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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...The precise mechanisms of cancer prevention remain to be elucidated (Stevens, 2009)....
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TL;DR: A framework that focuses on the cross‐factoring of the ways in which artificial lighting alters natural light regimes (spatially, temporally, and spectrally), and the ways that light influences biological systems, particularly the distinction between light as a resource and light as an information source is proposed.
Abstract: The ecological impacts of nighttime light pollution have been a longstanding source of concern, accentuated by realized and projected growth in electrical lighting. As human communities and lighting technologies develop, artificial light increasingly modifies natural light regimes by encroaching on dark refuges in space, in time, and across wavelengths. A wide variety of ecological implications of artificial light have been identified. However, the primary research to date is largely focused on the disruptive influence of nighttime light on higher vertebrates, and while comprehensive reviews have been compiled along taxonomic lines and within specific research domains, the subject is in need of synthesis within a common mechanistic framework. Here we propose such a framework that focuses on the cross-factoring of the ways in which artificial lighting alters natural light regimes (spatially, temporally, and spectrally), and the ways in which light influences biological systems, particularly the distinction between light as a resource and light as an information source. We review the evidence for each of the combinations of this cross-factoring. As artificial lighting alters natural patterns of light in space, time and across wavelengths, natural patterns of resource use and information flows may be disrupted, with downstream effects to the structure and function of ecosystems. This review highlights: (i) the potential influence of nighttime lighting at all levels of biological organisation (from cell to ecosystem); (ii) the significant impact that even low levels of nighttime light pollution can have; and (iii) the existence of major research gaps, particularly in terms of the impacts of light at population and ecosystem levels, identification of intensity thresholds, and the spatial extent of impacts in the vicinity of artificial lights.
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...Exposure to light at night has been shown to disrupt the circadian cycle of hormone production in humans, particularly melatonin, which has been linked to an increase in cancer risk in shift-workers (Stevens, 1987, 2009; Megdal et al., 2005; Reiter et al., 2011)....
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TL;DR: Findings on shift work, in relation to risks of CVD, metabolic syndrome and diabetes are also suggestive but not conclusive for an adverse relationship, making it difficult to draw general conclusions.
Abstract: Background Shift work, including night work, has been hypothesized to increase the risk of chronic diseases, including cancer, cardiovascular disease (CVD), metabolic syndrome and diabetes. Recent reviews of evidence relating to these hypotheses have focussed on specific diseases or potential mechanisms, but no general summary of the current data on shift work and chronic disease has been published.
Methods Systematic and critical reviews and recent original studies indexed in PubMed prior to 31 December 2009 were retrieved, aided by manual searches of reference lists. The main conclusions from reviews and principle results from recent studies are presented in text and tables.
Results Published evidence is suggestive but not conclusive for an adverse association between night work and breast cancer but limited and inconsistent for cancers at other sites and all cancers combined. Findings on shift work, in relation to risks of CVD, metabolic syndrome and diabetes are also suggestive but not conclusive for an adverse relationship.
Conclusions Heterogeneity of study exposures and outcomes and emphasis on positive but non-significant results make it difficult to draw general conclusions. Further data are needed for additional disease endpoints and study populations.
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...It has also been concluded that ‘shift work that involves circadian disruption is probably carcinogenic to humans’ (Straif et al., 2007) and can lead to higher incidence of cardiovascular disease and obesity (Karlsson et al., 2001; Stevens, 2009)....
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References
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TL;DR: Evidence is provided that exposure to visible light, including artificial light, suppresses the normal nocturnal production of melatonin by the pineal gland, which supports a hypothesis that light at night may be a potential risk factor of breast cancer.
Abstract: Breast cancer is the most commonly diagnosed female noncutaneous cancer in the United States and in Europe. The etiology of breast cancer is primarily unknown, with an estimated one quarter of all breast cancers possibly due to heritable factors (1) and only a minor proportion possibly due to already established environmental risk factors, such as early age at menarche, older age at first pregnancy, and delayed menopause (2). Because the incidence of breast cancer in many countries is increasing, for unclear reasons, it is not surprising that society is demanding explanations for the increased incidence of the disease and that researchers are searching for new causes. One avenue of research has been the so-called “man-made endocrine disrupting chemicals,” such as 2-(chlorphenyl)-2-(4-chlorphenyl)-1,1,1-trichlorethan (DDT), polychlorinated biphenyls, or nonyl phenols (3). So far, however, the results from this research have been sparse in expanding our knowledge about risk factors for breast cancer. In this issue of the Journal, two independent epidemiologic studies by Davis et al. (4) and Schernhammer et al. (5) have provided evidence about another potential risk factor, light at night. These studies (4,5) support a hypothesis published about 10 years ago by the former group that light at night may be a potential risk factor of breast cancer (6,7). The scientific rationale behind this intriguing hypothesis is that exposure to visible light, including artificial light, suppresses the normal nocturnal production of melatonin by the pineal gland (6). Melatonin is a mammalian hormone involved in circadian rhythms and sleep and potentially in restraining tumor growth (8). The synthesis and release of melatonin occur in a dose–response-like manner that is stimulated by darkness and inhibited by light through photic information from the retina. Peak melatonin levels normally occur during sleep in the middle of the night (8). Several experimental studies have provided evidence of an association between melatonin levels and risk of cancer. For example, evidence from rodent studies found that pinealectomy increased tumor growth (9), that administration of melatonin inhibited the promotion of chemically induced mammary tumors (9,10), and that constant light exposure had a growth-promoting effect on chemically induced tumors (11). Evidence in humans is less direct, although impaired pineal secretion of melatonin is associated with an increased release of estrogen by the ovaries (7,8), and low serum melatonin concentrations have been reported in women with estrogen receptorpositive breast cancer (8). In vitro, physiologic concentrations of melatonin inhibited the growth of human breast cancer cells
169 citations
TL;DR: Action spectra in humans show that the peak wavelength sensitivity for this newly discovered sensory system is within the blue portion of the spectrum, which opens the door to innovations in light therapy for circadian and affective disorders, as well as possible architectural light applications.
Abstract: Light profoundly impacts human consciousness through the stimulation of the visual system and powerfully regulates the human circadian system, which, in turn, has a broad regulatory impact on virtually all tissues in the body. For more than 25 years, the techniques of action spectroscopy have yielded insights into the wavelength sensitivity of circadian input in humans and other mammalian species. The seminal discovery of melanopsin, the photopigment in intrinsically photosensitive retinal ganglion cells, has provided a significant turning point for understanding human circadian phototransduction. Action spectra in humans show that the peak wavelength sensitivity for this newly discovered sensory system is within the blue portion of the spectrum. This is fundamentally different from the three-cone photopic visual system, as well as the individual rod and cone photoreceptor peaks. Studies on rodents, nonhuman primates, and humans indicate that despite having a different wavelength fingerprint, these classic visual photoreceptors still provide an element of input to the circadian system. These findings open the door to innovations in light therapy for circadian and affective disorders, as well as possible architectural light applications.
168 citations
Journal Article•
TL;DR: It is concluded that, to have an impressive antitumor effect, presence of the pineal gland is essential, and the probable site of melatonin action appears to be at both the Pineal gland and the hypothalamus.
Abstract: Exposure of female Holtzman rats to constant light (24 hr/day) immediately after birth significantly increased 9,10-dimethyl-1,2-benzanthracene-induced mammary cancer. Such “functionally pinealectomized” animals also revealed significant increase in the circulating level of prolactin and exaggerated development and proliferative activity of mammary epithelium, as measured by quantitation of terminal end buds and alveolar buds from the whole mounts and by DNA synthesis, respectively. Administration of melatonin (500 µg/day/rat i.p. given from 52 to 145 days of age) completely abolished the effect of functional pinealectomy by sharply reducing 9,10-dimethyl-1,2-benzanthracene-induced cancer incidence from 95% to 25% during the post-9,10-dimethyl-1,2-benzanthracene observation period which lasted up to 180 days. On the other hand, administration of melatonin to surgically pinealectomized animals exposed to constant light reversed the effect only partially by reducing the cancer incidence from 83% to 53%. Further, melatonin treatment in intact and surgically pinealectomized animals exposed to a short photoperiod revealed qualitatively similar differences in suppression of the cancer incidence. From these results, it is concluded that, to have an impressive antitumor effect, presence of the pineal gland is essential, and the probable site of melatonin action appears to be at both the pineal gland and the hypothalamus.
167 citations
TL;DR: The overwhelming evidence that melanopsin serves as the photopigment in these cells is summarized and the emerging evidence that the downstream signaling cascade, including the light-gated channel, might resemble those found in rhabdomeric invertebrate photoreceptors is reviewed.
Abstract: A third class of photoreceptors has recently been identified in the mammalian retina. They are a rare cell type within the class of ganglion cells, which are the output cells of the retina. These intrinsically photosensitive retinal ganglion cells support a variety of physiological responses to daylight, including synchronization of circadian rhythms, modulation of melatonin release, and regulation of pupil size. The goal of this review is to summarize what is currently known concerning the cellular and biochemical basis of phototransduction in these cells. I summarize the overwhelming evidence that melanopsin serves as the photopigment in these cells and review the emerging evidence that the downstream signaling cascade, including the light-gated channel, might resemble those found in rhabdomeric invertebrate photoreceptors.
164 citations
TL;DR: No evidence was found for an association between shift work and breast or prostate cancer, or all cancer sites combined among shift workers.
Abstract: Objectives Melatonin, a hormone that inhibits experimentally induced cancers, is suppressed by nighttime exposure to light so that nighttime shift workers may be at an increased risk of cancer. Previous studies of shift workers found an increased risk of breast cancer among women and suggested a possible increased risk of colon cancer among women and prostate cancer. The present study was conducted to see whether these previous findings could be confirmed and whether shift workers are at elevated risk for cancer at additional sites.
Methods Altogether 2 102 126 male and 1 148 661 female workers were identified who worked in both 1960 and 1970. Their jobs were classified according to the percentage of shift workers, and they were followed from 1971 through 1989 or until they were diagnosed with cancer or died. Standardized incidence ratios (SIR) were used to compare the adjusted cancer incidence rates for shift workers with those for nonshift workers.
Results Cancer rates were not elevated for the male shift workers [all sites combined: N=6524 cases among shift workers, SIR 1.02, 95% confidence interval (95% CI) 1.00–1.05; prostate: N=1319, SIR 1.04, 95% CI 0.99–1.10] or for the female shift workers (all sites combined: N=268, SIR 1.00, 95% CI 0.89–1.13; breast: N=70 cases, SIR 0.94, 95% CI 0.74–1.18).
Conclusions No evidence was found for an association between shift work and breast or prostate cancer, or all cancer sites combined among shift workers.
155 citations