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: Factors that may contribute to racial/ethnic differences in sleep including intra-ethnic variation, cultural biases, genetics and psychosocial factors are explored.
155 citations
TL;DR: The lack of an association between night-shift work and breast cancer adds to the inconsistent epidemiologic evidence and it may be premature to consider shift work a cause of cancer.
Abstract: Shift work involving disruption of circadian rhythms has been classified as a probable cause of human cancer by the International Agency for Research on Cancer, based on limited epidemiologic evidence and abundant experimental evidence. The authors investigated this association in a population-based prospective cohort study of Chinese women. At baseline (1996–2000), information on lifetime occupational history was obtained from 73,049 women. Lifetime night-shift exposure indices were created using a job exposure matrix. During 2002–2004, self-reported data on frequency and duration of night-shift work were collected. Hazard ratios and 95% confidence intervals, adjusted for major breast cancer risk factors, were calculated. During follow-up through 2007, 717 incident cases of breast cancer were diagnosed. Breast cancer risk was not associated with ever working the night shift on the basis of the job exposure matrix (adjusted hazard ratio = 1.0, 95% confidence interval: 0.9, 1.2) or self-reported history of night-shift work (adjusted hazard ratio = 0.9, 95% confidence interval: 0.7, 1.1). Risk was also not associated with frequency, duration, or cumulative amount of night-shift work. There were no indications of effect modification. The lack of an association between night-shift work and breast cancer adds to the inconsistent epidemiologic evidence. It may be premature to consider shift work a cause of cancer.
154 citations
TL;DR: A review article as mentioned in this paper discusses recent work on the melatonin-mediated circadian regulation and integration of molecular, dietary, and metabolic signaling mechanisms involved in human breast cancer growth and the consequences of circadian disruption by exposure to light at night (LAN).
Abstract: This review article discusses recent work on the melatonin-mediated circadian regulation and integration of molecular, dietary, and metabolic signaling mechanisms involved in human breast cancer growth and the consequences of circadian disruption by exposure to light at night (LAN). The antiproliferative effects of the circadian melatonin signal are mediated through a major mechanism involving the activation of MT(1) melatonin receptors expressed in human breast cancer cell lines and xenografts. In estrogen receptor (ERα+) human breast cancer cells, melatonin suppresses both ERα mRNA expression and estrogen-induced transcriptional activity of the ERα via MT(1) -induced activation of G(αi2) signaling and reduction of 3',5'-cyclic adenosine monophosphate (cAMP) levels. Melatonin also regulates the transactivation of additional members of the steroid hormone/nuclear receptor super-family, enzymes involved in estrogen metabolism, expression/activation of telomerase, and the expression of core clock and clock-related genes. The anti-invasive/anti-metastatic actions of melatonin involve the blockade of p38 phosphorylation and the expression of matrix metalloproteinases. Melatonin also inhibits the growth of human breast cancer xenografts via another critical pathway involving MT(1) -mediated suppression of cAMP leading to blockade of linoleic acid uptake and its metabolism to the mitogenic signaling molecule 13-hydroxyoctadecadienoic acid (13-HODE). Down-regulation of 13-HODE reduces the activation of growth factor pathways supporting cell proliferation and survival. Experimental evidence in rats and humans indicating that LAN-induced circadian disruption of the nocturnal melatonin signal activates human breast cancer growth, metabolism, and signaling provides the strongest mechanistic support, thus far, for population and ecological studies demonstrating elevated breast cancer risk in night shift workers and other individuals increasingly exposed to LAN.
149 citations
TL;DR: A significant positive association between population LAN level and incidence rates of breast cancer is found and provides coherence of the previously reported case–control and cohort studies with the co-distribution of LAN and breast cancer in entire populations.
Abstract: Breast cancer incidence varies widely among countries of the world for largely unknown reasons. We investigated whether country-level light at night (LAN) is associated with incidence. We compared incidence rates of five common cancers in women (breast, lung, colorectal, larynx, and liver), observed in 164 countries of the world from the GLOBOCAN database, with population-weighted country-level LAN, and with several developmental and environmental indicators, including fertility rate, per capita income, percent of urban population, and electricity consumption. Two types of regression models were used in the analysis: Ordinary Least Squares and Spatial Errors. We found a significant positive association between population LAN level and incidence rates of breast cancer. There was no such an association between LAN level and colorectal, larynx, liver, and lung cancers. A sensitivity test, holding other variables at their average values, yielded a 30–50% higher risk of breast cancer in the highest LAN exposed countries compared to the lowest LAN exposed countries. The possibility that under-reporting from the registries in the low-resource, and also low-LAN, countries created a spurious association was evaluated in several ways and shown not to account for the results. These findings provide coherence of the previously reported case–control and cohort studies with the co-distribution of LAN and breast cancer in entire populations.
144 citations
Cites background or result from "Light-at-night, circadian disruptio..."
...The results of the present study are consistent with those of previous studies of LAN and risk [1], and those obtained on a national scale of breast cancer incidence in Israel [26]....
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...There is evidence that excessive exposure to light at night (LAN) may increase the risk of breast cancer (reviewed in [1, 2])....
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TL;DR: Investigating the risk of night work in a German population-based case-control study found that long-term night work was associated with a modestly, but not significantly, increased breast cancer risk, while having ever done nightWork was not.
Abstract: Objectives Some epidemiological and animal data indicate that night work might increase the risk for breast cancer. We have investigated the risk in a German population-based case–control study known as GENICA (gene environment interaction and breast cancer).
Methods The GENICA study involved interviews to assess shift work information in 857 breast cancer cases and 892 controls. We estimated risks of employment status and night shift characteristics using conditional logistic regression models, adjusting for potential confounders. Resampling and bootstrapping were applied to adjust the risk estimates for a potential selection bias.
Results Among 1749 women, 56 cases and 57 controls worked in night shifts for ≥1 year, usually in the healthcare sector (63.0% of controls). Female night workers were more frequently nulliparous and low-educated than day workers (28.6% versus 17.8% and 12.3% versus 9.2%, respectively). Fewer women in night work had ever used post-menopausal hormone therapy (35.7% versus 51.9%). An elevated breast cancer risk was not associated with having ever done shift or night work when compared to women employed in day work only [odds ratio (OR) 0.96, 95% confidence interval (95% CI) 0.67–1.38 and OR 0.91, 95% CI 0.55–1.49, respectively). Women who reported >807 night shifts, the third quartile of the distribution among controls, experienced a breast cancer risk of 1.73 (95% CI 0.71–4.22). Night work for ≥20 years was associated with an OR of 2.48 (95% CI 0.62–9.99) based on 12 cases and 5 controls.
Conclusions Long-term night work was associated with a modestly, but not significantly, increased breast cancer risk, while having ever done night work was not. The precision of the results was limited by a low prevalence of night work in this study population.
132 citations
Cites background from "Light-at-night, circadian disruptio..."
...It has been discussed that changes in melatonin levels caused by LAN might be related to the development of breast cancer (5, 6)....
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...The following articles refer to this text: 2010;36(2):163-179; 2010;36(2):81-84; 2012;38(6):590-599; 2012;38(6):553-559; 2013;39(2):170-177; 2013;39(5):448-455; 2013;39(5):431-447; 2014;40(3):295-304; 2014;40(5):502-510; 2017;43(1):59-67...
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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.
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