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.
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TL;DR: A literature review of the effects of human exposure to ALAN suggests that it is necessary to consider various characteristics of artificial light, beyond mere intensity, in order to understand the health effects of ALAN exposure.
Abstract: It has frequently been reported that exposure to artificial light at night (ALAN) may cause negative health effects, such as breast cancer, circadian phase disruption and sleep disorders. Here, we reviewed the literature assessing the effects of human exposure to ALAN in order to list the health effects of various aspects of ALAN. Several electronic databases were searched for articles, published through August 2014, related to assessing the effects of exposure to ALAN on human health; these also included the details of experiments on such exposure. A total of 85 articles were included in the review. Several observational studies showed that outdoor ALAN levels are a risk factor for breast cancer and reported that indoor light intensity and individual lighting habits were relevant to this risk. Exposure to artificial bright light during the nighttime suppresses melatonin secretion, increases sleep onset latency (SOL) and increases alertness. Circadian misalignment caused by chronic ALAN exposure may have ...
295 citations
Cites background from "Light-at-night, circadian disruptio..."
...Aside from cancer, sleep disturbance due to ALAN exposure may also have an impact on aging and metabolic processes (Hood et al., 2004; Stevens et al., 2007), as well as on heart disease, diabetes, mood disorders and obesity, which have become pandemic (Gangwisch, 2014; Stevens, 2009)....
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TL;DR: Elucidation of the role of clockwork disruption, such as exposure to light at night and sleep disruption, in cancer biology could be important in developing new targeted anticancer therapies, optimizing individualized chronotherapy and modifying lighting environment in workplaces or homes.
Abstract: Circadian rhythms show universally a 24-h oscillation pattern in metabolic, physiological and behavioral functions of almost all species. This pattern is due to a fundamental adaptation to the rotation of Earth around its own axis. Molecular mechanisms of generation of circadian rhythms organize a biochemical network in suprachiasmatic nucleus and peripheral tissues, building cell autonomous clock pacemakers. Rhythmicity is observed in transcriptional expression of a wide range of clock-controlled genes that regulate a variety of normal cell functions, such as cell division and proliferation. Desynchrony of this rhythmicity seems to be implicated in several pathologic conditions, including tumorigenesis and progression of cancer. In 2007, the International Agency for Research on Cancer (IARC) categorized “shiftwork that involves circadian disruption (as) probably carcinogenic to humans” (Group 2A in the IARC classification system of carcinogenic potency of an agentagent) (Painting, Firefighting, and Shiftwork; IARC; 2007). This review discusses the potential relation between disruptions of normal circadian rhythms with genetic driving machinery of cancer. Elucidation of the role of clockwork disruption, such as exposure to light at night and sleep disruption, in cancer biology could be important in developing new targeted anticancer therapies, optimizing individualized chronotherapy and modifying lighting environment in workplaces or homes.
265 citations
TL;DR: If electric light at night does explain a portion of the breast cancer burden, then there are practical interventions that can be implemented, including more selective use of light and the adoption of recent advances in lighting technology and application.
Abstract: Breast cancer is the leading cause of cancer death among women worldwide, and there is only a limited explanation of why. Risk is highest in the most industrialized countries but also is rising rapidly in the developing world. Known risk factors account for only a portion of the incidence in the high-risk populations, and there has been considerable speculation and many false leads on other possibly major determinants of risk, such as dietary fat. A hallmark of industrialization is the increasing use of electricity to light the night, both within the home and without. It has only recently become clear that this evolutionarily new and, thereby, unnatural exposure can disrupt human circadian rhythmicity, of which three salient features are melatonin production, sleep, and the circadian clock. A convergence of research in cells, rodents, and humans suggests that the health consequences of circadian disruption may be substantial. An innovative experimental model has shown that light at night markedly increases the growth of human breast cancer xenografts in rats. In humans, the theory that light exposure at night increases breast cancer risk leads to specific predictions that are being tested epidemiologically: evidence has accumulated on risk in shift workers, risk in blind women, and the impact of sleep duration on risk. If electric light at night does explain a portion of the breast cancer burden, then there are practical interventions that can be implemented, including more selective use of light and the adoption of recent advances in lighting technology and application.
263 citations
Cites background or result from "Light-at-night, circadian disruptio..."
...Subsequent results have been mixed, so the evidence to date is inconclusive.(105) In particular, Girschik et al(125)...
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...exists on circadian disruption in prostate cancer than breast cancer, but there is some limited evidence.(105) In a prospective study conducted in Iceland, Sigurdardottir et al(147) focused on...
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...In general, predictions of the theory have been supported.(105)...
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TL;DR: It is shown that cloud coverage dramatically amplifies the sky luminance, and inside of the city overcast nights are brighter than clear rural moonlit nights, which have important implications for choronobiological and chronoecological studies in urban areas, where this amplification effect has been considered.
Abstract: The diurnal cycle of light and dark is one of the strongest environmental factors for life on Earth. Many species in both terrestrial and aquatic ecosystems use the level of ambient light to regulate their metabolism, growth, and behavior. The sky glow caused by artificial lighting from urban areas disrupts this natural cycle, and has been shown to impact the behavior of organisms, even many kilometers away from the light sources. It could be hypothesized that factors that increase the luminance of the sky amplify the degree of this “ecological light pollution”. We show that cloud coverage dramatically amplifies the sky luminance, by a factor of 10.1 for one location inside of Berlin and by a factor of 2.8 at 32 km from the city center. We also show that inside of the city overcast nights are brighter than clear rural moonlit nights, by a factor of 4.1. These results have important implications for choronobiological and chronoecological studies in urban areas, where this amplification effect has previously not been considered.
237 citations
TL;DR: The evidence for the pervasive effects of circadian disruption in humans and animal models is reviewed, drawing from both environmental and genetic studies, and questions for future research are identified.
Abstract: Daily rhythms in behavior and physiology are programmed by a hierarchical collection of biological clocks located throughout the brain and body, known as the circadian system. Mounting evidence indicates that disruption of circadian regulation is associated with a wide variety of adverse health consequences, including increased risk for premature death, cancer, metabolic syndrome, cardiovascular dysfunction, immune dysregulation, reproductive problems, mood disorders, and learning deficits. Here we review the evidence for the pervasive effects of circadian disruption in humans and animal models, drawing from both environmental and genetic studies, and identify questions for future research.
232 citations
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TL;DR: This paper contrasts Bradford Hill’s approach with a currently fashionable framework for reasoning about statistical associations – the Common Task Framework – and suggests why following Bradford Hill, 50+ years on, is still extraordinarily reasonable.
Abstract: In 1965, Sir Austin Bradford Hill offered his thoughts on: “What aspects of [an] association should we especially consider before deciding that the most likely interpretation of it is causation?” He proposed nine means for reasoning about the association, which he named as: strength, consistency, specificity, temporality, biological gradient, plausibility, coherence, experiment, and analogy. In this paper, we look at what motivated Bradford Hill to propose we focus on these nine features. We contrast Bradford Hill’s approach with a currently fashionable framework for reasoning about statistical associations – the Common Task Framework. And then suggest why following Bradford Hill, 50+ years on, is still extraordinarily reasonable.
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TL;DR: It is shown that retinal ganglion cells innervating the SCN are intrinsically photosensitive, and depolarized in response to light even when all synaptic input from rods and cones was blocked.
Abstract: Light synchronizes mammalian circadian rhythms with environmental time by modulating retinal input to the circadian pacemaker-the suprachiasmatic nucleus (SCN) of the hypothalamus. Such photic entrainment requires neither rods nor cones, the only known retinal photoreceptors. Here, we show that retinal ganglion cells innervating the SCN are intrinsically photosensitive. Unlike other ganglion cells, they depolarized in response to light even when all synaptic input from rods and cones was blocked. The sensitivity, spectral tuning, and slow kinetics of this light response matched those of the photic entrainment mechanism, suggesting that these ganglion cells may be the primary photoreceptors for this system.
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TL;DR: Findings establish that the human response to light is qualitatively similar to that of other mammals.
Abstract: Bright artificial light suppressed nocturnal secretion of melatonin in six normal human subjects. Room light of less intensity, which is sufficient to suppress melatonin secretion in other mammals, failed to do so in humans. In contrast to the results of previous experiments in which ordinary room light was used, these findings establish that the human response to light is qualitatively similar to that of other mammals.
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TL;DR: The results suggest that, in humans, a single photopigment may be primarily responsible for melatonin suppression, and its peak absorbance appears to be distinct from that of rod and cone cellphotopigments for vision.
Abstract: The photopigment in the human eye that transduces light for circadian and neuroendocrine regulation, is unknown. The aim of this study was to establish an action spectrum for light-induced melatonin suppression that could help elucidate the ocular photoreceptor system for regulating the human pineal gland. Subjects (37 females, 35 males, mean age of 24.5 +/- 0.3 years) were healthy and had normal color vision. Full-field, monochromatic light exposures took place between 2:00 and 3:30 A.M. while subjects' pupils were dilated. Blood samples collected before and after light exposures were quantified for melatonin. Each subject was tested with at least seven different irradiances of one wavelength with a minimum of 1 week between each nighttime exposure. Nighttime melatonin suppression tests (n = 627) were completed with wavelengths from 420 to 600 nm. The data were fit to eight univariant, sigmoidal fluence-response curves (R(2) = 0.81-0.95). The action spectrum constructed from these data fit an opsin template (R(2) = 0.91), which identifies 446-477 nm as the most potent wavelength region providing circadian input for regulating melatonin secretion. The results suggest that, in humans, a single photopigment may be primarily responsible for melatonin suppression, and its peak absorbance appears to be distinct from that of rod and cone cell photopigments for vision. The data also suggest that this new photopigment is retinaldehyde based. These findings suggest that there is a novel opsin photopigment in the human eye that mediates circadian photoreception.
1,708 citations