Background:Lung adenocarcinoma in non-smoking women represents a distinct clinical entity that cannot be fully explained by traditional exposure-centered carcinogenic models. Although ambient air pollution is a recognized risk factor, sex-specific vulnerability suggests the involvement of additional biological modulators shaping inflammatory, immune, and proliferative responses.Main body:In this conceptual review, we integrate epidemiological, experimental, and mechanistic evidence to propose a multisystem framework of lung carcinogenesis in non-smoking women. We delineate a central carcinogenic spine encompassing lung epithelial injury, chronic inflammation, growth factor signaling activation—particularly epidermal growth factor receptor (EGFR) pathways—and tumor microenvironment remodeling. Within this framework, three interacting domains function as biological modulators that amplify carcinogenic processes: chemosensory–neural–immune modulation, hormonal–endocrine signaling including estrogen–EGFR crosstalk, and psychosocial stress–hypothalamic–pituitary–adrenal (HPA) axis dysregulation. These domains converge through feedback mechanisms that reinforce systemic dysregulation and tumor-promoting microenvironments.Implications:This integrative model provides a biologically grounded perspective on female-specific vulnerability to lung adenocarcinoma and informs precision prevention, risk stratification, and ESG-informed public health strategies beyond conventional exposure reduction.
背景：非吸烟女性肺腺癌是一种独特的临床类型，其发生机制无法完全用传统的以暴露为中心的致癌模型解释。尽管环境空气污染是明确的危险因素，但性别特异性易感性提示存在其他生物调节因子参与调控炎症、免疫及增殖反应。
主体：在本概念性综述中，我们整合流行病学、实验及机制研究证据，提出非吸烟女性肺癌发生的多系统框架。我们描绘了一个以肺上皮损伤、慢性炎症、生长因子信号激活（特别是表皮生长因子受体通路）及肿瘤微环境重塑为核心的致癌核心轴。在此框架内，三个相互作用的领域作为生物调节因子放大致癌进程：化学感受-神经-免疫调节、包含雌激素-表皮生长因子受体交互作用的激素-内分泌信号传导，以及心理社会压力-下丘脑-垂体-肾上腺轴失调。这些领域通过反馈机制相互交汇，强化全身性失调和促肿瘤微环境。
意义：这一整合模型为女性肺腺癌特异性易感性提供了生物学基础视角，并为精准预防、风险分层以及超越传统暴露减少的ESG导向公共卫生策略提供了理论依据。
肿瘤(癌症)患者之家