Imani Partow, Grigoryan Hasmik, Dudoit Sandrine, Shu Xiao-Ou, Wong Jason, Zhang Luoping, Zhang Junfeng, Hu Wei, Cai Qiuyin, Gao Yutang, Blechter Batel, Rahman Mohammad, Zheng Wei, Rothman Nathaniel, Lan Qing, Rappaport Stephen M
School of Public Health, University of California, Berkeley, Berkeley, CA 94720, USA.
Department of Statistics, University of California, Berkeley, Berkeley, CA 94720, USA.
Antioxidants (Basel). 2025 Mar 13;14(3):335. doi: 10.3390/antiox14030335.
Nearly one fourth of lung cancers occur among never-smokers and are predominately lung adenocarcinomas (LUADs) that are distinct from smoking-related cancers. Causal links between LUADs in never-smokers have been attributed to reactive oxygen species (ROS) arising from airborne fine particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs). These effects are pronounced among East Asian women who experience massive exposures to PM and PAHs and have the highest incidence of LUADs in the world. We employed untargeted adductomics to establish ROS adduct signatures in human serum albumin (HSA) from lung cancer cases and controls from never-smokers in the Shanghai Women's Health Study. Forty-seven HSA adducts were quantified by mass spectrometry, nine of which were selected for association with lung cancer, including Cys34 sulfoxidation products and disulfides of cysteine and homocysteine and two modifications to Lys525. Associated adducts include constituents of redox biology and one-carbon metabolism (OCM), which are pathways associated with lung cancer. Differences in adduct abundance between cases and controls and correlations of adducts with urinary PAHs and dietary factors provide additional evidence linking air pollutants, OCM, and redox biology with lung cancer in never-smokers.
近四分之一的肺癌发生在从不吸烟的人群中，且主要是肺腺癌（LUADs），这类癌症与吸烟相关的癌症不同。从不吸烟者患LUADs的因果联系归因于空气中细颗粒物（PM）和多环芳烃（PAHs）产生的活性氧（ROS）。这些影响在东亚女性中尤为明显，她们大量接触PM和PAHs，且是世界上LUADs发病率最高的人群。我们采用非靶向加合物组学方法，在上海女性健康研究中从不吸烟的肺癌病例和对照的人血清白蛋白（HSA）中建立ROS加合物特征。通过质谱法对47种HSA加合物进行了定量分析，其中9种被选来研究与肺癌的关联，包括半胱氨酸34位的氧化产物、半胱氨酸和同型半胱氨酸的二硫化物以及赖氨酸525位的两种修饰。相关加合物包括氧化还原生物学和一碳代谢（OCM）的成分，这些都是与肺癌相关的途径。病例与对照之间加合物丰度的差异以及加合物与尿中PAHs和饮食因素的相关性，为空气污染物、OCM和氧化还原生物学与从不吸烟者肺癌之间的联系提供了更多证据。
