UCLA

BACKGROUND: In recent years, the association between depression and various chronic diseases has attracted widespread attention. However, the effect of depression on lung cancer incidence has not been well studied. This study aimed to explore whether depression increases the incidence of lung cancer and to analyze the mediating and moderating roles of smoking in this relationship. METHODS: This study used large-scale longitudinal data sourced from the Womens Health Initiative, encompassing 123,961 postmenopausal women. Depressive symptoms were measured using the 8-item Burnam regression algorithm with a cut-point of 0.06, and depression was defined as either depressive symptoms or antidepressant use at baseline. The relationship between depression and lung cancer incidence was examined using a multivariate Cox proportional hazards regression model. A four-way decomposition causal mediation approach was employed to investigate the potential mediating and moderating effects of smoking. RESULTS: After a mean follow-up of 17.6 years, 3434 cases of lung cancer were identified. The incidence rate of lung cancer was higher among individuals with depression compared to those without (HR: 1.15, 95% CI: 1.05-1.26). Cigarette smoking partially mediated the relationship between depression and lung cancer incidence, explaining about 27% of the association effect. CONCLUSIONS: This study identified a significant association between depression and lung cancer incidence, and smoking partially mediates this relationship. This highlights that managing depression may play a key role in reducing lung cancer risk and decreasing tobacco use. Psychological support should be integrated with traditional smoking cessation programs for lung cancer prevention.