Abstract
Light controls pineal melatonin production and temporally coordinates circadian rhythms of metabolism and physiology in normal and neoplastic tissues. We previously showed that peak circulating nocturnal melatonin levels were 7-fold higher after daytime spectral transmittance of white light through blue-tinted (compared with clear) rodent cages. Here, we tested the hypothesis that daytime blue-light amplification of nocturnal melatonin enhances the inhibition of metabolism, signaling activity, and growth of prostate cancer xenografts. Compared with male nude rats housed in clear cages under a 12:12-h light:dark cycle, rats in blue-tinted cages (with increased transmittance of 462-484 nm and decreased red light greater than 640 nm) evinced over 6-fold higher peak plasma melatonin levels at middark phase (time, 2400), whereas midlight-phase levels (1200) were low (less than 3 pg/mL) in both groups. Circadian rhythms of arterial plasma levels of linoleic acid, glucose, lactic acid, pO2, pCO2, insulin, leptin, and corticosterone were disrupted in rats in blue cages as compared with the corresponding entrained rhythms in clear-caged rats. After implantation with tissue-isolated PC3 human prostate cancer xenografts, tumor latency-to-onset of growth and growth rates were markedly delayed, and tumor cAMP levels, uptake-metabolism of linoleic acid, aerobic glycolysis (Warburg effect), and growth signaling activities were reduced in rats in blue compared with clear cages. These data show that the amplification of nighttime melatonin levels by exposing nude rats to blue light during the daytime significantly reduces human prostate cancer metabolic, signaling, and proliferative activities.
https://pubmed.ncbi.nlm.nih.gov/26678364/
Cancer
Cancer is the term used to describe cells in the body that start uncontrolled cell division. The cells change character due to mutations in their genetic material and will subsequently spread to the surrounding tissue and then spread to other places in the body through the blood. The cancer cells inhibit the growth of the normal cells and, without treatment, cancer eventually leads to death. Today, there are many treatment methods in the medical world and the treatments are getting better all the time.
Description
There are many forms of cancer, and the mystery of cancer is far from solved. But there is a strong suggestion that there is a connection between cancer, light and melatonin.
Cancer and light
If there were no artificial light on earth, we humans would be surrounded by darkness for an average of 12 hours every day.
Experiments conducted at Harvard University have shown that blind people, who always experience darkness, produce melatonin for 9-10 hours a night. Blind people also have a 50% lower risk of developing cancer compared to sighted people.
Due to artificial lighting, most people in the Western world are only exposed to darkness for 7-8 hours a night. This reduces the nocturnal production of melatonin to 6-7 hours.
Many different studies on both animals and humans point to a connection between artificial light and cancer. In an experimental animal experiment, tumours grew rapidly in animals raised in an environment with short nights and high artificial lighting, while tumours stopped growing or grew slowly in animals raised in an environment with long nights and less artificial lighting.
Using artificial lighting reduces the duration of melatonin production and the presence of melatonin in the blood. Studies of primitive societies, which are surrounded by longer periods of darkness, since they do not have artificial lighting, have shown a much lower incidence of cancer. There are of course other variables when comparing modern cultures to primitive cultures, but a growing body of evidence points to a link between the use of artificial lighting and increased health risks.
Melatonin is not the only substance produced in the pineal gland, which is quite complex. It has not yet been finally decided whether these other substances also play a significant role in the fight against cancer. This may be the reason why melatonin tablets do not seem to be as effective in fighting cancer cells as the body's own naturally produced melatonin.
Since it seems unlikely that in the near future we will give up electric lighting, it is especially encouraging to know that in 2002 the discovery was made that not all the light in the visible light spectrum inhibits the production of melatonin. It is the blue light in this light spectrum that causes inhibition of melatonin. You can solve the problem by blocking the blue light. You can use lighting that filters out the blue light for practical use, e.g. for reading, watching TV or when working on a computer. This was first demonstrated at the University of Toronto when subjects simulated night work while wearing special glasses that blocked all blue light. The subjects produced melatonin even though they were in brightly lit environments.
Melatonin and cancer in general
There is much evidence that melatonin has a protective effect in many cancer contexts:
Melatonin strengthens the body's immune system.
Melatonin strengthens the cells' ability to destroy themselves if they have been damaged. A damaged cell can develop into a cancer cell.
As an antioxidant, melatonin helps to protect the body's cells and tissues against free radicals, which are formed when oxygen is converted into energy in the body. The free radicals can damage the cells and contribute to the development of diseases, including cancer.
Melatonin may reduce the harmful effects of radiotherapy and chemotherapy.
Melatonin may reduce the production of oestrogen that some cancers depend on.
Melatonin and breast cancer
A large number of studies have been carried out which demonstrate a remarkable correlation between night work/shift work and various forms of cancer.
The Cancer Society in Denmark, for example, investigated whether there is an increased risk of breast cancer among women who engage in evening and night work.
The study was conducted among Danish women aged 30-54 and showed that the risk of breast cancer increased by up to 40% among women who work in the evening or at night.
This may be because people who do evening or night work produce less melatonin because they are exposed to light at night.
Similar studies are underway among men to investigate whether there is also a connection between evening and night work and prostate cancer.
Cancer and sleep glasses
If you work in the evening or at night and as a result need to sleep during the day, it may be a good idea to use sleep glasses 1-2 hours before you go to sleep. The sleep glasses can help to extend the duration of melatonin production, so that you get the normal and optimal 9-10 hours of melatonin production per day. In addition, it is crucial that you sleep in an completely dark room.
Trial
A crucial experiment was conducted by the highly experienced researchers Dr. George Brainard, who is a professor of neurology and Dr. David Blask, who is a researcher. They examined blood samples taken from women under three different conditions: during the day, when melatonin was not present in the blood - in the dark at night, when melatonin was present in the blood - and during the night, when the women had been exposed to several hours of artificial light. No melatonin was present in the blood of the last group of women. In another phase of the experiment, this blood (without melatonin) was injected into human mammary tumours that grew in laboratory rats. This resulted in the tumours growing rapidly. Injecting blood with melatonin resulted in the tumours growing slowly, and some tumours did not grow at all. Dr. Blask commented that blood containing melatonin "put tumours to sleep".
Research regarding cancer
Daytime Blue Light Enhances the Nighttime Circadian Melatonin Inhibition of Human Prostate Cancer Growth
Comp Med. 2015 Dec;65(6):473-85.Robert T Dauchy, Aaron E Hoffman, Melissa A Wren-Dail, John P Hanifin, Benjamin Warfield, George C Brainard, Shulin Xiang, Lin Yuan, Steven M Hill, Victoria P Belancio, Erin M Dauchy, Kara Smith, David E BlaskPMID: 26678364 / PMCID: PMC4681241
We tested the hypothesis that daytime exposure to blue light enhances nocturnal melatonin production and increases the inhibition of the metabolism, signalling activity and growth of prostate cancer xenografts. These...
Daytime Blue Light Enhances the Nighttime Circadian Melatonin Inhibition of Human Prostate Cancer Growth
We tested the hypothesis that daytime exposure to blue light enhances nocturnal melatonin production and increases the inhibition of the metabolism, signalling activity and growth of prostate cancer xenografts. These data show that the enhancement of nocturnal melatonin levels by exposing nude rats to daytime blue light significantly reduces the metabolic, signalling and proliferative activities of human prostate cancer.
Daytime Blue Light Enhances the Nighttime Circadian Melatonin Inhibition of Human Prostate Cancer Growth
Comp Med. 2015 Dec;65(6):473-85.
PMID: 26678364 / PMCID: PMC4681241
Melatonin: an inhibitor of breast cancer
Endocr Relat Cancer. 2015 Jun;22(3):R183-204. doi: 10.1530/ERC-15-0030. Epub 2015 Apr 15.Steven M Hill, Victoria P Belancio, Robert T Dauchy, Shulin Xiang, Samantha Brimer, Lulu Mao, Adam Hauch, Peter W Lundberg, Whitney Summers, Lin Yuan, Tripp Frasch, David E BlaskPMID: 25876649 / PMCID: PMC4457700 / DOI: 10.1530/ERC-15-0030
The anti-cancer effects of the circadian melatonin signal in human breast cancer cell lines and xenografts largely involve MT1 receptor-mediated mechanisms. Studies have shown that melatonin promotes genomic stability by...
Melatonin: an inhibitor of breast cancer
The anti-cancer effects of the circadian melatonin signal in human breast cancer cell lines and xenografts largely involve MT1 receptor-mediated mechanisms. Studies have shown that melatonin promotes genomic stability by inhibiting the expression of LINE-1 retrotransposons. Finally, research in animal and human models has indicated that light at night disrupts the production of melatonin and promotes the growth, metabolism and signalling of human breast cancer and drives breast tumours to endocrine and chemotherapy resistance. These data provide the strongest understanding and support of the mechanisms supporting the epidemiologic demonstration of increased breast cancer risk in night shift workers and other individuals increasingly exposed to light at night.
Melatonin: an inhibitor of breast cancer
Endocr Relat Cancer. 2015 Jun;22(3):R183-204. doi: 10.1530/ERC-15-0030. Epub 2015 Apr 15.
PMID: 25876649 / PMCID: PMC4457700 / DOI: 10.1530/ERC-15-0030
Abstract
The present review discusses recent work on melatonin-mediated circadian regulation, the metabolic and molecular signaling mechanisms that are involved in human breast cancer growth, and the associated consequences of circadian disruption by exposure to light at night (LEN). The anti-cancer actions of the circadian melatonin signal in human breast cancer cell lines and xenografts heavily involve MT1 receptor-mediated mechanisms. In estrogen receptor alpha (ERα)-positive human breast cancer, melatonin suppresses ERα mRNA expression and ERα transcriptional activity via the MT1 receptor. Melatonin also regulates the transactivation of other members of the nuclear receptor superfamily, estrogen-metabolizing enzymes, and the expression of core clock and clock-related genes. Furthermore, melatonin also suppresses tumor aerobic metabolism (the Warburg effect) and, subsequently, cell-signaling pathways critical to cell proliferation, cell survival, metastasis, and drug resistance. Melatonin demonstrates both cytostatic and cytotoxic activity in breast cancer cells that appears to be cell type-specific. Melatonin also possesses anti-invasive/anti-metastatic actions that involve multiple pathways, including inhibition of p38 MAPK and repression of epithelial-mesenchymal transition (EMT). Studies have demonstrated that melatonin promotes genomic stability by inhibiting the expression of LINE-1 retrotransposons. Finally, research in animal and human models has indicated that LEN-induced disruption of the circadian nocturnal melatonin signal promotes the growth, metabolism, and signaling of human breast cancer and drives breast tumors to endocrine and chemotherapeutic resistance. These data provide the strongest understanding and support of the mechanisms that underpin the epidemiologic demonstration of elevated breast cancer risk in night-shift workers and other individuals who are increasingly exposed to LEN.
https://pubmed.ncbi.nlm.nih.gov/25876649/
The present review discusses recent work on melatonin-mediated circadian regulation, the metabolic and molecular signaling mechanisms that are involved in human breast cancer growth, and the associated consequences of circadian disruption by exposure to light at night (LEN). The anti-cancer actions of the circadian melatonin signal in human breast cancer cell lines and xenografts heavily involve MT1 receptor-mediated mechanisms. In estrogen receptor alpha (ERα)-positive human breast cancer, melatonin suppresses ERα mRNA expression and ERα transcriptional activity via the MT1 receptor. Melatonin also regulates the transactivation of other members of the nuclear receptor superfamily, estrogen-metabolizing enzymes, and the expression of core clock and clock-related genes. Furthermore, melatonin also suppresses tumor aerobic metabolism (the Warburg effect) and, subsequently, cell-signaling pathways critical to cell proliferation, cell survival, metastasis, and drug resistance. Melatonin demonstrates both cytostatic and cytotoxic activity in breast cancer cells that appears to be cell type-specific. Melatonin also possesses anti-invasive/anti-metastatic actions that involve multiple pathways, including inhibition of p38 MAPK and repression of epithelial-mesenchymal transition (EMT). Studies have demonstrated that melatonin promotes genomic stability by inhibiting the expression of LINE-1 retrotransposons. Finally, research in animal and human models has indicated that LEN-induced disruption of the circadian nocturnal melatonin signal promotes the growth, metabolism, and signaling of human breast cancer and drives breast tumors to endocrine and chemotherapeutic resistance. These data provide the strongest understanding and support of the mechanisms that underpin the epidemiologic demonstration of elevated breast cancer risk in night-shift workers and other individuals who are increasingly exposed to LEN.
https://pubmed.ncbi.nlm.nih.gov/25876649/
Breast cancer and circadian disruption from electric lighting in the modern world
CA Cancer J Clin. 2014 May-Jun;64(3):207-18. doi: 10.3322/caac.21218. Epub 2013 Dec 24.Richard G Stevens, George C Brainard, David E Blask, Steven W Lockley, Mario E MottaPMID: 24604162 / PMCID: PMC4038658 / DOI: 10.3322/caac.21218
Breast cancer is the leading cause of cancer death among women worldwide, and there is only a limited explanation as to why. It has only recently become clear that this...
Breast cancer and circadian disruption from electric lighting in the modern world
Breast cancer is the leading cause of cancer death among women worldwide, and there is only a limited explanation as to why. It has only recently become clear that this evolutionarily new and thus unnatural exposure can disrupt the human circadian rhythm, three prominent features of which are melatonin production, sleep and the circadian rhythm. An innovative experiment has shown that light at night significantly increases the growth of human breast cancer xenografts in rats. In humans, the theory that exposure to light at night increases the risk of breast cancer leads to specific predictions that are being tested epidemiologically: evidence has accumulated on risk in shift workers, risk in blind women, and the impact of sleep duration on risk. If electric light at night explains part of the breast cancer burden, then there are practical interventions that can be implemented, including more selective use of light and adopting the latest advances in lighting technology and applications.
Breast cancer and circadian disruption from electric lighting in the modern world
CA Cancer J Clin. 2014 May-Jun;64(3):207-18. doi: 10.3322/caac.21218. Epub 2013 Dec 24.
PMID: 24604162 / PMCID: PMC4038658 / DOI: 10.3322/caac.21218
Abstract
Breast cancer is the leading cause of cancer death among women worldwide, and there is only a limited explanation of why. Risk is highest in the most industrialized countries but also is rising rapidly in the developing world. Known risk factors account for only a portion of the incidence in the high-risk populations, and there has been considerable speculation and many false leads on other possibly major determinants of risk, such as dietary fat. A hallmark of industrialization is the increasing use of electricity to light the night, both within the home and without. It has only recently become clear that this evolutionarily new and, thereby, unnatural exposure can disrupt human circadian rhythmicity, of which three salient features are melatonin production, sleep, and the circadian clock. A convergence of research in cells, rodents, and humans suggests that the health consequences of circadian disruption may be substantial. An innovative experimental model has shown that light at night markedly increases the growth of human breast cancer xenografts in rats. In humans, the theory that light exposure at night increases breast cancer risk leads to specific predictions that are being tested epidemiologically: evidence has accumulated on risk in shift workers, risk in blind women, and the impact of sleep duration on risk. If electric light at night does explain a portion of the breast cancer burden, then there are practical interventions that can be implemented, including more selective use of light and the adoption of recent advances in lighting technology and application.
https://pubmed.ncbi.nlm.nih.gov/24604162/
Breast cancer is the leading cause of cancer death among women worldwide, and there is only a limited explanation of why. Risk is highest in the most industrialized countries but also is rising rapidly in the developing world. Known risk factors account for only a portion of the incidence in the high-risk populations, and there has been considerable speculation and many false leads on other possibly major determinants of risk, such as dietary fat. A hallmark of industrialization is the increasing use of electricity to light the night, both within the home and without. It has only recently become clear that this evolutionarily new and, thereby, unnatural exposure can disrupt human circadian rhythmicity, of which three salient features are melatonin production, sleep, and the circadian clock. A convergence of research in cells, rodents, and humans suggests that the health consequences of circadian disruption may be substantial. An innovative experimental model has shown that light at night markedly increases the growth of human breast cancer xenografts in rats. In humans, the theory that light exposure at night increases breast cancer risk leads to specific predictions that are being tested epidemiologically: evidence has accumulated on risk in shift workers, risk in blind women, and the impact of sleep duration on risk. If electric light at night does explain a portion of the breast cancer burden, then there are practical interventions that can be implemented, including more selective use of light and the adoption of recent advances in lighting technology and application.
https://pubmed.ncbi.nlm.nih.gov/24604162/
Hypotheses for mechanisms linking shiftwork and cancer
Med Hypotheses. 2011 Sep;77(3):430-6. doi: 10.1016/j.mehy.2011.06.002. Epub 2011 Jul 1.L Fritschi, D C Glass, J S Heyworth, K Aronson, J Girschik, T Boyle, A Grundy, T C ErrenPMID: 21723672 / DOI: 10.1016/j.mehy.2011.06.002
Several studies have recently been carried out showing that a potential cancer risk may be associated with night work and shift work. We suggest four additional mechanisms that should be...
Hypotheses for mechanisms linking shiftwork and cancer
Several studies have recently been carried out showing that a potential cancer risk may be associated with night work and shift work. We suggest four additional mechanisms that should be considered for a comprehensive investigation of these potential possibilities. These are: phase shifts, sleep disturbances, lifestyle factors (such as poor-quality diets, less physical activity and higher BMI) and vitamin D deficiency. It is necessary to consider these four mechanisms in order to design effective preventive strategies for use in the workplace. In developed countries, approx. 20% of the population engage in shift work.
Hypotheses for mechanisms linking shiftwork and cancer
Med Hypotheses. 2011 Sep;77(3):430-6. doi: 10.1016/j.mehy.2011.06.002. Epub 2011 Jul 1.
PMID: 21723672 / DOI: 10.1016/j.mehy.2011.06.002
Abstract
Shift work has been associated with various adverse health outcomes. In particular, there has been a recent flourish in investigating potential cancer risk associated with working night shifts and other shift schedules. Epidemiologic studies have revealed generally weak associations due to several methodological challenges such as lack of standard classifications of shift or night work. The field also has been hindered by a lack of clarity about the possible mechanisms by which shiftwork could have an effect on cancer risk. One possible mechanism is reduced production of melatonin caused by exposure to light at night. Although there is a growing body of evidence that provides some support for this mechanism, several other mechanisms also make sense from a biological point of view. Further, the relatively weak magnitude of the associations between light at night and melatonin level suggests that multiple factors may be operating along the pathway between shift work and adverse health consequences (including cancer risk). Here we propose four additional mechanisms that should be considered for a comprehensive investigation of these potential pathways. These are: phase shift; sleep disruption; lifestyle factors (such as poor quality diets, less physical activity and higher BMI); and lower vitamin D. Consideration of all these mechanisms is necessary in order to design effective preventative workplace strategies. In developed countries, approximately 20% of the population undertake shiftwork and, while we are unlikely to be able to eliminate shiftwork from current work practices, there are aspects of shiftwork that can be modified and there may be facets of individual susceptibility that we may be able to identify and target for prevention.
https://pubmed.ncbi.nlm.nih.gov/21723672/
Shift work has been associated with various adverse health outcomes. In particular, there has been a recent flourish in investigating potential cancer risk associated with working night shifts and other shift schedules. Epidemiologic studies have revealed generally weak associations due to several methodological challenges such as lack of standard classifications of shift or night work. The field also has been hindered by a lack of clarity about the possible mechanisms by which shiftwork could have an effect on cancer risk. One possible mechanism is reduced production of melatonin caused by exposure to light at night. Although there is a growing body of evidence that provides some support for this mechanism, several other mechanisms also make sense from a biological point of view. Further, the relatively weak magnitude of the associations between light at night and melatonin level suggests that multiple factors may be operating along the pathway between shift work and adverse health consequences (including cancer risk). Here we propose four additional mechanisms that should be considered for a comprehensive investigation of these potential pathways. These are: phase shift; sleep disruption; lifestyle factors (such as poor quality diets, less physical activity and higher BMI); and lower vitamin D. Consideration of all these mechanisms is necessary in order to design effective preventative workplace strategies. In developed countries, approximately 20% of the population undertake shiftwork and, while we are unlikely to be able to eliminate shiftwork from current work practices, there are aspects of shiftwork that can be modified and there may be facets of individual susceptibility that we may be able to identify and target for prevention.
https://pubmed.ncbi.nlm.nih.gov/21723672/
Total visual blindness is protective against breast cancer
Cancer Causes Control. 2009 Nov;20(9):1753-6. doi: 10.1007/s10552-009-9405-0. Epub 2009 Aug 1.Erin E Flynn-Evans, Richard G Stevens, Homayoun Tabandeh, Eva S Schernhammer, Steven W LockleyPMID: 19649715 / DOI: 10.1007/s10552-009-9405-0
Although the amount of data is sparse and based on small studies with limited ability to control for known breast cancer risk factors, a lower risk of breast cancer in...
Total visual blindness is protective against breast cancer
Although the amount of data is sparse and based on small studies with limited ability to control for known breast cancer risk factors, a lower risk of breast cancer in blind women compared to sighted women is supported. Mechanisms influenced by ocular light perception, such as melatonin or circadian rhythm synchronisation, are thought to account for this lower risk. To evaluate whether blind women not exposed to light have a lower incidence of breast cancer compared with blind women exposed to light, we studied a cohort of 1,392 blind women living in North America (66 cases of breast cancer). Blind women who are not exposed to light appear to have a lower risk of breast cancer compared to blind women who are exposed to light.
Total visual blindness is protective against breast cancer
Cancer Causes Control. 2009 Nov;20(9):1753-6. doi: 10.1007/s10552-009-9405-0. Epub 2009 Aug 1.
PMID: 19649715 / DOI: 10.1007/s10552-009-9405-0
Abstract
Objective: Observational data, though sparse and based on small studies with limited ability to control for known breast cancer risk factors, support a lower risk of breast cancer in blind women compared to sighted women. Mechanisms influenced by ocular light perception, such as melatonin or circadian synchronization, are thought to account for this lower risk.
Methods: To evaluate whether blind women with no perception of light (NPL) have a lower prevalence of breast cancer compared to blind women with light perception (LP), we surveyed a cohort of 1,392 blind women living in North America (66 breast cancer cases).
Results: In multivariate-logistic regression models controlling for breast cancer risk factors, women with NPL had a significantly lower prevalence of breast cancer than women with LP (odds ratio, 0.43; 95% confidence interval, 0.21-0.85). We observed little difference in these associations when restricting to postmenopausal women, non-shift workers or when excluding women diagnosed with breast cancer within 2 or 4 years of onset of blindness. Blind women with NPL appear to have a lower risk of breast cancer, compared to blind women with LP. More research is needed to elucidate the impact of LP on circadian coordination and melatonin production in the blind and how these factors may relate to breast cancer risk.
https://pubmed.ncbi.nlm.nih.gov/19649715/
Objective: Observational data, though sparse and based on small studies with limited ability to control for known breast cancer risk factors, support a lower risk of breast cancer in blind women compared to sighted women. Mechanisms influenced by ocular light perception, such as melatonin or circadian synchronization, are thought to account for this lower risk.
Methods: To evaluate whether blind women with no perception of light (NPL) have a lower prevalence of breast cancer compared to blind women with light perception (LP), we surveyed a cohort of 1,392 blind women living in North America (66 breast cancer cases).
Results: In multivariate-logistic regression models controlling for breast cancer risk factors, women with NPL had a significantly lower prevalence of breast cancer than women with LP (odds ratio, 0.43; 95% confidence interval, 0.21-0.85). We observed little difference in these associations when restricting to postmenopausal women, non-shift workers or when excluding women diagnosed with breast cancer within 2 or 4 years of onset of blindness. Blind women with NPL appear to have a lower risk of breast cancer, compared to blind women with LP. More research is needed to elucidate the impact of LP on circadian coordination and melatonin production in the blind and how these factors may relate to breast cancer risk.
https://pubmed.ncbi.nlm.nih.gov/19649715/
Melatonin, sleep disturbance and cancer risk
Sleep Med Rev. 2009 Aug;13(4):257-64. doi: 10.1016/j.smrv.2008.07.007. Epub 2008 Dec 17.David E BlaskPMID: 19095474 / DOI: 10.1016/j.smrv.2008.07.007
The pineal hormone melatonin is involved in regulating the circadian rhythm and makes it easier to fall asleep. It can also inhibit cancer development and growth and improve immune function....
Melatonin, sleep disturbance and cancer risk
The pineal hormone melatonin is involved in regulating the circadian rhythm and makes it easier to fall asleep. It can also inhibit cancer development and growth and improve immune function. Individuals who are exposed to light at night on a regular basis, such as shift workers, experience disturbances to their biological rhythms (i.e., circadian rhythms), including circadian phase shifts, nocturnal suppression of melatonin, and sleep disturbances. Some studies suggest that a shortened duration of sleep at night is associated with a higher risk of developing breast cancer. The mutual reinforcement of interacting circadian rhythms of melatonin production, sleep/wake cycle, and immune function may indicate a new role for undisturbed, high-quality sleep, and perhaps more importantly, uninterrupted darkness, as a previously unappreciated endogenous mechanism for cancer prevention.
Melatonin, sleep disturbance and cancer risk
Sleep Med Rev. 2009 Aug;13(4):257-64. doi: 10.1016/j.smrv.2008.07.007. Epub 2008 Dec 17.
PMID: 19095474 / DOI: 10.1016/j.smrv.2008.07.007
Abstract
The pineal hormone melatonin is involved in the circadian regulation and facilitation of sleep, the inhibition of cancer development and growth, and the enhancement of immune function. Individuals, such as night shift workers, who are exposed to light at night on a regular basis experience biological rhythm (i.e., circadian) disruption including circadian phase shifts, nocturnal melatonin suppression, and sleep disturbances. Additionally, these individuals are not only immune suppressed, but they are also at an increased risk of developing a number of different types of cancer. There is a reciprocal interaction and regulation between sleep and the immune system quite independent of melatonin. Sleep disturbances can lead to immune suppression and a shift to the predominance in cancer-stimulatory cytokines. Some studies suggest that a shortened duration of nocturnal sleep is associated with a higher risk of breast cancer development. The relative individual contributions of sleep disturbance, circadian disruption due to light at night exposure, and related impairments of melatonin production and immune function to the initiation and promotion of cancer in high-risk individuals such as night shift workers are unknown. The mutual reinforcement of interacting circadian rhythms of melatonin production, the sleep/wake cycle and immune function may indicate a new role for undisturbed, high quality sleep, and perhaps even more importantly, uninterrupted darkness, as a previously unappreciated endogenous mechanism of cancer prevention.
https://pubmed.ncbi.nlm.nih.gov/19095474/
The pineal hormone melatonin is involved in the circadian regulation and facilitation of sleep, the inhibition of cancer development and growth, and the enhancement of immune function. Individuals, such as night shift workers, who are exposed to light at night on a regular basis experience biological rhythm (i.e., circadian) disruption including circadian phase shifts, nocturnal melatonin suppression, and sleep disturbances. Additionally, these individuals are not only immune suppressed, but they are also at an increased risk of developing a number of different types of cancer. There is a reciprocal interaction and regulation between sleep and the immune system quite independent of melatonin. Sleep disturbances can lead to immune suppression and a shift to the predominance in cancer-stimulatory cytokines. Some studies suggest that a shortened duration of nocturnal sleep is associated with a higher risk of breast cancer development. The relative individual contributions of sleep disturbance, circadian disruption due to light at night exposure, and related impairments of melatonin production and immune function to the initiation and promotion of cancer in high-risk individuals such as night shift workers are unknown. The mutual reinforcement of interacting circadian rhythms of melatonin production, the sleep/wake cycle and immune function may indicate a new role for undisturbed, high quality sleep, and perhaps even more importantly, uninterrupted darkness, as a previously unappreciated endogenous mechanism of cancer prevention.
https://pubmed.ncbi.nlm.nih.gov/19095474/
Light at night, chronodisruption, melatonin suppression, and cancer risk: a review
Crit Rev Oncog. 2007 Dec;13(4):303-28. doi: 10.1615/critrevoncog.v13.i4.30.Russel J Reiter, Dun-Xian Tan, Ahmet Korkmaz, Thomas C Erren, Claus Piekarski, Hiroshi Tamura, Lucien C ManchesterPMID: 18540832 / DOI: 10.1615/critrevoncog.v13.i4.30
Light at night has two major physiological effects, namely it disrupts circadian rhythms and suppresses the production of melatonin in the pineal gland. Both human epidemiological and experimental studies on...
Light at night, chronodisruption, melatonin suppression, and cancer risk: a review
Light at night has two major physiological effects, namely it disrupts circadian rhythms and suppresses the production of melatonin in the pineal gland. Both human epidemiological and experimental studies on animals have documented that a potential negative consequence of disrupting the brain's internal clock and dampening melatonin production at night is carcinogenic and growth-promoting. In epidemiologic studies, the incidence of each of the following cancers has been reported to be increased in people who routinely work at night or whose circadian rhythm is disrupted for other reasons (e.g., due to jet lag): breast, prostate, endometrial, and colorectal.
Light at night, chronodisruption, melatonin suppression, and cancer risk: a review
Crit Rev Oncog. 2007 Dec;13(4):303-28. doi: 10.1615/critrevoncog.v13.i4.30.
PMID: 18540832 / DOI: 10.1615/critrevoncog.v13.i4.30
Abstract
Light exposure during the night is becoming progressively more common throughout the world, particularly in areas where electricity is commonly used. Also, the availability of artificial light has allowed humans to work or recreate throughout the 24-hour day. Based on photographs taken of the Earth from outer space, it is also apparent that true darkness is disappearing. For years it was assumed that polluting the daily dark period with light was inconsequential in terms of animal/human physiology. That assumption, however, has proven incorrect. Light at night has two major physiological actions, i.e., it disrupts circadian rhythms and suppresses the production of melatonin by the pineal gland. Moreover, both these changes are light intensity and wavelength dependent. Both human epidemiological and experimental studies on animals have documented that a potential negative consequence of chronodisruption and nocturnal melatonin inhibition is cancer initiation and growth. In epidemiological studies, the frequency of each of the following cancers has been reportedly increased in individuals who routinely work at night or whose circadian rhythms are disrupted for other reasons (e.g., due to jet lag): breast, prostate, endometrial, and colorectal. Likewise, in experimental animals, cancer growth is exaggerated when the animals are repeatedly phase advanced (as occurs during easterly flights) or exposed to light at night. A variety of mechanisms have been examined to explain how the suppression of melatonin exaggerates cancer risk. Mechanistically, how chronodisruption (without a consideration of melatonin suppression) would enhance cancer frequency is less clear. In addition to cancer, there may be other diseases that result from the chronic suppression of melatonin by light at night.
https://pubmed.ncbi.nlm.nih.gov/18540832/
Light exposure during the night is becoming progressively more common throughout the world, particularly in areas where electricity is commonly used. Also, the availability of artificial light has allowed humans to work or recreate throughout the 24-hour day. Based on photographs taken of the Earth from outer space, it is also apparent that true darkness is disappearing. For years it was assumed that polluting the daily dark period with light was inconsequential in terms of animal/human physiology. That assumption, however, has proven incorrect. Light at night has two major physiological actions, i.e., it disrupts circadian rhythms and suppresses the production of melatonin by the pineal gland. Moreover, both these changes are light intensity and wavelength dependent. Both human epidemiological and experimental studies on animals have documented that a potential negative consequence of chronodisruption and nocturnal melatonin inhibition is cancer initiation and growth. In epidemiological studies, the frequency of each of the following cancers has been reportedly increased in individuals who routinely work at night or whose circadian rhythms are disrupted for other reasons (e.g., due to jet lag): breast, prostate, endometrial, and colorectal. Likewise, in experimental animals, cancer growth is exaggerated when the animals are repeatedly phase advanced (as occurs during easterly flights) or exposed to light at night. A variety of mechanisms have been examined to explain how the suppression of melatonin exaggerates cancer risk. Mechanistically, how chronodisruption (without a consideration of melatonin suppression) would enhance cancer frequency is less clear. In addition to cancer, there may be other diseases that result from the chronic suppression of melatonin by light at night.
https://pubmed.ncbi.nlm.nih.gov/18540832/
Melatonin-depleted blood from premenopausal women exposed to light at night stimulates growth of human breast cancer xenografts in nude rats
Cancer Res. 2005 Dec 1;65(23):11174-84. doi: 10.1158/0008-5472.CAN-05-1945.David E Blask, George C Brainard, Robert T Dauchy, John P Hanifin, Leslie K Davidson, Jean A Krause, Leonard A Sauer, Moises A Rivera-Bermudez, Margarita L Dubocovich, Samar A Jasser, Darin T Lynch, Mark D Rollag, Frederick ZalatanPMID: 16322268 / DOI: 10.1158/0008-5472.CAN-05-1945
It has been postulated that the increased risk of breast cancer in female shift workers is due to the attenuation of melatonin production by exposure to light at night. These...
Melatonin-depleted blood from premenopausal women exposed to light at night stimulates growth of human breast cancer xenografts in nude rats
It has been postulated that the increased risk of breast cancer in female shift workers is due to the attenuation of melatonin production by exposure to light at night. These results are the first to show that the tumour growth response to light exposure in the dark is intensity-dependent and that the human nocturnal circadian melatonin signal not only inhibits human breast cancer growth but that this effect is abolished by short-term eye exposure to bright white light at night.
Melatonin-depleted blood from premenopausal women exposed to light at night stimulates growth of human breast cancer xenografts in nude rats
Cancer Res. 2005 Dec 1;65(23):11174-84. doi: 10.1158/0008-5472.CAN-05-1945.
PMID: 16322268 / DOI: 10.1158/0008-5472.CAN-05-1945
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 microW/cm2) 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 microW/cm2 (i.e., 2,800 lx). Compared with tumors perfused with daytime-collected 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.
https://pubmed.ncbi.nlm.nih.gov/16322268/
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 microW/cm2) 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 microW/cm2 (i.e., 2,800 lx). Compared with tumors perfused with daytime-collected 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.
https://pubmed.ncbi.nlm.nih.gov/16322268/
Night work and breast cancer risk: a systematic review and meta-analysis
Eur J Cancer. 2005 Sep;41(13):2023-32. doi: 10.1016/j.ejca.2005.05.010.Sarah P Megdal, Candyce H Kroenke, Francine Laden, Eero Pukkala, Eva S SchernhammerPMID: 16084719 / DOI: 10.1016/j.ejca.2005.05.010
The association between occupations involving night shift work (a surrogate for exposure to light at night with subsequent attenuation of melatonin production) and breast cancer risk is uncertain. We therefore...
Night work and breast cancer risk: a systematic review and meta-analysis
The association between occupations involving night shift work (a surrogate for exposure to light at night with subsequent attenuation of melatonin production) and breast cancer risk is uncertain. We therefore conducted a systematic review and meta-analysis of observational studies to assess the effects of night work on the risk of breast cancer. Studies of night shift work and the risk of breast cancer show an overall increased risk of breast cancer among women.
Night work and breast cancer risk: a systematic review and meta-analysis
Eur J Cancer. 2005 Sep;41(13):2023-32. doi: 10.1016/j.ejca.2005.05.010.
PMID: 16084719 / DOI: 10.1016/j.ejca.2005.05.010
Abstract
The association between occupations that involve night shift work (a surrogate for exposure to light at night with subsequent melatonin suppression) and breast cancer risk is uncertain. We therefore conducted a systematic review and meta-analysis of observational studies to assess the effects of night work on breast cancer risk. Data sources were MEDLINE from January 1960 to January 2005, experts in the field, bibliographies, and abstracts. Search terms included night work terms, flight personnel terms, cancer terms, and risk terms. Independent data extraction by two authors using standardised forms was performed. The method of DerSimonian and Laird was used to derive combined estimates and Egger's; and Begg and Mazumdar's tests for publication bias were conducted. Based on 13 studies, including seven studies of airline cabin crew and six studies of other night shift workers, the aggregate estimate for all studies combined was 1.48 (95% CI, 1.36-1.61), with a similar significant elevation of breast cancer risk among female airline cabin crew (standardised incidence ratio (SIR), 1.44; 95% CI, 1.26-1.65), and female night workers (relative risk (RR), 1.51; 95% CI, 1.36-1.68) separately. We found some evidence suggesting confounding due to incomplete adjustment for breast cancer risk factors, with smaller effects in the studies that more completely adjusted for reproductive history and other confounding factors. Egger's and Begg and Mazumdar's tests for publication bias showed no significant asymmetry (P>0.05). Studies on night shift work and breast cancer risk collectively show an increased breast cancer risk among women. Publication bias is unlikely to have influenced the results.
https://pubmed.ncbi.nlm.nih.gov/16084719/
The association between occupations that involve night shift work (a surrogate for exposure to light at night with subsequent melatonin suppression) and breast cancer risk is uncertain. We therefore conducted a systematic review and meta-analysis of observational studies to assess the effects of night work on breast cancer risk. Data sources were MEDLINE from January 1960 to January 2005, experts in the field, bibliographies, and abstracts. Search terms included night work terms, flight personnel terms, cancer terms, and risk terms. Independent data extraction by two authors using standardised forms was performed. The method of DerSimonian and Laird was used to derive combined estimates and Egger's; and Begg and Mazumdar's tests for publication bias were conducted. Based on 13 studies, including seven studies of airline cabin crew and six studies of other night shift workers, the aggregate estimate for all studies combined was 1.48 (95% CI, 1.36-1.61), with a similar significant elevation of breast cancer risk among female airline cabin crew (standardised incidence ratio (SIR), 1.44; 95% CI, 1.26-1.65), and female night workers (relative risk (RR), 1.51; 95% CI, 1.36-1.68) separately. We found some evidence suggesting confounding due to incomplete adjustment for breast cancer risk factors, with smaller effects in the studies that more completely adjusted for reproductive history and other confounding factors. Egger's and Begg and Mazumdar's tests for publication bias showed no significant asymmetry (P>0.05). Studies on night shift work and breast cancer risk collectively show an increased breast cancer risk among women. Publication bias is unlikely to have influenced the results.
https://pubmed.ncbi.nlm.nih.gov/16084719/
Urinary melatonin levels and breast cancer risk
J Natl Cancer Inst. 2005 Jul 20;97(14):1084-7. doi: 10.1093/jnci/dji190.Eva S Schernhammer, Susan E HankinsonPMID: 16030307 / DOI: 10.1093/jnci/dji190
Exposure to light at night dampens the production of melatonin, and night shift work (a surrogate for such exposure) has been associated with an increased risk of breast cancer. In...
Urinary melatonin levels and breast cancer risk
Exposure to light at night dampens the production of melatonin, and night shift work (a surrogate for such exposure) has been associated with an increased risk of breast cancer. In a prospective case-control study embedded in the Nurses' Health Study II cohort trial, 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 odds ratio [OR]) of invasive breast cancer for women in the highest quartile of urinary aMT6 compared with those in the lowest was 0.59 (95% confidence interval [CI] = 0.36 to 0.97). These prospective data support the hypothesis that higher melatonin levels, measured in the first morning urine, are associated with a lower risk of breast cancer.
Urinary melatonin levels and breast cancer risk
J Natl Cancer Inst. 2005 Jul 20;97(14):1084-7. doi: 10.1093/jnci/dji190.
PMID: 16030307 / DOI: 10.1093/jnci/dji190
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.
https://pubmed.ncbi.nlm.nih.gov/16030307/
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.
https://pubmed.ncbi.nlm.nih.gov/16030307/
Night Shift Work, Light at Night, and Risk of Breast Cancer
JNCI: Journal of the National Cancer Institute, Volume 93, Issue 20, 17 October 2001, Pages 1557-1562Scott Davis, Dana K. Mirick, Richard G. StevensPDMI:0
Exposure to light at night can increase the risk of breast cancer by suppressing the normal nocturnal production of melatonin in the pineal gland, which in turn can increase the...
Night Shift Work, Light at Night, and Risk of Breast Cancer
Exposure to light at night can increase the risk of breast cancer by suppressing the normal nocturnal production of melatonin in the pineal gland, which in turn can increase the release of oestrogen from the ovaries. This study investigated whether such exposure is associated with an increased risk of breast cancer in women. The risk did not increase with interrupted sleep accompanied by turning on a light. There was an indication of increased risk among subjects with the most lit bedrooms. Late-night-to-morning shift work was associated with an increased risk of breast cancer (OR = 1.6; 95% CI = 1.0 to 2.5), with a trend toward increased risk with each year and with more hours per week of shift work from late evening to morning (P = 0.02, Wald chi-square test). Conclusion: The results of this study provide evidence that indicators of exposure to light at night may be associated with the risk of developing breast cancer.
Night Shift Work, Light at Night, and Risk of Breast Cancer
JNCI: Journal of the National Cancer Institute, Volume 93, Issue 20, 17 October 2001, Pages 1557-1562
PDMI:0
Abstract
Background: Exposure to light at night may increase the risk of breast cancer by suppressing the normal nocturnal production of melatonin by the pineal gland, which, in turn, could increase the release of estrogen by the ovaries. This study investigated whether such exposure is associated with an increased risk of breast cancer in women.
Methods: Case patients (n=813), aged 20-74 years, were disgnosed from November 1992 through March 1995; control subjects (n=793) were identified by random-digit dialing and were frequency matched according to 5-year age group. An in-person interview was used to gather information on sleep habits and bedroom lighting environment in the 10 years before diagnosis and lifetime occupational history. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of conditional logistic regression, with adjustment for other potential risk factors.
Result: Breast cancer risk was increased among subjects who frequently did not sleep during the period of the night when melatonin levels are typically at their highest (OR = 1.14 for each night per week; 95% CI = 1.01 to 1.28). Risk did not increase with interrupted sleep accompanied by turning on a light. There was an indication of increased risk among subjects with the brightest bedrooms. Graveyard shiftwork was associated with increased breast cancer risk (OR = 1.6; 95% CI = 1.0 to 2.5), with a trend of increased risk with increasing years and with more hours per week of graveyard shiftwork (P = .02, Wald chi-squared test).
Conclusion: The results of this study provide evidence that indicators of exposure to light at night may be associated with the risk of developing breast cancer.
https://pubmed.ncbi.nlm.nih.gov/11604479/
Background: Exposure to light at night may increase the risk of breast cancer by suppressing the normal nocturnal production of melatonin by the pineal gland, which, in turn, could increase the release of estrogen by the ovaries. This study investigated whether such exposure is associated with an increased risk of breast cancer in women.
Methods: Case patients (n=813), aged 20-74 years, were disgnosed from November 1992 through March 1995; control subjects (n=793) were identified by random-digit dialing and were frequency matched according to 5-year age group. An in-person interview was used to gather information on sleep habits and bedroom lighting environment in the 10 years before diagnosis and lifetime occupational history. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of conditional logistic regression, with adjustment for other potential risk factors.
Result: Breast cancer risk was increased among subjects who frequently did not sleep during the period of the night when melatonin levels are typically at their highest (OR = 1.14 for each night per week; 95% CI = 1.01 to 1.28). Risk did not increase with interrupted sleep accompanied by turning on a light. There was an indication of increased risk among subjects with the brightest bedrooms. Graveyard shiftwork was associated with increased breast cancer risk (OR = 1.6; 95% CI = 1.0 to 2.5), with a trend of increased risk with increasing years and with more hours per week of graveyard shiftwork (P = .02, Wald chi-squared test).
Conclusion: The results of this study provide evidence that indicators of exposure to light at night may be associated with the risk of developing breast cancer.
https://pubmed.ncbi.nlm.nih.gov/11604479/