- Email: [email protected]
Current thinking about risks from currents
COMMENTARY
NASCET.6 Analysis of these data also showed that the benefit from surgery was greatest among patients aged over 75 (figure).7 The number of patients in this age-group was small, even with all trials combined, but the overall findings (a high risk of stroke without surgery, but no increase in operative risk) were similar in the two largest trials. Should symptomatic carotid disease therefore be investigated and treated more actively in the very elderly? This decision depends on the extent to which the trial results can be generalised to routine clinical practice. Since patients who enter RCTs are generally healthier than those who do not,8 and the endarterectomy trials also actively excluded patients with severe concurrent disease, the trial populations will not have been typical of routine clinical practice. However, this observation does not necessarily invalidate the findings. In patients 75 years and older the increased risk of stroke without surgery (figure) is consistent with findings from community-based incidence studies,9 and the acceptable operative risk is consistent with recent non-trial series.10–12 Although a systematic review of studies of the risk of stroke and death due to endarterectomy did report high risks in patients aged over 75 years compared with younger patients, the differences in absolute risk were only 1–2%.13 Even if the operative risk of stroke and death for very old people is as much as 10%, which is higher than is generally reported,10–13 endarterectomy would still be beneficial because of the high risk of stroke without surgery. Endarterectomy in routine clinical practice is therefore likely to benefit reasonably fit patients over 75 years old. However, the population has aged in the 15 years since the endarterectomy trials began recruitment, and continues to do so. In France, for example, the number of centenarians is about 8500, but will increase to 41 000 by 2025 and 150 000 by 2050.14 The clinical dilemma is now whether to operate on patients aged 85, 90, or even older.10–12 Not one of the 6092 patients in the CETC were over 90, and so treatment decisions in the very elderly currently have to be made without trial data. It is important, therefore, that RCTs in progress, such as local vs general anaesthetic for endarterectomy ([email protected]), endarterectomy vs medical treatment for asymptomatic carotid stenosis ([email protected]), and endarterectomy vs angioplasty and stenting ([email protected]) do recruit such very elderly patients. Finally, one justification for a less aggressive approach to disease prevention in the elderly has been that they will not survive long enough to benefit. However, this assumption does not stand up to scrutiny. The average life-expectancy at age 85 in the USA, for example, is 6 years. The reduction in stroke risk after endarterectomy for severe symptomatic carotid stenosis is evident within 6 months of surgery and peaks by 2 years.3,4 Most 85-year-olds would therefore survive long enough to benefit. Indeed, in some series, survival after endarterectomy is independent of age because of the high risk of cardiac death in young patients with severe arterial disease.11,12 Elderly patients commonly do not wish to undergo endarterectomy, but they should at least be given the choice. The trial evidence suggests that they are likely to benefit, and the operative risks reported are acceptable.10–13 It is therefore difficult to justify not investigating carotid disease in an otherwise fit elderly patient who is willing to consider surgery and who has an appropriate risk profile.15 Peter M Rothwell Department of Clinical Neurology, University of Oxford, Radcliffe Infirmary, Oxford OX2 6HE, UK (e-mail: [email protected])
THE LANCET • Vol 357 • April 14, 2001
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Dunlop WE, Rosenblood L, Lawrason L, Birdsall L, Rusnack CH. Effects of age and severity of illness on outcome and length of stay in geriatric surgical patients. Am J Surg 1993; 165: 577–80. Burns-Cox N, Campbell WB, Van Nimmen BAJ, Vacaeren PMK, Lucarotti M. Surgical care and outcome for patients in their nineties. Br J Surg 1997; 84: 496–98. European Carotid Surgery Trialists’ Collaborative Group. Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet 1998; 351: 1379–87. North American Symptomatic Carotid Endarterectomy Trialists’ Collaborative Group. The final results of the NASCET trial. N Engl J Med 1998; 339: 1415–25. Oxman AD, Guyatt GH. A consumers guide to subgroup analysis. Ann Intern Med 1992; 116: 78–84. Rothwell PM, Gutnikov SA, Eliasziw M, et al for the Carotid Endarterectomy Trialists’ Collaboration. Meta-analysis of individual patient data from randomised controlled trials of carotid endarterectomy for symptomatic stenosis: (1) Patients and methods. Cerebrovasc Dis 2000; 10 (suppl 2): 77. Rothwell PM, Mayberg MR, Warlow CP, Barnett HJM for the Carotid Endarterectomy Trialists’ Collaboration. Meta-analysis of individual patient data from randomised controlled trials of carotid endarterectomy for symptomatic stenosis: (3) The efficacy of surgery in important pre-defined subgroups. Cerebrovasc Dis 2000; 10 (suppl 2): 108. Stiller CA. Centralised treatment, entry to trials and survival. Br J Cancer 1994; 70: 352–62. Bonita R. Epidemiology of stroke. Lancet 1992; 339: 342–47. Perler BA, Dardik A, Burleyson GP, Gordon TA, Williams GM. Influence of age and hospital volume on the results of carotid endarterectomy: a statewide analysis of 9918 cases. J Vasc Surg 1998; 27: 25–31. Van-Damme H, Lacroix H, Desiron Q, Nevelsteen A, Limet R, Suy R. Carotid surgery in octogenarians: is it worthwhile? Acta Chir Belg 1996; 96: 71–77. Thomas PC, Grigg M. Carotid surgery in the octogenarian. Aust N Z J Surg 1996; 66: 231–34. Rothwell PM, Slattery J, Warlow CP. A systematic review of clinical and angiographic predictors of stroke and death due to carotid endarterectomy. BMJ 1997; 315: 1571–77. Dinh QC. Projection de la population totale pour la France metropolitaine: Base RP90, Horizons 1990–2050. Demographie Societe No. 44, INSEE, 1995, Paris. Rothwell PM, Warlow CP on behalf of the ECST Collaborators. Prediction of benefit from carotid endarterectomy in individual patients: a risk-modelling study. Lancet 1999; 353: 2105–10.
Current thinking about risks from currents The production, transmission, distribution, and use of electricity generate electromagnetic fields having a frequency of 50–60 Hz, sometimes called power frequency. This range falls within the extremely lowfrequency band (ELF-EMF). The hypothesis that exposure to such fields increases the risk of cancer has been controversial ever since a link was reported more than two decades ago.1 The main reason for scepticism has been the low amount of energy that these fields transfer because of their low frequency; the wave-length corresponding to 50 Hz is similar to the radius of the earth. The only established mechanism for biological effects of ELF-EMF is induction of electrical currents in the tissue, but the fields to which a person is normally exposed in the environment are generally orders of magnitude too low to be of any significance in this context, in view of the endogenous electrical activity in nerve and muscle cells. These considerations have led physicists to claim that ELF-EMF cannot produce biological effects at the low levels of environmental exposure. Modern society is inconceivable without electricity, so exposure to ELF-EMF is ubiquitous, which is one reason why research on ELF-EMF and health risks has continued despite the limited biophysical plausibility. 1143
For personal use. Only reproduce with permission from The Lancet Publishing Group.
COMMENTARY
Another reason is that scientists have been intrigued by the hypothesis, and to no small extent by some of the findings. The research programmes have included cellular research, animal experiments, studies on human volunteers, and epidemiology. Despite much activity in all these scientific branches, the epidemiological findings have been the driving force because they have been more reproducible than the experimental findings, and because they have made it possible to gradually narrow down the area of interest. Last month the UK National Radiological Protection Board published a comprehensive evaluation of the scientific evidence on ELF-EMF and cancer.2 The report, by an expert group led by Sir Richard Doll, concludes: “Laboratory experiments have provided no good evidence that extremely low frequency electromagnetic fields are capable of producing cancer, nor do human epidemiological studies suggest that they cause cancer in general”. However, the group also writes: “Recent large and well-conducted studies have provided better evidence than was available in the past on the relationship between power frequency magnetic field exposure and the risk of cancer. Taken in conjunction they suggest that relatively heavy average exposure of 0·4 µT or more are associated with a doubling of the risk of leukaemia in children under 15 years of age. The evidence is, however, not conclusive”. The epidemiological studies that have been conducted during the past two decades have gradually improved and recent studies from the USA, Canada, and the UK have been particularly informative.3–5 The improvement has been especially true for exposure assessment: 20 years ago there were no instruments that could be used in epidemiological studies to assess magnetic fields over periods of time. Rather than making the original observation go away, the better studies have generally confirmed it as far as childhood leukaemia is concerned, at least according to the expert group. The group, however, makes the qualification that the evidence for an association is limited to fairly high exposures—in fact at levels so high that in the UK only 0·5% of the population is estimated to face such exposures.5 For other types of cancer that were also implicated in earlier research, such as brain tumours and leukaemia in adults, the expert group finds the evidence unconvincing. The expert group relies to some extent on two pooled analyses with similar results, one conducted by a group led by one of us.6,7 Both these used primary data from the studies pooled. Going back to primary data was essential mainly because it enabled analysis for exposure levels at which individual studies did not have sufficient numbers of subjects for meaningful analyses. In neither of these pooled analyses was there any evidence of an effect to speak of at exposures below 0·3–0·4 µT; above that level both pooled analyses showed clear effects. In our study the relative risk was 2·0 (95%CI 1·3–3·1) for exposures at or above 0·4 µT, an effect that is not likely to be explained by chance. The expert group also noted that we stratified the studies in our pooled analysis into two groups: one group was dominated by recent large studies with direct exposure assessments but with a potential for selection bias, whereas the other group consisted of smaller studies done perhaps with less refined methods for measuring exposure but with little or no potential for selection bias. The pooled results were virtually the same within these two strata. Thus, these two groups of studies mutually support each other’s findings. One cannot, however, exclude the possibility that the findings are due to 1144
selection bias in the first group of studies and random variation in the second group of studies. Therefore, the evidence for an effect of ELF-EMF on risk of childhood leukaemia remains unconvincing. The fundamental question of how magnetic fields would exert an effect on cancer risk is still unresolved, as the expert group notes. Large-animal studies have yielded negative results. In-vitro studies and studies in volunteers have perhaps shed glimmers of light—eg, with suggestions that calcium flux, gene expression, or melatonin production might be involved in the pathogenesis of the cancer. The reports, however, have been notoriously difficult for other laboratories to confirm, and there is still no strong candidate for a mechanism behind a possible ELF-EMF and cancer effect. So not only do the epidemiological results lack support from theoretical physics but also from experiments on cells, animals, and human volunteers. Yet the results remain. With childhood leukaemia having an incidence rate of 4/100 000 children per year and with fewer than 1% exposed, at least in the UK, few children would be affected. These small numbers in no way make the problem negligible. A thorough risk evaluation would require more data than is available, not only with respect to whether or not magnetic fields can produce cancer but, if so, also with respect to the nature of the doseresponse curve and the occurrence and distribution of the relevant exposure; the very high costs of reducing exposures (for example, from existing power lines) have to be factored in. If action has to be taken on data at hand perhaps the recommendations released by the Swedish government some years ago are worth revisiting.8 In essence they recommend that unnecessary heavy exposures be avoided if it is possible without excessive costs or technical difficulties. Such advice is not very different from the recommendations issued by the US National Institute for Environmental Health Sciences 2 years ago: “However, because everyone . . . is . . . exposed, . . . passive regulatory action is warranted”.9 *Anders Ahlbom, Maria Feychting Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden (e-mail: [email protected]) 1 2
3
4
5
6
7
8
9
Wertheimer N, Leeper E. Electrical wiring configurations and childhood cancer. Am J Epidemiol 1979; 109: 273–384. National Radiation Protection Board. ELF electromagnetic fields and the risk of cancer: report of an advisory group on non-ionizing radiation. Chilton, Didcot: Documents of the NRPB 12, 2001. Linet MS, Hatch EE, Kleinerman RA, et al. Residential exposure to magnetic fields and acute lymphoblastic leukemia in children. N Engl J Med 1997; 337: 1–7. McBride ML, Gallagher RP, Theriault G, et al. Power frequency electric and magnetic fields and risk of childhood leukemia in Canada. Am J Epidemiol 1999; 149: 831–42. UK Childhood Cancer Study Investigators. Exposure to power frequency magnetic fields and the risk of childhood cancer: a casecontrol study. Lancet 1999; 354: 1925–31. Ahlbom A, Day N, Feychting M, et al. A pooled analysis of magnetic fields and childhood leukaemia. Br J Cancer 2000: 83: 692–98. Greenland S, Sheppard AR, Kaune WT, et al. A pooled analysis of magnetic fields, wire codes, and childhood leukemia. Epidemiology 2000; 11: 624–34. Arbetarskyddsstyrelsen. Low frequency electric and magnetic fields. The precautionary principle for national authorities. ADI 477, Solna: Arbetarskyddsstyrelsen, Publikationsservice, 1996. National Institute of Environmental Health Sciences. NIEHS Report on health effects from exposure to power-line frequency electric and magnetic fields. Research Triangle Park: NIH publication No. 99–4493, 1999.
THE LANCET • Vol 357 • April 14, 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.
NASCET.6 Analysis of these data also showed that the benefit from surgery was greatest among patients aged over 75 (figure).7 The number of patients in this age-group was small, even with all trials combined, but the overall findings (a high risk of stroke without surgery, but no increase in operative risk) were similar in the two largest trials. Should symptomatic carotid disease therefore be investigated and treated more actively in the very elderly? This decision depends on the extent to which the trial results can be generalised to routine clinical practice. Since patients who enter RCTs are generally healthier than those who do not,8 and the endarterectomy trials also actively excluded patients with severe concurrent disease, the trial populations will not have been typical of routine clinical practice. However, this observation does not necessarily invalidate the findings. In patients 75 years and older the increased risk of stroke without surgery (figure) is consistent with findings from community-based incidence studies,9 and the acceptable operative risk is consistent with recent non-trial series.10–12 Although a systematic review of studies of the risk of stroke and death due to endarterectomy did report high risks in patients aged over 75 years compared with younger patients, the differences in absolute risk were only 1–2%.13 Even if the operative risk of stroke and death for very old people is as much as 10%, which is higher than is generally reported,10–13 endarterectomy would still be beneficial because of the high risk of stroke without surgery. Endarterectomy in routine clinical practice is therefore likely to benefit reasonably fit patients over 75 years old. However, the population has aged in the 15 years since the endarterectomy trials began recruitment, and continues to do so. In France, for example, the number of centenarians is about 8500, but will increase to 41 000 by 2025 and 150 000 by 2050.14 The clinical dilemma is now whether to operate on patients aged 85, 90, or even older.10–12 Not one of the 6092 patients in the CETC were over 90, and so treatment decisions in the very elderly currently have to be made without trial data. It is important, therefore, that RCTs in progress, such as local vs general anaesthetic for endarterectomy ([email protected]), endarterectomy vs medical treatment for asymptomatic carotid stenosis ([email protected]), and endarterectomy vs angioplasty and stenting ([email protected]) do recruit such very elderly patients. Finally, one justification for a less aggressive approach to disease prevention in the elderly has been that they will not survive long enough to benefit. However, this assumption does not stand up to scrutiny. The average life-expectancy at age 85 in the USA, for example, is 6 years. The reduction in stroke risk after endarterectomy for severe symptomatic carotid stenosis is evident within 6 months of surgery and peaks by 2 years.3,4 Most 85-year-olds would therefore survive long enough to benefit. Indeed, in some series, survival after endarterectomy is independent of age because of the high risk of cardiac death in young patients with severe arterial disease.11,12 Elderly patients commonly do not wish to undergo endarterectomy, but they should at least be given the choice. The trial evidence suggests that they are likely to benefit, and the operative risks reported are acceptable.10–13 It is therefore difficult to justify not investigating carotid disease in an otherwise fit elderly patient who is willing to consider surgery and who has an appropriate risk profile.15 Peter M Rothwell Department of Clinical Neurology, University of Oxford, Radcliffe Infirmary, Oxford OX2 6HE, UK (e-mail: [email protected])
THE LANCET • Vol 357 • April 14, 2001
1
2
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5 6
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8 9 10
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12 13
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Dunlop WE, Rosenblood L, Lawrason L, Birdsall L, Rusnack CH. Effects of age and severity of illness on outcome and length of stay in geriatric surgical patients. Am J Surg 1993; 165: 577–80. Burns-Cox N, Campbell WB, Van Nimmen BAJ, Vacaeren PMK, Lucarotti M. Surgical care and outcome for patients in their nineties. Br J Surg 1997; 84: 496–98. European Carotid Surgery Trialists’ Collaborative Group. Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet 1998; 351: 1379–87. North American Symptomatic Carotid Endarterectomy Trialists’ Collaborative Group. The final results of the NASCET trial. N Engl J Med 1998; 339: 1415–25. Oxman AD, Guyatt GH. A consumers guide to subgroup analysis. Ann Intern Med 1992; 116: 78–84. Rothwell PM, Gutnikov SA, Eliasziw M, et al for the Carotid Endarterectomy Trialists’ Collaboration. Meta-analysis of individual patient data from randomised controlled trials of carotid endarterectomy for symptomatic stenosis: (1) Patients and methods. Cerebrovasc Dis 2000; 10 (suppl 2): 77. Rothwell PM, Mayberg MR, Warlow CP, Barnett HJM for the Carotid Endarterectomy Trialists’ Collaboration. Meta-analysis of individual patient data from randomised controlled trials of carotid endarterectomy for symptomatic stenosis: (3) The efficacy of surgery in important pre-defined subgroups. Cerebrovasc Dis 2000; 10 (suppl 2): 108. Stiller CA. Centralised treatment, entry to trials and survival. Br J Cancer 1994; 70: 352–62. Bonita R. Epidemiology of stroke. Lancet 1992; 339: 342–47. Perler BA, Dardik A, Burleyson GP, Gordon TA, Williams GM. Influence of age and hospital volume on the results of carotid endarterectomy: a statewide analysis of 9918 cases. J Vasc Surg 1998; 27: 25–31. Van-Damme H, Lacroix H, Desiron Q, Nevelsteen A, Limet R, Suy R. Carotid surgery in octogenarians: is it worthwhile? Acta Chir Belg 1996; 96: 71–77. Thomas PC, Grigg M. Carotid surgery in the octogenarian. Aust N Z J Surg 1996; 66: 231–34. Rothwell PM, Slattery J, Warlow CP. A systematic review of clinical and angiographic predictors of stroke and death due to carotid endarterectomy. BMJ 1997; 315: 1571–77. Dinh QC. Projection de la population totale pour la France metropolitaine: Base RP90, Horizons 1990–2050. Demographie Societe No. 44, INSEE, 1995, Paris. Rothwell PM, Warlow CP on behalf of the ECST Collaborators. Prediction of benefit from carotid endarterectomy in individual patients: a risk-modelling study. Lancet 1999; 353: 2105–10.
Current thinking about risks from currents The production, transmission, distribution, and use of electricity generate electromagnetic fields having a frequency of 50–60 Hz, sometimes called power frequency. This range falls within the extremely lowfrequency band (ELF-EMF). The hypothesis that exposure to such fields increases the risk of cancer has been controversial ever since a link was reported more than two decades ago.1 The main reason for scepticism has been the low amount of energy that these fields transfer because of their low frequency; the wave-length corresponding to 50 Hz is similar to the radius of the earth. The only established mechanism for biological effects of ELF-EMF is induction of electrical currents in the tissue, but the fields to which a person is normally exposed in the environment are generally orders of magnitude too low to be of any significance in this context, in view of the endogenous electrical activity in nerve and muscle cells. These considerations have led physicists to claim that ELF-EMF cannot produce biological effects at the low levels of environmental exposure. Modern society is inconceivable without electricity, so exposure to ELF-EMF is ubiquitous, which is one reason why research on ELF-EMF and health risks has continued despite the limited biophysical plausibility. 1143
For personal use. Only reproduce with permission from The Lancet Publishing Group.
COMMENTARY
Another reason is that scientists have been intrigued by the hypothesis, and to no small extent by some of the findings. The research programmes have included cellular research, animal experiments, studies on human volunteers, and epidemiology. Despite much activity in all these scientific branches, the epidemiological findings have been the driving force because they have been more reproducible than the experimental findings, and because they have made it possible to gradually narrow down the area of interest. Last month the UK National Radiological Protection Board published a comprehensive evaluation of the scientific evidence on ELF-EMF and cancer.2 The report, by an expert group led by Sir Richard Doll, concludes: “Laboratory experiments have provided no good evidence that extremely low frequency electromagnetic fields are capable of producing cancer, nor do human epidemiological studies suggest that they cause cancer in general”. However, the group also writes: “Recent large and well-conducted studies have provided better evidence than was available in the past on the relationship between power frequency magnetic field exposure and the risk of cancer. Taken in conjunction they suggest that relatively heavy average exposure of 0·4 µT or more are associated with a doubling of the risk of leukaemia in children under 15 years of age. The evidence is, however, not conclusive”. The epidemiological studies that have been conducted during the past two decades have gradually improved and recent studies from the USA, Canada, and the UK have been particularly informative.3–5 The improvement has been especially true for exposure assessment: 20 years ago there were no instruments that could be used in epidemiological studies to assess magnetic fields over periods of time. Rather than making the original observation go away, the better studies have generally confirmed it as far as childhood leukaemia is concerned, at least according to the expert group. The group, however, makes the qualification that the evidence for an association is limited to fairly high exposures—in fact at levels so high that in the UK only 0·5% of the population is estimated to face such exposures.5 For other types of cancer that were also implicated in earlier research, such as brain tumours and leukaemia in adults, the expert group finds the evidence unconvincing. The expert group relies to some extent on two pooled analyses with similar results, one conducted by a group led by one of us.6,7 Both these used primary data from the studies pooled. Going back to primary data was essential mainly because it enabled analysis for exposure levels at which individual studies did not have sufficient numbers of subjects for meaningful analyses. In neither of these pooled analyses was there any evidence of an effect to speak of at exposures below 0·3–0·4 µT; above that level both pooled analyses showed clear effects. In our study the relative risk was 2·0 (95%CI 1·3–3·1) for exposures at or above 0·4 µT, an effect that is not likely to be explained by chance. The expert group also noted that we stratified the studies in our pooled analysis into two groups: one group was dominated by recent large studies with direct exposure assessments but with a potential for selection bias, whereas the other group consisted of smaller studies done perhaps with less refined methods for measuring exposure but with little or no potential for selection bias. The pooled results were virtually the same within these two strata. Thus, these two groups of studies mutually support each other’s findings. One cannot, however, exclude the possibility that the findings are due to 1144
selection bias in the first group of studies and random variation in the second group of studies. Therefore, the evidence for an effect of ELF-EMF on risk of childhood leukaemia remains unconvincing. The fundamental question of how magnetic fields would exert an effect on cancer risk is still unresolved, as the expert group notes. Large-animal studies have yielded negative results. In-vitro studies and studies in volunteers have perhaps shed glimmers of light—eg, with suggestions that calcium flux, gene expression, or melatonin production might be involved in the pathogenesis of the cancer. The reports, however, have been notoriously difficult for other laboratories to confirm, and there is still no strong candidate for a mechanism behind a possible ELF-EMF and cancer effect. So not only do the epidemiological results lack support from theoretical physics but also from experiments on cells, animals, and human volunteers. Yet the results remain. With childhood leukaemia having an incidence rate of 4/100 000 children per year and with fewer than 1% exposed, at least in the UK, few children would be affected. These small numbers in no way make the problem negligible. A thorough risk evaluation would require more data than is available, not only with respect to whether or not magnetic fields can produce cancer but, if so, also with respect to the nature of the doseresponse curve and the occurrence and distribution of the relevant exposure; the very high costs of reducing exposures (for example, from existing power lines) have to be factored in. If action has to be taken on data at hand perhaps the recommendations released by the Swedish government some years ago are worth revisiting.8 In essence they recommend that unnecessary heavy exposures be avoided if it is possible without excessive costs or technical difficulties. Such advice is not very different from the recommendations issued by the US National Institute for Environmental Health Sciences 2 years ago: “However, because everyone . . . is . . . exposed, . . . passive regulatory action is warranted”.9 *Anders Ahlbom, Maria Feychting Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden (e-mail: [email protected]) 1 2
3
4
5
6
7
8
9
Wertheimer N, Leeper E. Electrical wiring configurations and childhood cancer. Am J Epidemiol 1979; 109: 273–384. National Radiation Protection Board. ELF electromagnetic fields and the risk of cancer: report of an advisory group on non-ionizing radiation. Chilton, Didcot: Documents of the NRPB 12, 2001. Linet MS, Hatch EE, Kleinerman RA, et al. Residential exposure to magnetic fields and acute lymphoblastic leukemia in children. N Engl J Med 1997; 337: 1–7. McBride ML, Gallagher RP, Theriault G, et al. Power frequency electric and magnetic fields and risk of childhood leukemia in Canada. Am J Epidemiol 1999; 149: 831–42. UK Childhood Cancer Study Investigators. Exposure to power frequency magnetic fields and the risk of childhood cancer: a casecontrol study. Lancet 1999; 354: 1925–31. Ahlbom A, Day N, Feychting M, et al. A pooled analysis of magnetic fields and childhood leukaemia. Br J Cancer 2000: 83: 692–98. Greenland S, Sheppard AR, Kaune WT, et al. A pooled analysis of magnetic fields, wire codes, and childhood leukemia. Epidemiology 2000; 11: 624–34. Arbetarskyddsstyrelsen. Low frequency electric and magnetic fields. The precautionary principle for national authorities. ADI 477, Solna: Arbetarskyddsstyrelsen, Publikationsservice, 1996. National Institute of Environmental Health Sciences. NIEHS Report on health effects from exposure to power-line frequency electric and magnetic fields. Research Triangle Park: NIH publication No. 99–4493, 1999.
THE LANCET • Vol 357 • April 14, 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.