Background:Allostatic load (AL) is a biomarker of chronic stress associated with various chronic diseases. No study has evaluated the relationship between AL and lung cancer risk.Methods:To address this gap, we analyzed the association between AL and the development of lung cancer in 344,380 participants from the UK Biobank.Results:During the follow-up period from 2006 to 2020, 2517 participants were diagnosed with incident lung cancer. Participants who developed lung cancer had significantly higher AL compared to cancer-free controls (mean: 3.49 vs. 2.87,p< 0.001). In the multivariate analysis, a marginally significant association was observed between higher AL and increased lung cancer risk (per one AL unit: Hazard Ratio [HR] = 1.02, 95% Confidence Interval [CI]: 0.99, 1.04). In the categorical analysis, individuals with high AL (AL > 2) had a 15% higher risk of lung cancer compared to those with low AL (AL ≤ 2) (HR = 1.15, 95% CI: 1.05, 1.25). Stratified analyses revealed that this increased risk was only observed in former (HR = 1.38, 95% CI: 1.06, 1.43) and current smokers (HR = 1.25, 95% CI: 1.10, 1.42) but not in never-smokers (HR = 0.93, 95% CI: 0.74, 1.17). Moreover, we found that demographics, socioeconomics, and other health behaviors could modify the risk association. Finally, among cigarette smoking-related variables, a significant trend of increasing AL was observed with higher pack-years, longer smoking duration, earlier age of smoking initiation, and later age of smoking cessation.Conclusions:These findings suggest that higher AL is associated with an increased risk of lung cancer. The results need to be further confirmed in additional studies.
背景：稳态负荷（AL）是一种与多种慢性疾病相关的慢性应激生物标志物。目前尚无研究评估AL与肺癌风险之间的关系。 方法：为填补这一研究空白，我们基于英国生物银行344,380名参与者的数据，分析了AL与肺癌发病之间的关联。 结果：在2006年至2020年的随访期间，共有2517名参与者被确诊为新发肺癌。与未患癌的对照组相比，肺癌患者的AL水平显著更高（均值：3.49 vs. 2.87，p < 0.001）。多变量分析显示，较高的AL与肺癌风险增加存在临界显著关联（每增加1个AL单位：风险比[HR] = 1.02，95%置信区间[CI]：0.99, 1.04）。在分类分析中，高AL（AL > 2）个体的肺癌风险较低AL（AL ≤ 2）个体高出15%（HR = 1.15，95% CI：1.05, 1.25）。分层分析表明，这种风险增加仅见于既往吸烟者（HR = 1.38，95% CI：1.06, 1.43）和当前吸烟者（HR = 1.25，95% CI：1.10, 1.42），而在从不吸烟者中未观察到显著关联（HR = 0.93，95% CI：0.74, 1.17）。此外，研究发现人口统计学特征、社会经济因素及其他健康行为可能调节该风险关联。最后，在吸烟相关变量中，AL水平随吸烟包年数增加、吸烟持续时间延长、开始吸烟年龄提前及戒烟年龄推迟呈现显著上升趋势。 结论：本研究提示较高的AL与肺癌风险增加相关，该结果仍需通过进一步研究加以验证。
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