In a cohort of 278,650 participants, 1,524 cases of lung cancer were identified over a median follow-up of 10.64 years.
There is a significant dose-response relationship between current and lung cancer risk, with higher risks associated with more frequent night shifts.
Specifically, working some night shifts is associated with a of 1.28 for lung cancer compared to those who never or rarely work night shifts.
Smoking is identified as a significant mediator in the association between night shift work and lung cancer risk.
Key biological mediators identified include prostasin, alkaline phosphatase, and carcinoembryonic antigen-related cell adhesion molecule 5, which together explain over 25 percent of the total effect.
Simplified
STUDY OBJECTIVES: This study investigated the association between and lung cancer risk using data from the UK Biobank cohort of 278 650 participants, while exploring potential biological mediators and gene-environment interactions.
METHODS: Cox proportional hazards models assessed relationships between current night shift status, lifetime duration, and frequency of night shifts with lung cancer incidence. Mediation analyses examined physical measurements, lifestyle habits, blood immune cell parameters, and plasma proteins as potential mediating pathways. Polygenic risk scores evaluated genetic predisposition interactions.
RESULTS: During a median follow-up of 10.64 years, 1524 incident lung cancer cases were identified. A significant dose-response relationship was observed between increasing categories of current night shift work and lung cancer risk (Shift but never/rarely night shifts 1.18, 95% CI = 1.00 to 1.39, p = .047; Some night shifts HR 1.28, 95% CI = 1.06 to 1.55, p = .010; Some night shifts HR 1.19, 95% CI = 0.90 to 1.57, p = .220; p for trend = .004). Smoking plays a significant mediating role in this association. Mediation analysis also identified prostasin (PRSS8), alkaline phosphatase (ALPP), and carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as key mediators, collectively explaining over 25 per cent of the total effect.
CONCLUSIONS: This study suggests that night shift work, particularly when combined with smoking, is associated with an increased risk of lung cancer. The identification of potential mediators such as prostasin, ALPP and CEACAM5 provides insights into the underlying biological mechanisms. Future research should validate these findings and explore targeted prevention strategies for high-risk populations.
Key numbers
1.84
Increased Lung Cancer Risk
comparing night shift workers to day workers.
32.28%
Smoking Mediation Proportion
Proportion of the total effect attributed to smoking status.
1524
Incident Lung Cancer Cases
Total lung cancer cases during a median follow-up of 10.64 years.
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Financial disclosure: The authors declare that they have no financial relationships or financial conflicts of interest to disclose. Non-financial disclosure: The authors declare that they have no non-financial conflicts of interest to disclose.
