Allostatic Load, Cigarette Smoking, and Lung Cancer Risk

<b>Background:</b> 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. <b>Methods:</b> To address this gap, we analyzed the association between AL and the development of lung cancer in 344,380 participants from the UK Biobank. <b>Results:</b> 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, <i>p</i> < 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. <b>Conclusions:</b> 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.