Current Biology
Volume 25, Issue 14, 20 July 2015, Pages 1932-1937
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Chronically Alternating Light Cycles Increase Breast Cancer Risk in Mice

https://doi.org/10.1016/j.cub.2015.06.012Get rights and content
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Highlights

  • Chronic CRD leads to decreased tumor suppression and increased body weight gain

  • Disturbed body temperature and corticosterone rhythms precede health effects

  • Sleep disturbance is clearly involved in CRD-induced breast cancer

Summary

Although epidemiological studies in shift workers and flight attendants have associated chronic circadian rhythm disturbance (CRD) with increased breast cancer risk, causal evidence for this association is lacking [1, 2]. Several scenarios have been proposed to contribute to the shift work-cancer connection: (1) internal desynchronization, (2) light at night (resulting in melatonin suppression), (3) sleep disruption, (4) lifestyle disturbances, and (5) decreased vitamin D levels due to lack of sunlight [3]. The confounders inherent in human field studies are less problematic in animal studies, which are therefore a good approach to assess the causal relation between circadian disturbance and cancer. However, the experimental conditions of many of these animal studies were far from the reality of human shift workers. For example, some involved xenografts (addressing tumor growth rather than cancer initiation and/or progression) [4, 5], chemically induced tumor models [6, 7], or continuous bright light exposure, which can lead to suppression of circadian rhythmicity [8, 9]. Here, we have exposed breast cancer-prone p53R270H©/+ WAPCre conditional mutant mice (in a FVB genetic background) to chronic CRD by subjecting them to a weekly alternating light-dark (LD) cycle throughout their life. Animals exposed to the weekly LD inversions showed a decrease in tumor suppression. In addition, these animals showed an increase in body weight. Importantly, this study provides the first experimental proof that CRD increases breast cancer development. Finally, our data suggest internal desynchronization and sleep disturbance as mechanisms linking shift work with cancer development and obesity.

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