Light-at-night, circadian disruption and breast cancer: assessment of existing evidence
01 Aug 2009-International Journal of Epidemiology (Oxford University Press)-Vol. 38, Iss: 4, pp 963-970
TL;DR: If a consensus eventually emerges that LAN does increase risk, then the mechanisms for the effect are important to elucidate for intervention and mitigation and will provide for the development of lighting technologies at home and at work that minimize circadian disruption, while maintaining visual efficiency and aesthetics.
Abstract: Background Breast cancer incidence is increasing globally for largely unknown reasons. The possibility that a portion of the breast cancer burden might be explained by the introduction and increasing use of electricity to light the night was suggested >20 years ago.
Methods The theory is based on nocturnal light-induced disruption of circadian rhythms, notably reduction of melatonin synthesis. It has formed the basis for a series of predictions including that non-day shift work would increase risk, blind women would be at lower risk, long sleep duration would lower risk and community nighttime light level would co-distribute with breast cancer incidence on the population level.
Results Accumulation of epidemiological evidence has accelerated in recent years, reflected in an International Agency for Research on Cancer (IARC) classification of shift work as a probable human carcinogen (2A). There is also a strong rodent model in support of the light-at-night (LAN) idea.
Conclusion If a consensus eventually emerges that LAN does increase risk, then the mechanisms for the effect are important to elucidate for intervention and mitigation. The basic understanding of phototransduction for the circadian system, and of the molecular genetics of circadian rhythm generation are both advancing rapidly, and will provide for the development of lighting technologies at home and at work that minimize circadian disruption, while maintaining visual efficiency and aesthetics. In the interim, there are strategies now available to reduce the potential for circadian disruption, which include extending the daily dark period, appreciate nocturnal awakening in the dark, using dim red light for nighttime necessities, and unless recommended by a physician, not taking melatonin tablets.
Citations
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TL;DR: This study provides the first evidence of the implication of an ERA-circadian clock mechanism in the breast acinar morphogenetic process.
Abstract: Altered estrogen receptor α (ERA) signaling and altered circadian rhythms are both features of breast cancer. By using a method to entrain circadian oscillations in human cultured cells, we recently reported that the expression of key clock genes oscillates in a circadian fashion in ERA-positive breast epithelial cells but not in breast cancer cells, regardless of their ERA status. Moreover, we reported that ERA mRNA oscillates in a circadian fashion in ERA-positive breast epithelial cells, but not in ERA-positive breast cancer cells. By using ERA-positive HME1 breast epithelial cells, which can be both entrained in vitro and can form mammary gland-like acinar structures in three-dimensional (3D) culture, first we identified a circuit encompassing ERA and an estrogen-regulated loop consisting of two circadian clock genes, PER2 and BMAL1. Further, we demonstrated that this estrogen-regulated circuit is necessary for breast epithelial acinar morphogenesis. Disruption of this circuit due to ERA-knockdown, negatively affects the estrogen-sustained circadian PER2-BMAL1 mechanism as well as the formation of 3D HME1 acini. Conversely, knockdown of either PER2 or BMAL1, by hampering the PER2-BMAL1 loop of the circadian clock, negatively affects ERA circadian oscillations and 3D breast acinar morphogenesis. To our knowledge, this study provides the first evidence of the implication of an ERA-circadian clock mechanism in the breast acinar morphogenetic process.
30 citations
Cites background from "Light-at-night, circadian disruptio..."
...Apparently, women exposed to artificial light, or with jobs that can alter their circadian rhythms, are predisposed to breast cancer.(19) The peripheral effect of altered circadian rhythms in human breast would be due to the fact that the central clock can entrain peripheral clocks in tissues....
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TL;DR: The high 5 year correlation of melatonin levels implies that single measurements may be used to detect population level associations between melatonin and risk of cancer, and the need to record season of sample collection, and individual characteristics in order to maximize study power and prevent confounding.
Abstract: Melatonin, a marker for the circadian rhythm with serum levels peaking between 2AM and 5AM, is hypothesized to possess anti-cancer properties, making it a mechanistic candidate for the probable carcinogenic effect of circadian rhythm disruption. In order to weigh epidemiologic evidence on the association of melatonin with cancer, we must first understand the laboratory and biological sources of variability in melatonin levels measured in samples. Participants for this methodological study were men enrolled in the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO). We measured serum melatonin levels over a five year period in 97 individuals to test if melatonin levels are steady over time. The Pearson correlation coefficient between two measures separated by 1 year was 0.87, while the correlation between two measures separated by 5 years was to 0.70. In an additional cross-sectional study of 292 individuals, we used Analysis of Variance to identify differences in melatonin levels between different lifestyle and environmental characteristics. Serum melatonin levels were slightly higher in samples collected from 130 individuals during the winter, (6.36±0.59 pg/ml) than in samples collected from 119 individuals during the summer (4.83±0.62 pg/ml). Serum melatonin levels were lowest in current smokers (3.02±1.25 pg/ml, p = 0.007) compared to never (6.66±0.66 pg/ml) and former (5.59±0.50 pg/ml) smokers whereas BMI did not significantly affect serum melatonin levels in this study. In conclusion, the high 5 year correlation of melatonin levels implies that single measurements may be used to detect population level associations between melatonin and risk of cancer. Furthermore, our results reiterate the need to record season of sample collection, and individual characteristics in order to maximize study power and prevent confounding.
30 citations
29 May 2013
TL;DR: Exposure to alternating patterns of light and dark as experienced by millions of shift workers may produce long-lasting changes in both mammalian circadian and neurobehavioural systems.
Abstract: Disruption of circadian rhythms is associated with several deleterious health consequences and cognitive impairment. It is estimated that as many as one in five workers are exposed to this risk factor due to experiencing some degree of chronodisruption by way of recurring patterns of shift work. It is not presently clear therefore how efficiently the mammalian circadian system entrains to alternative light/dark cycles such as those found in shift work schedules. The present study examines male CD-1 mice exposed to three different paradigms of rapidly rotating shift work-like light/dark manipulations compared to control animals maintained on a standard 12:12 h light/dark cycle. Analysis of circadian patterns of behaviour under such conditions reveals that for fast rotating schedules of light/dark there is minimal circadian entrainment. Further, when placed in constant conditions after a period under the “shift work” lighting conditions there were changes to circadian period associated with the shift work schedules. In contrast to previous studies the shift work-like conditions did not produce changes in animal body-weight. Behavioural testing suggests possible anxiogenic and hyperactive outcomes dependent on rotation speed as animals displayed open field thigmotaxis and hyperlocomotion. These results indicate that exposure to alternating patterns of light and dark as experienced by millions of shift workers may produce long-lasting changes in both mammalian circadian and neurobehavioural systems.
29 citations
Cites background from "Light-at-night, circadian disruptio..."
...Further, given the key role melatonin may play (for example in the “light-atnight” hypothesis [43]) it is worth noting that CD-1 mice, like nearly all laboratory mouse species, do not synthesise melatonin, and so there may be differences in melatoninproducing rodents....
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TL;DR: The prediction that within the state of Connecticut, USA, communities with high nighttime outdoor light level would have higher breast cancer incidence rates was confirmed; the association was strongest among premenopausal women.
29 citations
TL;DR: A bi-objective model considering daytime preference is established to minimize the delayed workloads and the workloads in nights to improve working comfort, safety, and green and energy-savings degrees.
27 citations
Cites background from "Light-at-night, circadian disruptio..."
...The possibility that a portion of the breast cancer burden might be explained by the introduction and increasing use of electricity to light the night more than 20 years ago (Stevens, 2009)....
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