Impact of Adverse Childhood Experience on Lung Cancer Risk: A Population-Based Prospective Cohort Study

Introduction This study investigates the cumulative association between adverse childhood experiences and lung cancer risk and analyzes whether a healthy lifestyle could modify this association. Methods Using the UK Biobank, we analyzed 156,798 participants who completed a baseline Mental Health Questionnaire. Lung cancer risk from age 30 was recorded, classifying childhood adversity severity using cumulative categories (none, mild 1-2 types, and severe ≥3 types). We used multi-variable Cox regression and competing risk models to estimate hazard ratios (HR) between childhood adversity and lung cancer risk. Mediation analyses assessed the role of smoking. Results During a median follow-up of 41 years from age 30, 677 participants were diagnosed with lung cancer, and 401 died. Lung cancer risk increased progressively with increasing childhood adversity severity. Compared with individuals without childhood adversity, those who experienced any adversity had a 37% higher risk of lung cancer (HR 1.37, 95% CI 1.15-1.63), while those with severe adversity had an 82% higher risk (HR 1.82, 95% CI 1.27-2.62), demonstrating a clear summative effect. Participants who experienced any form of adversity had a 18% increased risk of dying from lung cancer (HR 1.18 1.05-1.32). Smoking severity was higher among participants with childhood adversity and accounted for approximately 40% of the observed association. Timely smoking cessation was associated with a substantially lower risk of lung cancer (approximately 75%). However, in the severe adversity group, smoking cessation did not provide a protective effect (HR 0.47 0.20-1.09). Smoking cessation significantly reduced lung cancer mortality regardless of adversity level. Conclusion Childhood adversity was associated with a higher risk of lung cancer in a cumulative manner, even after accounting for non-cancer death. Smoking accounted for a substantial proportion of the association between childhood adversity and lung cancer risk, and smoking cessation was associated with lower lung cancer risk across adversity levels. The association between childhood adversity and lung cancer remained robust, warranting further research to explore additional mediating pathways.