Report of an independent Advisory Group on Non-ionising Radiation

Foreword

Until 1 April 2005, the National Radiological Protection Board (NRPB) had a statutory responsibility for advising UK government departments on health effects and standards of protection for exposures to ionising and non-ionising radiations. This responsibility now lies with the Radiation Protection Division (RPD) of the Health Protection Agency (HPA).

In 1990, to provide support for the development of advice on non-ionising radiations, the Director of the NRPB set up an Advisory Group on Non-ionising Radiation with terms of reference:

‘to review work on the biological effects of non-ionising radiation relevant to human health and to advise on research priorities’

The Advisory Group was reconstituted in 1999 as an independent body and now reports directly to the Board of the HPA. Its current membership is given on page 3 of this report. For details of its current work programme, see the website www.hpa.org.uk.

The Advisory Group has, to date, issued a number of reports concerned with exposures to electromagnetic fields. It has considered their possible association with an increased risk of cancer, including childhood leukaemia. It has also reported on health effects related to the use of visual display units, on neurodegenerative disease and on corona ions and increased particle deposition near power lines. The Advisory Group has also considered the potential health effects of radiofrequency fields. Details of publications by the Advisory Group are given in an appendix.

In this report the Advisory Group considers the available scientific evidence from studies with humans, animals and cells relating to power frequency electromagnetic fields, melatonin and the risk of breast cancer.

Summary

Exposure to power frequency electromagnetic fields (EMFs) is ubiquitous in modern life. The hypothesis that chronic exposure to EMFs may increase the risk of breast cancer, via a reduction in secretion of the hormone melatonin from the pineal gland, was first made almost 20 years ago, and has led to a great deal of research. To review this hypothesis, this report addresses evidence on three issues, namely, whether:

  1. (a)  EMFs affect the production or action of melatonin,
  2. (b)  melatonin affects the risk of breast cancer,
  3. (c)  EMFs affect the risk of breast cancer.

Investigations using cells, animals and humans have not given consistent or convincing evidence that EMF exposure affects melatonin production or action. However, there are deficiencies in the existing research, which leave open the possibility of an effect.

There is stronger evidence that melatonin can inhibit the growth of cancer cells in laboratory culture and in animals. Data on the possible relation of melatonin levels to risk of subsequent breast cancer in humans are limited and inconclusive. Studies investigating the effect of light exposure (which affects melatonin) on breast cancer risk in humans have given some evidence for an association, but left it unclear whether, if there is an association, it is causal in nature.

There is no consistent evidence, from research using cells, animals and humans, that EMF exposure is a cause of breast cancer, nor has any mechanism for such an association been demonstrated.

The report concludes with recommendations for further research.

Overall, the evidence that melatonin, and the timing and extent of light exposure, may affect breast cancer risk is intriguing but not conclusive. In aggregate, the evidence to date does not support the hypothesis that exposure to power frequency EMFs affects melatonin levels or the risk of breast cancer.

1 Introduction

Exposure to power frequency electromagnetic fields (EMFs) is ubiquitous in modern life. Sources of exposure include the national grid system, the local electricity supply network, and mains wiring in homes, offices and other buildings. In addition, EMFs are produced by all machines, appliances and devices powered by electricity: electric fields are related to voltage differences, whereas magnetic fields are associated with the flow of electric current.

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In recent years there has been concern about possible health effects of exposure to EMFs arising from the electricity supply system (50 Hz in the UK) and in particular about a possible increased risk of childhood leukaemia. This has been a public issue in many countries and been the subject of a number of national and international reviews (eg Ahlbom et al, 2000; IARC, 2001).

The suggestion has also been made that exposure to EMFs may increase the risk of breast cancer. This was first made almost 20 years ago, and has led to a great deal of research: melatonin, a hormone produced by the pineal gland in the brain, has been suggested as playing a pivotal role in this.

The purpose of this report is to consider the available scientific evidence from studies with humans, animals and cells relating to power frequency EMFs, melatonin and the risk of breast cancer. Specifically, it has addressed three questions, namely, whether:

  1. (a)  EMFs can affect the production or action of melatonin,
  2. (b)  melatonin can affect the risk of breast cancer,
  3. (c)  EMFs can affect the risk of breast cancer.

1.1 Background to the report

Melatonin is a hormone produced by the pineal gland in a distinct daily rhythm governed by daylength. Levels of melatonin in the blood are very low during the day and are elevated at night in all animals, including humans (Arendt, 1995). Melatonin has been shown to influence the control of daily activities such as the sleep/wake cycle and seasonal rhythms such as those of reproduction in animals that respond to daylength. It has been found to diminish the effect of some chemical carcinogens on mammary tissue in animal experiments and to reduce the rate of growth of human breast cancer cells in culture.

Cohen and colleagues first proposed the hypothesis that diminished function of the pineal gland may promote the development of human breast cancer (Cohen et al, 1978). In addition, Stevens (1987) suggested that chronic exposure to electric fields (or to visible light at night) may reduce melatonin secretion by the pineal gland and so increase the risk of breast cancer.

Taken together, these ideas form the basis of the so-called melatonin hypothesis, which attempts to link electrical power use with increased risk of breast cancer via melatonin. This hypothesis has aroused wide interest and attention and has stimulated considerable experimental and epidemiological research.

1 INTRODUCTION

Given the diversity of effects caused by melatonin and the complexity of its actions, long-term changes in this hormone might have wide ranging consequences for health. It has been proposed that these might include altered incidence of solid tumours or leukaemias, as well as effects on ageing and neurodegenerative diseases. While these endpoints are of potential interest, most melatonin-related EMF research has been focused on breast cancer.

As part of a previous comprehensive evaluation of the potential of power frequency EMFs to cause cancer, the Advisory Group on Non-ionising Radiation (AGNIR) concluded that melatonin rhythms were not substantially affected by exposure to magnetic fields (AGNIR, 2001), although the preliminary data from one investigation suggested some effects may occur, possibility in a sensitive subgroup of the study population. Since the publication of that report, further studies have been published relevant to an understanding of possible effects of EMFs on melatonin. As a consequence, the Board of the NRPB asked the Advisory Group to examine the evidence related to effects of EMFs on the production of melatonin and to advise on whether this could be implicated in the development of breast cancer.

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1.2 Structure of the report

The report has been written in eight chapters. Following this introduction which provides an overall background and perspective to the report, the next two chapters give further background information important to the interpretation of the epidemiological and experimental evidence.

Chapter 2 describes the main physical characteristics of EMFs and common sources of exposure. The likely size of the fields in various residential and occupational settings is considered, as are fluctuations in exposure that occur during the day and night. Exposure to either an electric or magnetic field will induce electric fields and currents in biological tissues that depend on the magnitude of the external field.

Chapter 3 reviews the basic physiology of the pineal gland and its role in the production and secretion of melatonin into the blood. The roles of melatonin in reproductive and other seasonal functions that depend on the response of organisms to the length of the day are discussed as well as those such as sleep activity that have a near 24 hour period (circadian rhythm). The characteristics of melatonin production in humans and the effects of melatonin treatment are also described.

In addition, there is compelling evidence that hormones substantially influence the development of breast cancer. This evidence is reviewed in Chapter 3 together with information on the possibility that melatonin may mediate or interact with the mechanism of sex hormone action. A range of other possible mechanisms have been postulated whereby melatonin could influence cell growth and differentiation, through changes in the communication between cells, and in the immune system. These possibilities are also reviewed, as are melatonin receptors and their pharmacology.

The next three chapters consider the experimental and epidemiological evidence for each of the three main themes of the report. The experimental studies are further divided into investigations using cultures of cells (in vitro studies), studies using animals (in vivo studies), and studies using human volunteers.

Chapter 4 considers the effect of EMFs on melatonin production and action. If exposure to EMFs is to influence the development of cancer through an effect on melatonin secretion, then an understanding of how such fields may influence melatonin is essential.

The in vitro evidence divides into two types of study: those investigating effects on the production of melatonin by cultures of pineal cells, and those investigating effects on the action of melatonin on cells. Most in vivo studies have used rats and mice, although some studies have used Djungarian hamsters. Very few data have been obtained using non-human primates. Laboratory-based studies in humans investigating the effects of exposure to magnetic fields are described. Few of these studies, however, have used appropriate control procedures or monitored conditions sufficiently to enable the potential of magnetic fields to be properly assessed. Only a few epidemiological studies on EMF exposures and melatonin have been published. These are mainly concerned with melatonin levels in relation to residential exposures in women, and occupational exposures in both women

and men.

Chapter 5 explores the relationship between melatonin and risk of breast cancer. As indicated above, the potential relationship between melatonin and the development of cancer is a subject that has aroused much interest after early work suggesting that pineal secretions decreased the rates of cell proliferation and transformation. In vitro studies of melatonin and breast cancer that have focused on this aspect are reviewed: more than 60 in vitro studies have been published, with the vast majority using the same breast cancer cell line (MCF-7) that was first described in 1973.

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The potential of melatonin to modulate the incidence and growth of mammary tumours in various animal models of breast cancer is also reviewed. Most of these studies have assessed the effects of melatonin treatment on the growth of chemically induced mammary tumours; however, a few studies investigated effects on transplantable tumours, while others used normal and transgenic mouse strains that express a high spontaneous incidence of mammary tumours. Further studies are described that investigated the effects caused by inducing changes in pineal function either by removing the pineal gland (pinealectomy) or by altering the apparent day length.

Studies assessing melatonin secretion in breast cancer patients and in individuals without cancer are also reviewed in Chapter 5. These studies are difficult to interpret because the presence of breast cancer may have affected melatonin levels, and also because many of the studies lack control of potentially confounding factors that may affect melatonin secretion. Two cohort studies have given data on risk of subsequent breast cancer in women for whom information was available on urinary melatonin metabolite levels; these are reviewed. Epidemiological studies of several groups thought to have an unusual extent or timing of light exposure, as for instance shift workers or blind women, are also reviewed for evidence that might be relevant to the melatonin hypothesis. None of these latter studies, however, has furnished any data directly on melatonin levels.

Chapter 6 considers whether EMFs can affect the risk of breast cancer. Previously, the Advisory Group (AGNIR, 2001) concluded that there was no convincing evidence that exposure to EMFs at levels likely to be encountered directly damaged DNA (ie was genotoxic) or that EMFs could bring about the transformation of cells in culture. EMFs were therefore considered unlikely to initiate cancer. Since the completion of that report, some in vitro studies specifically relevant to breast cancer have been published; these newer studies are reviewed.

Although limitations exist in using carcinogen-induced rodent models of breast cancer, they are a widely used assay, and a number of animal studies are described which have used such models to study the effects of magnetic fields on mammary tumour development.

STRUCTURE OF THE REPORT

1 INTRODUCTION

The final part of Chapter 6 considers the relation of EMF exposure to risk of female breast cancer. This includes the studies of breast cancer risks in women in relation to residential proximity to electricity transmission power lines, and to use of electric blankets.

The principal conclusions of the Advisory Group are given in Chapter 7, and the report finishes with recommendations for further research in Chapter 8. A glossary of less familiar scientific terms is also included.

1.3 References

AGNIR (2001). ELF electromagnetic fields and the risk of cancer. Report of an Advisory Group on Non-ionising Radiation. Doc NRPB, 12(1), 1–179.

Ahlbom A, Day N, Feychting M, Roman E, Skinner J, Dockerty J, Linet M, McBride M, Michaelis J, Olsen JH, Tynes T and Verkasalo PK (2000). A pooled analysis of magnetic fields and childhood leukaemia. Br J Cancer, 83(5), 692–8.

Arendt J (1995). Melatonin and the Mammalian Pineal Gland. London, Chapman Hall.
Cohen M, Lippman M and Chabner B (1978). Role of pineal gland in aetiology and treatment of breast cancer.

Lancet, 2(8094), 814–16.

IARC (2001). Non-ionizing radiation, Part I: Static and extremely low frequency electric and magnetic fields. IARC Monographs on the Evaluation of Carcinogen Risks to Humans, Volume 80. Lyon, World Health Organization/International Agency for Research on Cancer.

Stevens RG (1987). Electric power use and breast cancer: a hypothesis. Am J Epidemiol, 125, 556–61.

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