WCLC 2025 - Posters & ePosters-P3.01.03 Night Shift Work and Lung Cancer Risk: A Prospective Cohort Study With Mediator Analysis From the Uk Biobank

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This prospective cohort study from the UK Biobank investigated the relationship between night-shift work and lung cancer risk among 278,650 employed adults initially free of cancer. Night-shift exposure was classified into categories: day work, rare night shifts, some nights, and permanent night shifts. Incident lung cancer cases (ICD-10: C34) were identified via national registries. The study also analyzed genetic predisposition using a 44-SNP polygenic risk score (PRS), and explored potential mediators including plasma proteins, inflammatory markers, and lifestyle factors.<br /><br />Key findings from Cox regression analysis demonstrated a dose-response association: higher frequency of night-shift work corresponded to an 18-28% increased risk of lung cancer after adjusting for confounders (HR 1.18–1.28, p-trend=0.004). Mediation analysis revealed that smoking accounted for 32.2% of this elevated risk, highlighting it as the dominant behavioral mediator. Additionally, three plasma proteins—prostasin (PRSS8), alkaline phosphatase (ALPP), and carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5)—emerged as novel proteomic mediators linking circadian disruption from night work to tumor microenvironment changes.<br /><br />Subgroup analyses showed significant interaction between night-shift work and smoking status in influencing lung cancer risk, but no interaction with genetic risk. This suggests that the observed association is independent of genetic susceptibility.<br /><br />The study is the first large-scale prospective evidence supporting a dose-response relationship between night-shift work and lung cancer risk, emphasizing the critical role of smoking in mediating this risk. Findings advocate for targeted smoking cessation programs for shift workers to substantially reduce excess lung cancer risk. The identified proteomic mediators provide insight into biological mechanisms and hold potential for biomarker-guided prevention strategies. Clinically, results support optimizing shift schedules and validating these proteomic targets in further longitudinal and experimental research.

Asset Subtitle

Yi Feng

Meta Tag

Speaker Yi Feng

Topic Risk Factors, Risk Reduction & Tobacco Control

Keywords

night-shift work

lung cancer risk

UK Biobank

prospective cohort study

polygenic risk score

smoking mediation

plasma proteins

circadian disruption

proteomic mediators

dose-response relationship