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: 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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References
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TL;DR: Preliminary data support the hypothesis that higher melatonin levels, as measured in first morning urine, are associated with a lower risk of breast cancer.
Abstract: Exposure to light at night suppresses melatonin production, and night-shift work (a surrogate for such exposure) has been associated with an increased risk of breast cancer. However, the association between circulating melatonin levels and breast cancer risk is unclear. In a prospective case-control study nested within the Nurses' Health Study II cohort, we measured the concentration of the major melatonin metabolite, 6-sulphatoxymelatonin (aMT6s), in the first morning urine of 147 women with invasive breast cancer and 291 matched control subjects. In logistic regression models, the relative risk (reported as the odds ratio [OR]) of invasive breast cancer for women in the highest quartile of urinary aMT6s compared with those in the lowest was 0.59 (95% confidence interval [CI] = 0.36 to 0.97). This association was essentially unchanged after adjustment for breast cancer risk factors or plasma sex hormone levels but was slightly weakened when the analysis included 43 case patients with in situ breast cancer and their 85 matched control subjects (OR = 0.70, 95% CI = 0.47 to 1.06). The exclusion of women who had a history of night-shift work left our findings largely unchanged. These prospective data support the hypothesis that higher melatonin levels, as measured in first morning urine, are associated with a lower risk of breast cancer.
184 citations
TL;DR: The relationship among Norwegian nurses educated between 1914 and 1980 is evaluated, finding an association between night work and breast cancer risk among women in accordance with previous studies.
Abstract: Objective Previous studies have suggested an association between breast cancer and night work. We evaluated the relationship among Norwegian nurses. Methods A case–control study, nested within a cohort of 44,835 nurses educated between 1914 and 1980 was performed, based on a registry of all Norwegian nurses. Four controls were individually matched by year of birth to each of 537 breast cancer cases that occurred during the period 1960–1982. The reconstruction of work history and number of years with night work for each nurse was based on information from the nurse registry, and data from three censuses. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for total duration of work as a nurse and parity. All statistical tests were two-sided. Results The adjusted OR of breast cancer among nurses who worked nights for 30 or more years was 2.21 (CI 1.10–4.45) compared with those who did not work nights after graduation from nursing school (ptrend = 0.01). Conclusion Our results are in accordance with previous studies that find an association between night work and breast cancer risk among women.
182 citations
Journal Article•
TL;DR: Investigating the association between an exonic length variation in a circadian gene, Period3 (Per3), and breast cancer risk using blood samples collected from a recently completed breast cancer case-control study in Connecticut found that the variant Per3 genotype was associated with an increased risk of breast cancer among premenopausal women.
Abstract: Circadian disruption has been indicated as a risk factor for breast cancer in recent epidemiologic studies. A novel finding in circadian biology is that genes responsible for circadian rhythm also regulate many other biological pathways, including cell proliferation, cell cycle regulation, and apoptosis. Therefore, mutations in circadian genes could conceivably result in deregulation of these processes and contribute to tumor development, and be markers for susceptibility to human cancer. In this study, we investigated the association between an exonic length variation in a circadian gene, Period3 (Per3), and breast cancer risk using blood samples collected from a recently completed breast cancer case-control study in Connecticut. There were 389 Caucasian cases and 432 Caucasian controls included in our analysis. We found that the variant Per3 genotype (heterozygous + homozygous 5-repeat alleles) was associated with an increased risk of breast cancer among premenopausal women (odds ratio, 1.7; 95% confidence interval, 1.0-3.0). Our finding suggests that the circadian genes might be a novel panel of potential biomarkers for breast cancer and worth further investigation.
176 citations
TL;DR: It is proposed that the use of electrical power accounts, in part, for the higher risks of breast cancer in industrialized societies through generation of electric power and exposure to electromagnetic fields.
Abstract: Breast cancer is the leading cause of cancer death in women in the industrialized world, and the rates of breast cancer incidence are rising. Although risk is high in industrialized societies, it i...
175 citations
TL;DR: This study provides some support for a decreased risk of breast cancer in long sleepers, possibly due to greater overall melatonin production in longer sleepers.
Abstract: Breast cancer incidence has increased during recent decades for reasons that are only partly understood. Prevalence of sleeping difficulties and sleepiness has increased, whereas sleeping duration per night has decreased. We hypothesized that there is an inverse association between sleep duration and breast cancer risk, possibly due to greater overall melatonin production in longer sleepers. This population-based study includes information from women born in Finland before 1958. Sleep duration, other sleep variables, and breast cancer risk factors were assessed by self-administered questionnaires given in 1975 and in 1981. Breast cancer incidence data for 1976 to 1996 was obtained from the Finnish Cancer Registry. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained from Cox proportional hazards models adjusting for potential confounders. Altogether, 242 cases of breast cancer occurred over the study period among the 12,222 women with sleep duration data in 1975. For these women, the HRs for breast cancer in the short (≤6 hours), average (7-8 hours), and long sleep (≥9 hours) duration groups were 0.85 (CI, 0.54-1.34), 1.0 (referent), and 0.69 (CI, 0.45-1.06), respectively. Analysis restricted to the 7,396 women (146 cases) whose sleep duration in 1975 and 1981 were in the same duration group (stable sleepers) yielded HRs of 1.10 (CI, 0.59-2.05), 1.0, and 0.28 (CI, 0.09-0.88), with a decreasing trend (P = 0.03). This study provides some support for a decreased risk of breast cancer in long sleepers.
174 citations