Mutation Research/Genetic Toxicology and Environmental Mutagenesis
ReviewWorking against our endogenous circadian clock: Breast cancer and electric lighting in the modern world
Section snippets
Circadian rhythms
The circadian rhythm is an endogenous oscillation of approximately 24 h in physiology and metabolism with characteristic cycles of, among many other attributes, body temperature, hormone secretion, sleep/wake cycle, alertness, and gene expression [1]. ‘Endogenous’ means that the rhythm persists indefinitely in a constant dark environment that also contains no other time cues, and ‘approximately’ means that under constant dark conditions the endogenous rhythm is typically a little longer than 24 h
Light-at-night theory
In the mid-1980s, Stevens [11] proposed that increasing use of electric light-at-night (LAN) might explain part of the increasing incidence of breast cancer in industrial societies and the rapidly increasing risk in the developing world by suppressing melatonin production by the pineal gland; normally, melatonin production is 5–20 times higher at night in the dark than during the day, but this normal elevation at night will be suppressed by exposure to artificial light of sufficient intensity.
Shift work
One of the first and most obvious predictions of this theory was that shift working women would be at higher risk of breast cancer than day-working women [13]. Evidence has advanced to the point where the International Agency for Research on Cancer has concluded that “shift-work that involves circadian disruption is probably carcinogenic to humans (Group 2A)” [14]. This was based on a strong animal model [15], and a limited, but consistent group of epidemiological studies, many of which were of
Circadian genes and cancer epidemiology
As it has become clearer that the core circadian genes directly control the expression of a vast number of other genes, notably genes of cell cycle regulation and apoptosis, other mechanisms by which circadian disruption could increase risk of disease have become apparent [18], [19], [20]. If circadian disruption can cause cancer, then one obvious avenue of investigation is the association of markers of circadian gene function and risk [21], [22]. Specifically, Zhu et al. [23] speculated that
Early life experience and breast cancer
Since the seminal (or ovumal) paper by Trichopoulos [36], there has been growing interest in the possibility that early life experience, even beginning in utero, could affect lifetime risk of breast cancer. Combining this theory with the possibility that circadian disruption from altered lighting might increase risk yields the idea that a woman's light exposure during pregnancy (particularly from non-day shift work) might increase lifetime risk of breast cancer to her daughters, and that the
Discussion
If shift work does cause cancer then the mechanism is crucial to understand for the purposes of intervention and mitigation; shift work is not going to go away as more of world commerce operates on a 24 h basis. Given our advancing understanding of the biology of circadian rhythms and of how light affects the rhythm [40], the scientific and architectural lighting communities will work together to design shift schedules, and the lighting of non-day shift environments that better accommodate
Conflict of interest statement
The author declares that there are no conflicts of interest.
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