Light at Night, Night Shift Work, and Cancer: Illustrating Cumulative Exposure to Circadian Disruption through a Thought Experiment.

Light at night (LAN) and night shift work (NSW) have been hypothesized to be carcinogenic through circadian disruption. However, cancer epidemiology examining these hypotheses in environmental or occupational settings has yielded inconclusive results. The thought experiment "The city that never sleeps" illustrates why it is reductionist to focus solely on LAN or on NSW: a link between both plausible cancer pathways could be chronodisruption (CD). CD is operationalized as the misalignment between external time (due to exposures in both the environment and the workplace) and the body's internal time; CD causes circadian disruption, conceptualized as disrupted circadian organization. CD occurs whenever individuals are awake during their biological night, which is associated with chronotype, and this can be quantified. This perspective illustrates a conceptual framework for cumulative CD doses to investigate cancer risks associated with circadian disruption and outlines six practical steps for designing studies to evaluate this concept, including a potential role of biomarkers.