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Journal ArticleDOI

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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Citations
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Journal ArticleDOI
TL;DR: Results show that 1-hour and 2-hour exposure to light from self-luminous devices significantly suppressed melatonin by approximately 23% and 38% respectively, suggesting that adolescents may be more sensitive to light than other populations.
Abstract: Self-luminous devices, such as computers, tablets and cell phones can emit short-wavelength (blue) light, which maximally suppresses melatonin. Melatonin is a hormone that starts rising approximately 2 hours prior to natural bedtimes and signals darkness and sleep to the body. The present study extends from previously published studies showing that light from self-luminous devices suppresses melatonin and delays sleep. This is the first study conducted in the home environment that investigated the effects of self-luminous devices on melatonin levels in adolescents (age 15–17 years). Results show that 1-hour and 2-hour exposure to light from self-luminous devices significantly suppressed melatonin by approximately 23% and 38% respectively. Compared to our previous studies, these results suggest that adolescents may be more sensitive to light than other populations.

73 citations

Journal ArticleDOI
TL;DR: Melatonin given in nocturnal drinking water prevented the adverse effect of the constant illumination (LL) and natural light (NL) regimens on the homeostasis, life span, and tumor development both in mice and rats.
Abstract: Light-at-night has become an increasing and essential part of the modern lifestyle and leads to a number of health problems, including excessive body mass index, cardiovascular diseases, diabetes, and cancer. The International Agency for Research on Cancer (IARC) Working Group concluded that "shift-work that involves circadian disruption is probably carcinogenic to humans" (Group 2A) [1]. According to the circadian disruption hypothesis, light-at-night might disrupt the endogenous circadian rhythm and specifically suppress nocturnal production of the pineal hormone melatonin and its secretion into the blood. We evaluated the effect of various light/dark regimens on the survival, life span, and spontaneous and chemical carcinogenesis in rodents. Exposure to constant illumination was followed by accelerated aging and enhanced spontaneous tumorigenesis in female CBA and transgenic HER-2/neu mice. In male and female rats maintained at various light/dark regimens (standard 12:12 light/dark [LD], the natural light [NL] of northwestern Russia, constant light [LL], and constant darkness [DD]) from the age of 25 days until natural death, it was found that exposure to NL and LL regimens accelerated age-related switch-off of the estrous function (in females), induced development of metabolic syndrome and spontaneous tumorigenesis, and shortened life span both in male and females rats compared to the standard LD regimen. Melatonin given in nocturnal drinking water prevented the adverse effect of the constant illumination (LL) and natural light (NL) regimens on the homeostasis, life span, and tumor development both in mice and rats. The exposure to the LL regimen accelerated colon carcinogenesis induced by 1,2-dimethylhydrazine (DMH) in rats, whereas the treatment with melatonin alleviated the effects of LL. The maintenance of rats at the DD regimen inhibited DMH-induced carcinogenesis. The LL regimen accelerated, whereas the DD regimen inhibited both mammary carcinogenesis induced by N-nitrosomethylurea and transplacental carcinogenesis induced by N-nitrosoethylurea in rats. Treatment with melatonin prevented premature aging and tumorigenesis in rodents. The data found in the literature and our observations suggest that the use of melatonin would be effective for cancer prevention in humans at risk as a result of light pollution.

73 citations

Journal ArticleDOI
TL;DR: The arguments of the LAN theory are revisited and put them into perspective regarding circadian physiology, physical likelihood (e.g., what intensities reach the retina), and potential risks, specifically in non-shiftworkers.
Abstract: In 2007, the IARC (WHO) has classified "shift-work that involves circadian disruption" as potentially carcinogenic. Ample evidence leaves no doubt that shift-work is detrimental for health, but the mechanisms behind this effect are not well understood. The hormone melatonin is often considered to be a causal link between night shift and tumor development. The underlying "light-at-night" (LAN) hypothesis is based on the following chain of arguments: melatonin is a hormone produced under the control of the circadian clock at night, and its synthesis can be suppressed by light; as an indolamine, it potentially acts as a scavenger of oxygen radicals, which in turn can damage DNA, which in turn can cause cancer. Although there is no experimental evidence that LAN is at the basis of increased cancer rates in shiftworkers, the scenario "light at night can cause cancer" influences research, medicine, the lighting industry and (via the media) also the general public, well beyond shiftwork. It is even suggested that baby-lights, TVs, computers, streetlights, moonlight, emergency lights, or any so-called "light pollution" by urban developments cause cancer via the mechanisms proposed by the LAN hypothesis. Our commentary addresses the growing concern surrounding light pollution. We revisit the arguments of the LAN theory and put them into perspective regarding circadian physiology, physical likelihood (e.g., what intensities reach the retina), and potential risks, specifically in non-shiftworkers.

73 citations


Cites background from "Light-at-night, circadian disruptio..."

  • ...…and tumor development in terms of “chronodisruption” (Erren et al., 2008; Haus, 2007), as currently proposed by the “light-at-night” (LAN) hypothesis (Stevens, 2009), based principally on the following facts: . melatonin is a hormone produced under the control of the circadian clock at night; .…...

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Journal ArticleDOI
TL;DR: This systematic review provides a comprehensive update on epidemiologic evidences on circadian disruption and prostate cancer since the last review published in 2012 and identified 12 new studies evaluating the effects of several circadian disruptors such as night shift work, sleep patterns, and circadian genes in prostate cancer risk.
Abstract: Since the publication of the International Agency for Research on Cancer Monograph in 2007 classifying night shift work leading to a disruption of circadian rhythm as probably carcinogenic to humans, there is an increasingly growing interest in understanding how circadian disruption may play a role in cancer development.This systematic review provides a comprehensive update on epidemiologic evidences on circadian disruption and prostate cancer since the last review published in 2012. We identified 12 new studies evaluating the effects of several circadian disruptors such as night shift work, sleep patterns, and circadian genes in prostate cancer risk. In contrast, no new studies have focused on exposure to light at night.Several convincing and biologically plausible hypotheses have been proposed to understand how circadian disruption may be related to cancer. However, the current difficulty of concluding on the role of circadian disruption on prostate cancer risk requires further studies including a better characterization of the different night shift systems, data on sleep patterns and chronotype, measurement of biomarkers, and investigations of polymorphisms in the genes regulating the biological clock. Cancer Epidemiol Biomarkers Prev; 26(7); 985-91. ©2017 AACR.

73 citations

Journal ArticleDOI
TL;DR: Exposure to dALAN during sleep increases the frequency of arousals, amount of shallow sleep and amount of REM sleep, and affects sleep structure, which suggests adverse effects of dALan during sleep on sleep quality and suggests the need to avoid exposure during sleep.
Abstract: Exposure to artificial light at night (ALAN) has become increasing common, especially in developed countries. We investigated the effect of dALAN exposure during sleep in healthy young male subjects. A total of 30 healthy young male volunteers from 21 to 29 years old were recruited for the study. They were randomly divided into two groups depending on light intensity (Group A: 5 lux and Group B: 10 lux). After a quality control process, 23 healthy subjects were included in the study (Group A: 11 subjects, Group B: 12 subjects). Subjects underwent an NPSG session with no light (Night 1) followed by an NPSG session randomly assigned to two different dim light conditions (5 or 10 lux, dom λ: 501.4 nm) for a whole night (Night 2). We found significant sleep structural differences between Nights 1 and 2, but no difference between Groups A and B. Exposure to dALAN during sleep was significantly associated with increased wake time after sleep onset (WASO; F = 7.273, p = 0.014), increased Stage N1 (F = 4.524, p = 0.045), decreased Stage N2 (F = 9.49, p = 0.006), increased Stage R (F = 6.698, p = 0.017) and non-significantly decreased REM density (F = 4.102, p = 0.056). We found that dALAN during sleep affects sleep structure. Exposure to dALAN during sleep increases the frequency of arousals, amount of shallow sleep and amount of REM sleep. This suggests adverse effects of dALAN during sleep on sleep quality and suggests the need to avoid exposure to dALAN during sleep.

73 citations


Cites background from "Light-at-night, circadian disruptio..."

  • ...The growing prevalence of exposure to artificial light at night (ALAN) has influenced human life cycles (Stevens, 2009)....

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References
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Journal ArticleDOI
Hill Ab1
TL;DR: The criteria outlined in "The Environment and Disease: Association or Causation?" help identify the causes of many diseases, including cancers of the reproductive system.
Abstract: In 1965, Austin Bradford Hill published the article "The Environment and Disease: Association or Causation?" in the Proceedings of the Royal Society of Medicine. In the article, Hill describes nine criteria to determine if an environmental factor, especially a condition or hazard in a work environment, causes an illness. The article arose from an inaugural presidential address Hill gave at the 1965 meeting of the Section of Occupational Medicine of the Royal Society of Medicine in London, England. The criteria he established in the article became known as the Bradford Hill criteria and the medical community refers to them when determining whether an environmental condition causes an illness. The criteria outlined in "The Environment and Disease: Association or Causation?" help identify the causes of many diseases, including cancers of the reproductive system.

6,992 citations

Journal Article
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.

5,542 citations

Journal ArticleDOI
08 Feb 2002-Science
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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Journal ArticleDOI
12 Dec 1980-Science
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.

1,776 citations

Journal ArticleDOI
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