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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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Journal ArticleDOI
TL;DR: Light-at-night (LAN) induced circadian disruption of the nocturnal melatonin signal activates human breast cancer growth, metabolism, and signaling, providing the strongest mechanistic support, thus far, for epidemiological studies demonstrating the elevated breast cancer risk in night shift workers and other individuals increasingly exposed to LAN.
Abstract: This review article discusses recent work on the melatonin-mediated circadian regulation and integration of molecular and metabolic signaling mechanisms involved in human breast cancer growth and the associated consequences of circadian disruption by exposure to light-at-night (LAN). The anti-proliferative effects of the circadian melatonin signal are, in general, mediated through mechanisms involving the activation of MT1 melatonin receptors expressed in human breast cancer cell lines and xenografts. In estrogen receptor-positive (ERα+) human breast cancer cells, melatonin suppresses both ERα mRNA expression and estrogen-induced transcriptional activity of the ERα via MT1-induced activation of Gαi2 signaling and reduction of cAMP levels. Melatonin also regulates the transcriptional activity of additional members of the nuclear receptor super-family, enzymes involved in estrogen metabolism, 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 matrix metalloproteinase expression. Melatonin also inhibits the growth of human breast cancer xenografts via MT1-mediated suppression of cAMP leading to a blockade of linoleic acid (LA) 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. Finally, studies in both rats and humans indicate that light-at-night (LAN) induced circadian disruption of the nocturnal melatonin signal activates human breast cancer growth, metabolism, and signaling, providing the strongest mechanistic support, thus far, for epidemiological studies demonstrating the elevated breast cancer risk in night shift workers and other individuals increasingly exposed to LAN.

91 citations


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

  • ...Given that LAN can repress nighttime melatonin production in both humans and rodents, the numerous studies that show that melatonin inhibits the development and growth of experimental models of breast cancer, and that either surgical removal of the pineal gland or exposure to constant light stimulates mammary tumorigenesis in rodents [10, 12], it has been hypothesized that light exposure at night may represent a unique risk factor for breast cancer in industrialized societies via its ability to suppress the nocturnal production of melatonin by the pineal gland [43, 44]....

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Journal ArticleDOI
TL;DR: In this paper, the authors explored the risk of sleep disorder (SD)-induced cancer using nationwide population data and provided the evidence that people diagnosed with insomnia, parasomnia and OSA are at a higher risk of developing cancers to remind people to improve sleep quality.
Abstract: Purpose: Insomnia, parasomnia, and obstructive sleep apnea have been associated with a number of disease pathologies, but little is known about the relationship of these sleep disorders and cancer. The study explored the risk of sleep disorder (SD)-induced cancer using nationwide population data. Two million data from the National Health Insurance system of Taiwan was used to assess for the relationship. Patients and Methods: Patients with cancer as our cases and patients without cancer as our control group in 2001-20011. The study patients were traced back to seek the exposure risk factor of sleep disorders, which was divided into three categories: insomnia, obstructive sleep apnea (OSA) and parasomnia. Patients were selected excluding patients who had cancer prior to presenting with the sleep disorder and the person-year is less than 2 years. Each case was randomly matched with two cases with the same age, gender, and index year. Results: There were significantly increased risks of breast cancer in the patients with insomnia (AHR=1.73; 95% CI: 1.57-1.90), patients with parasomnia (AHR=2.76; 95% CI: 1.53-5.00), and patients with OSA (AHR=2.10; 95% CI: 1.16-3.80). Moreover, patients with parasomnia had significantly higher risk of developing oral cancer (AHR=2.71; 95% CI: 1.02-7.24) compared with patients without parasomnia. The risk of suffering from nasal cancer (AHR=5.96, 95% CI: 2.96-11.99) and prostate cancer (AHR=3.69, 95% CI: 1.98- 6.89) in patients with OSA was significantly higher than that of patients without OSA. Conclusions: Our findings provided the evidence that people diagnosed with insomnia, parasomnia and OSA are at a higher risk of developing cancers to remind people to improve sleep quality.

91 citations

Journal ArticleDOI
TL;DR: It was proposed in 1987 that increasing use of electricity to light the night accounts in part for the rising risk of breast cancer globally and predictions from the theory include: non-day shift work increases risk, blindness reduces risk, long sleep duration lowers risk, and population level community nighttime light level co-distributes with breast cancer incidence.
Abstract: Breast cancer incidence increases rapidly as societies industrialize. Many changes occur during the industrialization process, one of which is a dramatic alteration in the lighted environment from a sun-based system to an electricity-based system. Increasingly, the natural dark period at night is being seriously eroded for the bulk of humanity. Based on the fact that light during the night can suppress melatonin, and also disrupt the circadian rhythm, it was proposed in 1987 that increasing use of electricity to light the night accounts in part for the rising risk of breast cancer globally. Predictions from the theory include: non-day shift work increases risk, blindness lowers risk, long sleep duration lowers risk, and population level community nighttime light level co-distributes with breast cancer incidence. Thus far, studies of these predictions are consistent in support of the theory. A new avenue of research has been on function of circadian genes and whether these are related to breast cancer risk. In particular, a length variant of Per3 (5-VNTR) has been associated with increased risk in young women, and this same 5-VNTR variant has also been found to predict morning diurnal type and shorter sleep duration compared to the 4-VNTR variant. An important question is how an effect of light-at-night (LAN) exposure on breast cancer risk might be modified by polymorphisms and/or epigenetic alterations in the circadian genes, and conversely whether light-at-night exposure (e.g., shift work) can induce deleterious epigenetic changes in these genes.

86 citations

Journal ArticleDOI
TL;DR: This work mostly relies on a sensitivity analysis conducted with the light pollution radiative transfer model, Illumina, which considers different behaviour as a function of the distance from the city centre, along with different zenith viewing angles in the principal plane.
Abstract: Propagation of artificial light at night (ALAN) in the environment is now known to have non negligible consequences on fauna, flora and human health. These consequences depend on light levels and their spectral power distributions, which in turn rely on the efficiency of various physical processes involved in the radiative transfer of this light into the atmosphere and its interactions with the built and natural environment. ALAN can affect the living organisms by direct lighting and indirect lighting (scattered by the sky and clouds and/or reflected by local surfaces). This paper mainly focuses on the behaviour of the indirect light scattered under clear sky conditions. Various interaction processes between anthropogenic light sources and the natural environment are discussed. This work mostly relies on a sensitivity analysis conducted with the light pollution radiative transfer model, Illumina (Aube et al. 2005 Light pollution modelling and detection in a heterogeneous environment: toward a night-time aerosol optical depth retrieval method. In Proc. SPIE 2005, vol. 5890, San Diego, California, USA). More specifically, the impact of (i) the molecular and aerosol scattering and absorption, (ii) the second order of scattering, (iii) the topography and obstacle blocking, (iv) the ground reflectance and (v) the spectrum of light devices and their angular emission functions are examined. This analysis considers different behaviour as a function of the distance from the city centre, along with different zenith viewing angles in the principal plane.

86 citations

Journal ArticleDOI
TL;DR: Positive associations between LAN and BC incidence are suggested, especially among whites, and the consistency of the findings with previous studies suggests that there could be fundamental biological links between exposure to artificial LAN and increased BC incidence.
Abstract: Literature has identified detrimental health effects from the indiscriminate use of artificial nighttime light. We examined the co-distribution of light at night (LAN) and breast cancer (BC) incidence in Georgia, with the goal to contribute to the accumulating evidence that exposure to LAN increases risk of BC. Using Georgia Comprehensive Cancer Registry data (2000–2007), we conducted a case-referent study among 34,053 BC cases and 14,458 lung cancer referents. Individuals with lung cancer were used as referents to control for other cancer risk factors that may be associated with elevated LAN, such as air pollution, and since this cancer type was not previously associated with LAN or circadian rhythm disruption. DMSP-OLS Nighttime Light Time Series satellite images (1992–2007) were used to estimate LAN levels; low (0–20 watts per sterradian cm2), medium (21–41 watts per sterradian cm2), high (>41 watts per sterradian cm2). LAN levels were extracted for each year of exposure prior to case/referent diagnosis in ArcGIS. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models controlling for individual-level year of diagnosis, race, age at diagnosis, tumor grade, stage; and population-level determinants including metropolitan statistical area (MSA) status, births per 1,000 women aged 15–50, percentage of female smokers, MSA population mobility, and percentage of population over 16 in the labor force. We found that overall BC incidence was associated with high LAN exposure (OR = 1.12, 95% CI [1.04, 1.20]). When stratified by race, LAN exposure was associated with increased BC risk among whites (OR = 1.13, 95% CI [1.05, 1.22]), but not among blacks (OR = 1.02, 95% CI [0.82, 1.28]). Our results suggest positive associations between LAN and BC incidence, especially among whites. The consistency of our findings with previous studies suggests that there could be fundamental biological links between exposure to artificial LAN and increased BC incidence, although additional research using exposure metrics at the individual level is required to confirm or refute these findings.

86 citations


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

  • ...Background Increasing urban development and the subsequent need for artificial lighting of roadways, shopping centers, and homes, has diminished the daily dark period [1]....

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References
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Journal ArticleDOI
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