Night Shift Work Tied to Elevated Lung Cancer Risk, Especially Among Smokers

Night shift work and smoking are associated with an increased risk for lung cancer through direct and indirect pathways, according to a study published in Sleep.

Researchers conducted a prospective cohort study using data from the UK Biobank to investigate the association between night shift work and lung cancer, and to explore potential biological mediators and gene-environment interactions.

Participants who were employed or self-employed and who did not have cancer at baseline were included in the study. Analysis of the potential mediating effects of blood immune cell parameters targeted 10 hematologic inflammation indicators from the Biobank baseline measurements. Proteomic mediation analysis was also performed. Linear regression and Cox regression models were employed for statistical analysis, and 3 models were created:

• Model 1: Adjusted for age and sex
• Model 2: Adjusted for age, sex, race, Townsend deprivation index, education, alcohol frequency, sleep duration, and family history of lung cancer
• Model 3: Includes adjustments from Models 1 and 2, plus adjustments for fruit intake, oily fish intake, and processed meat intake

A total of 278,650 participants were included in the study (mean age, 52.7 years; men, 48.4%; White, 93.7%) and were categorized as day workers (82.1%), shift but never/rarely night shifts (8.8%), some night shifts (6.5%), and usual/permanent night shifts (2.6%).

A total of 1524 incident lung cancer cases were identified during a median follow-up of 10.6 years. Compared with day workers, those who worked night shifts were more likely to be men, have a higher Townsend deprivation index, lower education level, and higher body mass index (BMI). Compared with night shift workers, day workers were less likely to smoke, ate less processed meat, ate more fruits and oily fish, and drank more alcohol.

A dose-response relationship was observed between lung cancer risk and increasing categories of current night shift work. Individuals who engaged in rotating shifts with usual or permanent night shifts had the highest risk for lung cancer in Model 1 (hazard ratio [HR], 1.84; 95% CI, 1.40-2.42; P <.001), and the association remained significant in Model 2 (HR, 1.41; 95% CI, 1.07-1.86; P <.001). A significant positive trend was observed in Model 3 (P =.004).

For average frequency of night shift work, only those who worked fewer than 3-night shifts per month showed a significant impact on lung cancer risk across all models (Model 3; HR, 1.88; 95% CI, 1.08-3.25; P =.025). In Model 1, a significant association was observed for lung cancer risk among those who worked more than 8 shifts per month (HR, 1.46; 95% CI, 1.01-2.11; P =.043), but not for 3 to 8 shifts per month.

Analysis of lifetime duration of night shift work showed no significant impact of different durations of night shifts and lung cancer risk in Model 1 (<10 years: HR, 1.28; 95% CI, 0.81-1.88; P =.0322; ≥10 years: HR, 1.28; 95% CI, 0.88-1.85; P =.197); similar results were observed for Models 2 and 3. Sensitivity analysis was consistent with the main analyses.

No significant interaction was observed between night shift work and genetic factors, but smoking status significantly modified the relationship. No night shift work categories were significantly associated with lung cancer risk, but previous smokers with “shift but never/rarely night shift” work (HR, 1.42; 95% CI, 1.11-1.82; P =.006) or “some night shifts” (HR, 1.45; 95% CI, 1.06-1.98; P =.020) and current smokers working “some night shifts” (HR, 1.31; 95% CI, 1.02-1.70; P =.036) had significantly higher lung cancer risk vs day workers with a similar smoking status.

Mediation analysis showed that the impact of night work on risk for lung cancer primarily relied on direct effects; contribution from immune mediation pathways was limited. A total of 44 plasma proteins had a mediation proportion of more than 10% and 9 proteins had a proportion higher than 20%. Prostasin (PRSS8), alkaline phosphatase (ALP), and carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) exhibited the highest mediation proportions.

Smoking status, BMI, processed meat intake, and fruit intake all showed significant mediating effects.

Study limitations included self-reported shift work, lack of generalizability, and residual confounding.

“Clinically, these results highlight the importance of workplace interventions such as optimized shift schedules and smoking cessation support for high-risk populations,” the researchers concluded.