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.
706 citations
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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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...responsible for the rise in breast cancer incidence seen in the industrialized world [3]....
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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: These mechanistic studies are the first to provide a rational biological explanation for the increased breast cancer risk in female night shift workers and show that the tumor growth response to exposure to light during darkness is intensity dependent and that the human nocturnal, circadian melatonin signal not only inhibits human breast cancer growth but that this effect is extinguished by short-term ocular exposure to bright, white light at night.
Abstract: The increased breast cancer risk in female night shift workers has been postulated to result from the suppression of pineal melatonin production by exposure to light at night. Exposure of rats bearing rat hepatomas or human breast cancer xenografts to increasing intensities of white fluorescent light during each 12-hour dark phase (0-345 MW/cm 2 ) resulted in a dose-dependent suppression of nocturnal melatonin blood levels and a stimulation of tumor growth and linoleic acid uptake/metabolism to the mitogenic molecule 13-hydroxyoctadecadienoic acid. Venous blood samples were collected from healthy, premenopausal female volunteers during either the daytime, nighttime, or nighttime following 90 minutes of ocular bright, white fluorescent light exposure at 580 MW/cm 2 (i.e., 2,800 lx). Compared with tumors perfused with daytimecollected melatonin-deficient blood, human breast cancer xenografts and rat hepatomas perfused in situ, with nocturnal, physiologically melatonin-rich blood collected during the night, exhibited markedly suppressed proliferative activity and linoleic acid uptake/metabolism. Tumors perfused with melatonin-deficient blood collected following ocular exposure to light at night exhibited the daytime pattern of high tumor proliferative activity. These results are the first to show that the tumor growth response to exposure to light during darkness is intensity dependent and that the human nocturnal, circadian melatonin signal not only inhibits human breast cancer growth but that this effect is extinguished by short-term ocular exposure to bright, white light at night. These mechanistic studies are the first to provide a rational biological explanation for the increased breast cancer risk in female night shift workers. (Cancer Res 2005; 65(23): 11174-84)
378 citations
TL;DR: This report is the first known to reveal a significant relation between rotating-shift work and prostate cancer.
Abstract: Shift workers have been reported to have an increased risk of some cancers. However, the risk of prostate cancer in shift workers is not known to have been examined previously. This study prospectively examined the association between shift work and risk of prostate cancer incidence among 14,052 working men in Japan enrolled in a large-scale prospective cohort. A baseline survey was conducted between 1988 and 1990. Subjects were asked to indicate the most regular work schedule they had undertaken previously: day work, rotating-shift work, or fixed-night work. During 111,974 person-years, 31 cases of prostate cancer were recorded. The Cox proportional hazards model was used to estimate the risk, with adjustments for age, family history of prostate cancer, study area surveyed, body mass index, smoking, alcohol drinking, job type, physical activity at work, workplace, perceived stress, educational level, and marriage status. Compared with day workers, rotating-shift workers were significantly at risk for prostate cancer (relative risk = 3.0, 95% confidence interval: 1.2, 7.7), whereas fixed-night work was associated with a small and nonsignificant increase in risk. This report is the first known to reveal a significant relation between rotating-shift work and prostate cancer.
375 citations
TL;DR: The past 20 years of research have identified several risk and protective factors for breast cancer that can be understood as measures of the cumulative exposure of the breast to estrogen and, perhaps, progesterone.
Abstract: The past 20 years of research have identified several risk and protective factors for breast cancer. All these factors can be understood as measures of the cumulative exposure of the breast to estrogen and, perhaps, progesterone. These ovarian hormones affect the rate of cell division and thus manifest their effect on the risk of breast cancer by causing proliferation of breast epithelial cells (1). Proliferating cells are susceptible to genetic errors during DNA replication, which, if uncorrected, can ultimately lead to a malignant phenotype.
364 citations
TL;DR: It is suggested that the circadian system's sensitivity to light can be affected by a recent change in light history, as assessed by the magnitude of the suppression of melatonin secretion by nocturnal light.
Abstract: We investigated the impact of light exposure history on light sensitivity in humans, as assessed by the magnitude of the suppression of melatonin secretion by nocturnal light. The hypothesis was that following a week of increased daytime bright-light exposure, subjects would become less sensitive to light, and that after a week of restriction to dimmer light they would become more sensitive. During the bright week, subjects (n = 12) obtained 4.3 +/- 0.4 hr of bright light per day (by going outside and using light boxes indoors). During the dim week, they wore dark goggles (about 2% light transmission) when outside during daylight and spent 1.4 +/- 0.9 hr per day outside. Saliva samples were obtained every 30 min for 7 hr in dim light (<15 lux) on two consecutive nights (baseline and test night) at the end of each week. On the test night, 500 lux was presented for 3 hr in the middle of the collection period to suppress melatonin. There was significantly more suppression after the dim week compared with after the bright week (to 53 versus 41% of the baseline night values, P < 0.05). However, there were large individual differences, and the difference between the bright and dim weeks was most pronounced in seven of the 12 subjects. Possible reasons for these individual differences are discussed, including the possibility that 1 wk was not long enough to change light sensitivity in some subjects. In conclusion, this study suggests that the circadian system's sensitivity to light can be affected by a recent change in light history.
363 citations