸与肺癌相关。这些发现初步重要地展示了尿液生物标志物在刻画与阿片消费相关的复杂暴露方面的潜力。未来整合驱动突变、突变特征和肿瘤微环境特征的研究可能进一步揭示阿片相关肺癌发生机制，并为癌症预防和精准肿瘤学提供信息。参见Naghash等人的相关文章，第1880页。

英文摘要

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.