Breast Cancer & EMFs
- The Melatonin Connection
Melatonin, Tamoxifen, 50-60 Hertz Electromagnetic Fields and Breast Cancer
in Reference to the International Breast Cancer Intervention Study
Prepared by Don Maisch - June 1997
According to recent statistics, breast cancer in Australia effects one in 14
women, kills one in 27 and is increasing at a rate of 3% annually. These figures
reflect a growing community concern and as a consequence, in 1995 the Federal
Government allocated $3 million over a 3 year period, solely for breast cancer
studies.
It is unfortunate however, that apparently no current Australian breast cancer
research is examining the growing evidence that low level exposures to 50-60
hertz electromagnetic fields (EMF) may block melatonin's ability to suppress
breast cancer cells and reduce the pineal gland's nocturnal production of melatonin,
thereby increasing susceptibility to breast cancer. This evidence is supported
by both human and laboratory studies, some of which are summarised in this
paper. Many of these studies are still awaiting the peer review process and
as such do not yet constitute part of the body of substantiated scientific
evidence, often referred to by national and international expert regulatory
groups. The peer review process can take years to complete.
Considering the prevalence of breast cancer in western society and the extensive body of evidence pointing to a connection with EMF exposure, it is the position of this paper that with breast cancer patients, avoiding excessive EMF exposure should be part of the treatment, under the Precautionary Principal, which in this case could be defined as:
The precautionary principal should guide decision-makers when confronted by potential threats to human health. The lack of full scientific certainty should not be used as a reason for postponing measures to prevent exposure to these potential threats. If measures generally reducing exposure can be taken at reasonable expense and with reasonable consequences in all other respects, an effort should be made to reduce exposures to a level below that level which evidence indicates may be harmful to health.
Melatonin
Both human and animal circadian rhythms are driven by the day/night cycle and are synchronized with natural geomagnetic electromagnetic fields. The major control gland over this natural cycle is the pineal gland and its secretion of the neurohormone melatonin. During the day light falling on the eye's retina produces signals which are biochemically amplified to stimulate the pineal gland to reduce its melatonin output. At night the absence of light with sleep stimulates the pineal gland to produce melatonin. The circadian production of melatonin is thought to control important processes in the eyes, including restoration of rods (for night vision) at the end of the night, and renewal of cones (for colour vision) at the end of the day. One theory on how man made EMF's may affect the pineal gland is that the pineal gland may 'sense' EMF's as light and therefore reduce melatonin production. A possible cause for this effect is from insoluble granular material contained within the pineal gland.
Research by Dr. Sidney Lang, an expert on piezoelectricity, which is the production of electric fields by pressure on crystalline structures, has shown that the pineal gland has piezoelectrical activity. Dr Lang hypothesizes that this activity is a function of this granular material and if so it may be responding to narrow wave lenghts. (1)
Once melatonin is produced, its ability to pass through the cell membrane allows it to pass directly into the blood stream. Once in the blood melatonin has access to every cell in the body where it passes through the cell membrane to the cell nucleus, which has receptors for it. A few cell membranes also have receptors for melatonin, which may control the 24 hour circadian rhythm of the endocrine system.
In the cell nucleus melatonin plays a role in regulating gene expression. The ability of melatonin to enter all cells is also essential for one of the other important functions of melatonin, which is to act as a scavenger of highly toxic oxygen-based free radicals. The production of these free radicals is a consequence of the utilization of oxygen by all organisms. About 1 - 2% of inspired oxygen ends up as toxic free radicals which can damage macromolecules such as DNA, proteins and lipids. This damage is referred to as oxidative stress.
Because of its ability to eliminate free radicals, melatonin is probably the most efficient natural cell protection and oncostatic agent in our bodies. At night, melatonin production floods our bodies, eliminating the build up of free radicals that are being produced, allowing the DNA synthesis and cell division to occur with a far lower chance of damage and hence producing more healthy cells. Melatonin also dampens the release of estrogen, prolonged exposure to which may increase the risk of breast cancer. (2)
Tamoxifen
Tamoxifen, which is the most widely used therapy for treatment of breast cancer, has proven effective in treating breast cancer in its early stages, is also used by over one million women throughout the world who have had breast cancer, to prevent its recurrence.
Electromagnetic Fields (EMF)
In 1987 Stephens et al. in the paper, "Electric power use and breast cancer; a hypothesis", suggested that electromagnetic fields (EMF's) reduce melatonin production by the pineal gland and that melatonin suppresses the development of breast cancer. (3)
Other researchers have also hypothesized that the possible suppression of melatonin by electromagnetic fields may provide a single mechanism for explaining how number of different types of cancer could be promoted by EMF's, however this suggestion has been hotly debated due to the previous failure to replicate several key studies. Replication is a key step in the scientific method for it takes an unproven hypothesis to a significant conclusion which can be acted upon.
Research in 1993 by Liburdy, et al. found that melatonin reduces the growth rate of human breast cancer cells (MCF-7) in culture, but that a 12mG 60 Hz magnetic field can block the ability of melatonin to inhibit breast cancer cell growth. (4)
This study has now been replicated four times. It is this replication and the three human exposure studies also mentioned herein, that have significant implications for the successful treatment of breast cancer and calls for immediate action from researchers and oncologists alike. The failure to do so, under the excuse of "more research needs to be done" is not acting in the best interests of breast cancer patients, to say the least.
In June 1996 at the 18th. Annual Meeting of the Bioelectromagnetics Society (BEMS) the following three replicated studies were presented which have important implications in the treatment of breast cancer, and by implication other cancer types as well.
1) ELF INHIBITION OF MELATONIN AND TAMOXIFEN ACTION ON MCF-7 CELL PROLIFERATION; FIELD PARAMETERS. J.D. Harland and R.P. Liburdy. Lawrence Berkeley National Laboratory, University of California, Berkeley, California, USA.
This study was designed to define the parameters by which a 12 milliGauss (mG) 60 Hz magnetic field can block the inhibitory action of melatonin and Tamoxifen, a widely used drug treatment for breast cancer. They found that a 12 mG field can significantly reduce the growth inhibitory action of melatonin and Tamoxifen on human breast cancer cells (MCF-7) in culture.
"Preliminary experiments suggest that at least three days exposure at 12mG is necessary to block the cytostatic action of Tamoxifen (from 27% growth inhibition, p<0.0001; to 5% growth inhibition, p>0.5 ) indicating that prolonged 12mG exposure may be required. This appears to be consistent with a "slow" interaction mechanism. This result also raises the possibility of field effects that may be cell cycle dependent, since measurable effects appear to be delayed or reversible until cell division begins. In addition, all field magnitudes of 12 mG or higher that have been tested thus far (12mG, 20mG, 1Gauss) have been effective at blocking melatonin." (5)
A lower field of 2mG did not have any significant effect, suggesting a threshold might exist between 2 and 12 mG.
2) INDEPENDENT REPLICATION OF THE 12-MG. MAGNETIC FIELD EFFECT ON MELATONIN AND MCF-7 CELLS IN VITRO. C.F.Blackman, S.G. Benane, D.E. House and J.P. Blanchard. National Health & Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, USA.
This study was specifically designed to attempt to replicate the previous study, with the cooperation of the originating laboratory. The results independently confirmed the previous study's findings. As follows:
1) Melatonin can inhibit the growth of human breast cancer cells MCF-7 in culture.
2) A 12 mG 60 Hz magnetic field can completely block melatonin's oncostatic action.
The authors of this study believe these results are particularly significant because these findings represent the first replication of a key magnetic bioeffect, and that these two studies represents a foundation for theorists to generate "testable" hypotheses for biological mechanisms of interaction. (6)
3) INHIBITION OF MELATONIN'S ACTION OF MCF-7 CELL PROLIFERATION BY MAGNETIC FIELDS ASSOCIATED WITH VIDEO DISPLAY TERMINALS: A PRELIMINARY STUDY. S.M.J. Afzal and R.P. Liburdy. Lawrence Berkeley National Laboratory, University of California, USA.
This study was undertaken to test the hypothesis that ELF and VLF magnetic fields associated with Video Display Terminals (VDT's) influence human breast cancer cell growth in vitro by altering melatonin's natural oncostatic activity. This hypothesis was based on the findings of the two previously mentioned studies.
The conclusions of this study appear to suggest that 12 mG VDT magnetic fields also inhibit the oncostatic action of melatonin in vitro and that the magnetic field component was the operative factor in the 12 mG 60 Hz exposures. Preliminary data from two seperate experiments indicated significant growth inhibition (33% and 22%) on day 6 in the 2 mG magnetic field conditions.(7)
A fourth replication study of a 12 mG effect on MCF-7 breast cancer cells was presented at San Antonio Texas in Nov.1996 by Dr Richard Luben, as follows:
4) REPLICATION OF 12 mG EMF EFFECTS ON MELATONIN RESPONSES OF MCF-7 BREAST CANCER CELLS IN VITRO . R.A. Luben, S.Saraiya and A.P. Morgan. Division of Biomedical Sciences, University of California, Riverside, California 92521, USA.
The objective of this study was to replicate, with the cooperation of the originating laboratories, the studies conducted by Liburdy and Blackman.
They "found that exposure of breast cancer cells to 12 mG 60 Hz EMF induced a reproductable net increase (mean +28%, p<0.001) in the growth rate of MCF-7 cells treated with a physiological dose of melatonin. This constitutes a replication of the observations reported previously by Liburdy and Blackman, in that EMF produced a blocking of the anti-cell-growth effects of melatonin. There are some variations between our findings and theirs: . . ."Nevertheless, the net differences between (melatonin+EMF)and (melatonin-EMF) groups is both qualitatively and quantitively consistent in all the studies. . ." (8)
It does not necessarily mean that these in vitro study conclusions can be directly applied to breast cancer patients. However it is important to note that some recent human exposure studies also indicate a melatonim/EMF effect, and that levels of 12 mG or higher can be routinely encountered in daily life, for example, electric blankets can give emissions in excess of 12 mG. Sleeping with an electric blanket on is a special concern, as it is at night that the pineal gland, located near the centre of the brain, produces melatonin. In the study by Liburdy and Harland, indications were that a prolonged exposure may be required, which is a further possible implication of electric blanket use while sleeping.
In a study by Yaofei Liu and Dr. Indra Chatterjee at the University of Nevada they found that with electric blankets, "The average current density (induced in the body) in the head is higher than the torso because of the smaller cross section of the head."(9)
Studies by B. Wilson et al at Battelle Pacific Northwest Laboratory have shown that melatonin synthesis is altered by exposure of animals to ELF electromagnetic fields, and he and others have proposed that disruption of the normal daily cycles of melatonin synthesis could be a risk factor for human breast cancer. (10) Battelle is currently running a replication study on the above mentioned three studies.
In a soon to be published follow up study by Dr. Henry Lai and Dr. Narendra Singh, who earlier found single and double strand DNA breaks in rats exposed to low level radiofrequency radiation (RFR) after a single two hour exposure, the treatment of either melatonin or a free radical scavenger (PBN) to the exposed rats immediately before and after RFR exposure prevented the DNA damage. (11) This indicates the importance of melatonin in DNA repair mechanisms, and therefore in cancer suppression, but not that the RFR is effecting is the rats own pineal melatonin production. The current body of evidence examines Extremely Low Frequency (ELF) 50-60 Hz fields and its effects on melatonin. At this point in time evidence for a similar effect from RFR does not exist. (12)
In a study by Tan et al in 1993, rats were injected with a chemical carcinogen, Safrole which damages DNA by inducing the production of large numbers of free radicals. Rats injected with Safrole were found to have extensive DNA damage after 24 hours. When melatonin was also injected, the DNA damage was reduced by 99%. (13)
A preliminary study of 60 workers at a Finnish garment factory found "a highly significant effect"of EMF's in reducing nocturnal melatonin levels. Magnetic field measurements were taken for the two types of machines used in the factory and operators were assigned to high or low exposure groups, based on the type of machine they were using, with average exposures either above of below 10 milliGauss. Unexposed non industrial workers were used as controls.
The results of this study found strong effects of both magnetic field exposure and smoking on night time levels of melatonin. No difference was found in melatonin levels on week nights and Sunday nights, indicating "that the possible suppression caused by magnetic field exposure is chronic, with little recovery during the weekend." (14) - consistent with the effect of chronic electric field exposure in the rat experiments of Wilson et al. (1986) (15)
In a study of 192 electric utility workers, Drs. John Reif and James Burch, from the Colorado State University, found that some EMF exposures are associated with lower levels of melatonin. They found a significant association between magnetic field exposures and lower daytime melatonin levels on the second and third of three days of measurement. The lack of an effect on the first day (following a weekend or equivalent) may indicate a cumulative effect of exposure. Some studies have suggested that EMF effects on melatonin may depend on whether the field is continuous or intermittent. Reif and Burch found that magnetic fields in the home that were "temporally coherent"(less intermittent) had a very significant association with lower melatonin levels at night. They concluded that, "The intensity and temporal characteristics of magnetic fields appear to be involved in melatonin suppression." (16)
Office workers who used computer monitors (VDU's) had a significant reduction in circulating levels of melatonin over a course of the working day, according to a study by researchers Drs. Bengt Arnetz of the Karolinska Institute, and Mats Berg of the Karolinska Hospital in Stockholn Sweden. No such change was found during days at the office with no VDU use. According to the researchers; "This suggests that there is a direct impact from the electromagnetic environment of the VDU on levels of melatonin." Levels of a different hormone, adrenocorticotropic hormone (ACTH), went up during the working day and this showed a strong correlation with worker's subjective assessment of mental strain. Arnetz and Berg note that ACTH is "known as a classic stress hormone that reacts to mental strain." But in contrast, "occupational strain did not correlate with melatonin levels." (17)
This finding supports the Boston University breast cancer study, in which Patrica Coogan and co-workers found a 43% increase in breast cancer among women with a high potential for occupational exposures to magnetic fields, notably those working with main-frame computers. In an interview with Microwave News, Coogan said,"This study lends credence to the idea that EMF's might influence breast cancer." (18)
Not all human exposure studies found a melatonin reduction effect. A study by Dr. Charles Graham et al at the Midwest Research Laboratory in Kansas City, MO. conducted for the Electric Power Research Institute (EPRI), found that a continuous 60 Hz, 200 mG magnetic field applied to people while they slept had no effect on nocturnal melatonin levels.
In a similar study published in 1994, Graham found no overall effect for intermittent EMF exposures, however, date from that study showed that men with preexisting low levels of melatonin had even lower levels when exposed to EMF's, suggesting that a person's prior melatonin level may be an important factor. Later research by Graham failed to replicate this finding however.
Graham cautions against a conclusion that EMF's do not effect melatonin. He points out that all of the volunteers in his studies were "healthy young men", and that the types of EMF's with which people come in contact in an industrialised society are much more varied than those created in the carefully controlled MRI exposure facility. (19)
In relation to this, Dr John Reif of Colorado State University comments,"Most natural observations appear to find melatonin changes, while controlled lab studies tend not to. . . In a general way, I'm concerned that the controlled lab trials may not mimic exposures in the real world."(20)
The International Breast Cancer Intervention Study
This study, which has been running for five years now, is aimed at discovering if the drug Tamoxifen can help prevent the disease in those who have not yet developed it but are at increased risk.
Women from the UK, Europe, New Zealand and Australia are participating in the study, which is open to women aged between 35 and 70 who have a strong family history of breast cancer.
Those aged 45 to 70 must have had a close family member diagnosed with breast cancer at the age of 50 or under, or in both breasts at any age, or must have two close blood relatives who have had breast cancer at any age. Those aged 35 to 45 must have had a close family member diagnosed with breast cancer before 40 or at least two close blood relatives who have had breast cancer before 50.
Each participant is encouraged to continue with the study for 5 years. During that time they take one tablet, which is either Tamoxifen or a placebo, each day and receive a clinical assessment every six months and a mammogram each year. If Tamoxifen is proved effective it could ultimately be provided to women at increased risk.
Considering the above mentioned studies, especially the study by Liburdy and Harland, "ELF Inhibition of Melatonin and Tamoxifen Action On MCF-7 Cell Proliferation; Field Parameters", which found that a 12 mG magnetic field can significantly reduce the growth inhibitory action of melatonin and Tamoxifen, participants EMF exposures should be included in the International Breast Cancer Intervention Study as a possible confounding factor. If EMF exposures are a possible confounding factor, the statistical model for analysis of the study should take into account this possible factor. If not, the possible EMF factor may put enough statistical noise to the study that the conclusions may well be affected as the effectiveness of Tamoxifen may be reduced in those participants with relevant EMF exposures.
If environmental EMF's, and electric blanket use are a confounding factor, this should be possible to check by questioning the subjects on their habits, maybe even taking home and workplace EMF exposure readings. If some participants are found to be exposed to prolonged EMF exposures in the order of 2 to 12 milliGauss (there appears to be a dose-response relationship from 2 to 12 milliGauss) it may be necessary to advise them to avoid these exposures.
It may also be advisable to do actual measurements of melatonin levels in those subjects identified as being prone to breast cancer. Women with breast cancer have shown a lower nocturnal increase in melatonin levels than control women. (21)
In the September 1996 issue of Epidemiology, Susan Preston-Martin reviews much of the data on topic. She also calls for including melatonin levels in breast cancer risk assessment studies and for obtaining an ELF exposure history.
A possible avenue for research would be to determine if the use of melatonin would have a similar protective effect as Tamoxifen, as breast cancer patients may have a better prognosis if their melatonin levels are high.(22)
Also on the Liburdy and Harland study: what do Tamoxifen and melatonin have in common, and why is their effectiveness mitigated by exposure to EMF's?
Professor Russell Reiter who has been researching the effects of EMF's on melatonin production has done a review paper on this subject. This review paper was prompted by a number of epidemiological studies in which an increased incidence of cancer was reported in individuals living or working in an environment of higher than normal artificial electromagnetic fields. His paper extract concludes with the following observation:
"Reduction of melatonin at night, by any means, increases cell's vulnerability to alteration by carcinogenic agents. Thus, if in fact artificial electromagnetic field exposure increases the incidence of cancer in humans, a plausible mechanism could involve a reduction in melatonin which is a consequence of such exposures."
Dr. Reiter also notes:
" Epidemiologists should look for other possible changes, including psychological depression, fatigue, sleep inefficiency, chronic feelings of jet lag, endocrine disturbances and other symptoms; all these may result from a chronically low melatonin rhythm." (23)
As a result of his latest study Dr. Reiter now proposes that melatonin is "more rapidly taken up into tissues during the exposure." He noted that if EMF's result in higher levels of free radicals, then an antioxidant like melatonin "would disappear from the blood more quickly than is normal because it would be required for the scavenging of free radicals." (24)
If Reiter's hypothesis is correct, then prolonged exposures may tax the pineal gland's ability to maintain adequate levels of melatonin to cope with the extra stress created by EMF exposure, and also Tamoxifen's ability to inhibit the growth of breast cancer cells.
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REFERENCES
E-mail correspondence with Dr. John Goldsmith, Head of the Epidemiology and Health
Services Evaluation UNIT, Faculty of Health Sciences, Ben Gurion University,
Isreal. He is author of Epidemiologic Evidence of Radiofrequency Radiation
(Microwave) Effects on Health in Military, Broadcasting, and Occupational
Studies. (1995)
Cherry N. (1997) Potential and Actual Effects of Radiofrequency and Microwave
Radiation at levels Near and Below 2uW/cm2 . p.10 - 13.
Stevens R.G. (1987) "Electric power use and breast cancer: a hypothesis",
American Journal of Epidemiology, 125: p.556 - 561.
Liburdy R.P. et al (1993) "ELF magnetic fields, breast cancer and melatonin:
60 Hz fields block melatonin's oncostatic action on ER+ breast cancer cell
proliferation". Journal of Pineal Research, 14 (2): p.89 - 97.
Harland J.D., Liburdy R.P. (1996) ELF Inhibition of Melatonin and Tamoxifen
Action on MCF-7 Cell Proliferation: Field Parameters. BEMS Meeting Victoria,
British Columbia, Canada. Abstract A-1-1.
Blackman C.F. et al (1996) Independent Replication of the 12 mG Magnetic Field
Effect on Melatonin and MCF-7 Cells in vitro. BEMS Meeting, Victoria British
Columbia, Canada. Abstract A-1-2.
Liburdy R.P., Afzay S.M.J. (1996) Inhibition of Melatonin's Action ofMCF-7
Cell Proliferation by Magnetic Fields Associated with Video Display Terminals:
A Preliminary Study. BEMS Meeting, Victoria, British Columbia, Canada Abstract
A-1-3.
Luben R.A., Saraiya S. and Morgan A.P. (1996) Replication of 12mG EMF Effects
on Melatonin Responses of MCF-7 Breast Cancer Cells in vitro , Annual Review
of Research on Biological Effects of Electric and Magnetic Fields from
the Generation, Delivery & Use of Electricity, San Antonio, Texas;
Nov. 19 - 21 1996. Abstract A-1. Health
Physics , Nov. 1996, p. 676-684.
EMF Health Report, (Information Ventures, Inc.) Jan/Feb. 1997, p. 7.
E-mail abstract of paper by Henry Lai, (in press) Bioelectromagnetics.
E-mail correspondence with Dr. John Goldsmith, as above.
Cherry N. (1997) Potential nd Actual Effects of Radiofrequency and Microwave
Radiation at levels Near and Below 2uW/cm2. p.14.
Microwave News, Mar/Apr. 1997, p. 3-4.
Wilson B.W., Chess E.K. and Anderson L.E. (1986) "60 Hz Electric Field
Effects on Pineal Melatonin Rhythms: Time Course and Onset of Recovery".
Bioelectromagnetics, 7:p. 239-242.
Microwave News, as above.
Coogan P.F. et al (1996) "Occupational
Exposure to 60 -Hertz Magnetic Fields and Risk of Breast Cancer in Women".
Epidemiology; 7:p.459-464. also: Microwave News, Sept/Oct. 1996, p.1.
Microwave News, as above.
Microwave News, as above.
Stevens R.G. (1987) "Electric power use and breast cancer: a hypothesis",
American Journal of Epidemiology, 125: p.556 - 561.
Stevens R.G., Davis S., Thomas D.B., AndersonL.E., Wilson B.W.(1992) "Electric
Power, Pineal Function and the Risk of Breast Cancer: A Hypothesis", FASEB
Journal.6: p. 853-860.
Reiter RJ., (1994) "Melatonin Suppression
by Static and Extremely Low Frequency Electromagnetic Fields: Relationship
to the Reported increased incidence of cancer", Reviews on Environmental
Health. 10(3-4):p.171-186.
Microwave News, as above.