Possible Health Effects of Exposure to Residential Electric and Magnetic Fields (1997) / Chapter Skim
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5 Epidemiology
5 Epidemiology
Pages 117-190
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From page 117... ...
Based on an analysis of the epidemiologic literature, the committee makes the following general conclusions: · Wire codes t are associated with an approximate 1.5-fold excess of childhood leukemia, which is statistically significant. Although the literature is not entirely consistent, the combined results from the array of studies that have examined wire codes and related markers of exposure, such as proximity to power lines and calculated magnetic fields from power lines, indicate that an association is present.
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From page 118... ...
However, epidemiologic studies have generated little evidence that average magnetic fields account for the observed association between wire codes and childhood leukemia. Wire codes are not strong predictors of magnetic-field strengths in homes, although they do distinguish very high fields from outdoor wiring from lesser fields reasonably well.
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From page 119... ...
" In this chapter, published epidemiologic data are reviewed that bear upon the potential association between exposure to low-frequency 60-Hz residential magnetic fields and disease, the potential sources of random and systematic errors common to epidemiologic studies are explored, the possible confounding factors and their potential effects on the findings of the studies are examined, and the effect of these various factors on the conclusions derived from the epidemiologic work is evaluated. The consistency of the results are explored using methods of data pooling, and the criteria for causality will be discussed as they apply to the problem at hand.
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From page 120... ...
. An observed risk of 1.0 or 2.0 relating high wire codes to childhood leukemia might be indicative of a "true" risk in the neighborhood of 1.0 or 2.0, in the absence of other sources of error attributable to random processes.
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From page 121... ...
Exposure misclassification is a pervasive concern in epidemiologic studies on the effects of exposure to electric and magnetic fields. Errors can occur on several levels.
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From page 122... ...
In studies of residential magnetic-field exposure and childhood cancer, cases have typically constituted a complete roster of all diagnosed children in a specified geographic area and time period. The goal of control selection in such studies is to identify an unbiased sample from the population in that area for the corresponding time period to provide a baseline of exposure prevalence (e.g., prevalence of high-wire-code homes)
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From page 123... ...
If medical X-ray exposures caused an increased risk of childhood leukemia and the exposures were not accounted for in the analysis, electric-blanket use would be falsely implicated as being responsible for an increase in risk that actually would be due to X-ray exposure. The control of confounding is, in principle, easily achieved through statistical methods.
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From page 124... ...
, then unrecognized confounders are less likely to be responsible for the association. For large relative risks, confounders are presumed to be apparent and already identified as important risk factors.
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From page 125... ...
Lack of scientific evidence from other disciplines or conflicting information from other disciplines of course does not confirm that the epidemiologic studies are in error; the nonepidemiologic research, in itself, might be absent or flawed. Nonetheless, the interpretations of the data obtained in epidemiologic studies should be based in part on the agreement or disagreement of findings from other disciplines.
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From page 126... ...
Results of the epidemiologic studies are organized into tables that focus on childhood leukemia (Table A5-4) , childhood brain tumors (Table A5-5)
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From page 127... ...
If an association between some characteristic of the power lines (as captured by the "wire codes" defined for use in epidemiologic studies) and cancer exists, several factors might be responsible.
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From page 128... ...
In the next section, the strength of the evidence is considered in the following areas: The evidence linking wire codes to childhood cancer (path 1~; the evidence linking wire codes to potential confounders (path 2a) ; the evidence linking potential confounders to cancer (path 2b)
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From page 129... ...
Three sets of investigators have previously conducted meta-analyses of childhood cancer and residential exposure to magnetic fields. A report by Great Britain's Advisory Group on Non-ionizing Radiation of the National Radiation Protection Board summarized results of the childhood residential studies, providing pooled odds-ratio estimates for each exposure metric (NRPB 19921.
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From page 130... ...
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From page 132... ...
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From page 133... ...
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From page 134... ...
For data based on the distance from the source of electromagnetic fields and for measured magnetic fields, the pooled odds ratios were found to be increased, but not statistically significant. They concluded that in spite of the increased odds ratios, the small sample sizes (three for each estimate)
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From page 135... ...
For assessments in which multiple exposure metrics were explicitly stipulated, the committee's preferences for the use of exposure metrics to combine studies were in the following order: wire codes, distance from electric source, calculated magnetic fields, and spot measurements of magnetic fields. This order was chosen because wire codes were used in the initial study that identified an association with childhood leukemia.
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From page 136... ...
Similarly, one can combine the probability of rejecting the null hypothesis in individual studies to assess the sensitivity of the results to publication bias and determine the number of additional null studies needed to reduce a statistically significant combined effect to nonsignificance. This number is the so-called "fail-safe N." Statistics that incorporate the individual study effect sizes use either of two statistical models: fixed effects or random effects.
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From page 137... ...
Rather than provide all these data, two tables are presented that describe the data used in the analysis, two tables provide a sample of the results, and a single table summarizes the results of all the selection and exposure definitions in the studies considered. The full set of 16 studies of residential exposure and childhood cancer was considered earlier and is shown in Table A5-1.
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From page 140... ...
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From page 142... ...
Overall, seven studies were available; the results for the combination of LCC wire codes and 100-m distance cut points are shown in Table 5-3. All three combinations gave fairly similar results, showing statistically significantly increased odds ratios, moderate insensitivity to singlestudy deletions, and large fail-safe N's and sample sizes needed to balance the observed data, indicating substantial robustness of results from additional studies.
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From page 143... ...
reported calculations based on historical power use to estimate the magnetic fields in the nearby residences. Note that because proximity to power distribution lines is a key factor in the calculated historical magnetic fields, this method of estimating exposure shares features with wire codes and distance measurements.
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From page 144... ...
In the graph of the odds ratios (Figure 5-2) , the preponderance of positive associations across exposure metrics (except for spot magnetic-field measurements)
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From page 145... ...
In view of the strong interest in this topic among scientists, it seems unlikely that any investigator would have trouble getting even a negative study published. Indeed, 2 of the 12 published studies reported odds ratios less than 1.0, and 8 of 12 did not have p values less than or equal to 0.05 for any exposure cut points, suggesting that negative and nonsignificant results are readily publishable.
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From page 146... ...
Selection Bias and Control Selection in Residential Childhood Cancer Studies In the absence of any true association between wire codes and cancer, faulty methods of case or control selection in case-control studies can yield spurious associations. If, for some reason, controls in studies of childhood cancer and wire codes were consistently selected in a manner that underrepresented highwire-code residents, then those studies would consistently yield spuriously increased measurements of association.
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From page 147... ...
Specific aspects of the residential childhood cancer studies that might have led to bias (Tables 5-5 and 5-6) are considered here.
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From page 151... ...
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From page 152... ...
Although the case-selection process had minor variations, the methods of most of the studies would be expected to generate reasonably representative study groups. The age ranges varied among the studies; upper-age bounds for analyses of childhood cancers ranged from 10 to 20.
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From page 153... ...
Although the rationale of combining that method with random digit dialing was not provided by the study, it was partly due to logistic considerations in adding on to a previously conducted smaller case-control study. One of the problems in using friend controls is that they might be overmatched (Kelsey et al.
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From page 154... ...
(1993) argue that the observed associations between wire codes and childhood cancers in one study by Savitz et al.
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From page 155... ...
Rather, each possible bias might contribute in a small way to the odds ratio in each study, some tending to increase and some tending to decrease the value of the odds ratio determined. Because the study designs and methods are diverse and because no pervasive flaw is found in all of them, the committee believes that any particular selection bias is unlikely to completely explain the reported associations between exposure to magnetic fields, as reflected by the wire codes, and childhood cancer incidence.
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From page 156... ...
, wire codes were ascertained blindly (i.e., without knowledge of whether the home had been occupied by a case or a control) (Savitz et al.
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From page 157... ...
Selection Bias There are a number of important concerns about the manner in which controls were selected. These concerns have direct implications for the measurements of association, some being likely to produce bias toward spurious positive associations, such as selection of residentially stable controls who might tend to have lower wire codes (e.g., Savitz et al.
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From page 158... ...
These factors produce a likely connection between income level and socioeconomic status that could confound the effect of wire codes. Multifamily residences often have internal power-distribution wiring that can give rise to magnetic fields that cannot be captured conveniently
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From page 159... ...
Finally, the population movement out of central cities, with small yards and greater housing density, to suburban areas with greater average distance from power lines to residences, might result in reduced wire codes and reduced in-home exposures. Because older homes tend to fall into the high-wire-code category more often than new homes, confounding might be introduced if a real or imposed disparity exists between the ages of homes of cases and controls.
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From page 160... ...
To control for such confounding, the confounder must be identified, measured as one of the variables in the study, and accounted for in the statistical analysis. Candidate confounders should be a known or suspected risk factor for childhood leukemia, but the causes of childhood leukemia are generally not known.
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From page 161... ...
1991~. All the observed variations in the incidence rates make it difficult to interpret small risk ratios in epidemiologic studies.
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From page 162... ...
If income or socioeconomic status is suspected to be a confounder in a study of the association of wire codes and childhood leukemia, the study subjects can be stratified by income, and the association between wire code and risk of childhood leukemia can then be evaluated separately for each income group. If several potential confounders need to be evaluated, the more usual method of controlling for confounders is to apply regression procedures.
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From page 163... ...
Most epidemiologic studies examine several exposure metrics, and some studies have been reanalyzed with several metrics, so some inferences concerning the appropriateness of the different indicators might be possible. All indicators used, including wire codes and field measurements, are surrogates for some unknown "causal exposure" (if one is indeed present)
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From page 164... ...
If total accumulated exposure is of interest, a deficiency common to all the studies is the failure of the exposure metrics to incorporate away-from-home exposures, although some studies suggest that away-from-home exposure might not contribute much to total exposure (Kaune etal.
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From page 165... ...
Measured Magnetic Fields and Childhood Cancer The key issue that puzzles many who conduct and follow epidemiologic research is the so-called "wirecode paradox": If wire codes operate through magnetic fields, why are measured magnetic fields less strongly associated with cancer risk than the wire codes themselves? In other words, if wire codes are functioning as an indirect indicator of exposure, then why is the more direct indicator (measured magnetic fields)
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From page 166... ...
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From page 167... ...
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From page 168... ...
It is not known whether wire codes might be a better indicator than spot measurements of the average magnetic field over the space and time of interest in relationship to the development of childhood leukemia. Perhaps the most tenuous part of the paradox is the assumption that epidemiologic studies have obtained valid estimates of the association between measured fields and childhood cancer.
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From page 169... ...
The failure of 24-hr magnetic-field measurements to produce clearer associations with cancer than the spot measurements constitutes evidence against an association between magnetic fields and cancer. A significant anomaly in comparing the studies in Denver and Los Angeles is the notably consistent magnitude of relative risks for childhood leukemia based on wire codes in spite of what would appear to be different field strengths that correspond to those codes.
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From page 170... ...
Wire-(Uode (Uategories in Relation to Magnetic Fields and Cancer In examining the pattern of cancer risk in relation to the Wertheimer and Leeper (1979) wire codes, consideration should be given to whether the uneven relationship in field strength (see Appendix B)
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From page 171... ...
and more precise than those from the five-level wire code used in the 1988 study (Savitz and Kaune 19939. These increases in relative risks combined with improvements in accuracy of the modified wire codes as an indicator of residential magnetic-field strength lend some support to the hypothesis that magnetic fields might be associated with cancer.
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From page 172... ...
On the other hand, if validated indicators of exposure that are superior to residential wire codes do not yield stronger associations with childhood cancer, then the likelihood that magnetic fields per se cause cancer would be diminished. Improvements in assessments of magnetic-field exposure of children is under way, but close collaboration of engineers, biostatisticians, and epidemiologists is needed to ensure that the refinements are technically valid and applicable in field settings.
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From page 173... ...
A positive association must be subject to one of two categories of explanation: either the wire codes are related to childhood cancer through magnetic-field exposures or they are serving as an indicator of some other agent or process. To make this evaluation, both the evidence that the association results from magnetic fields and the evidence implicating something else must be considered.
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From page 174... ...
Approaching the question of confounders from both ends risk factors for childhood cancer or correlates with wire codes few contenders, other than magnetic fields, explain the association. Childhood-cancer correlates that remain under contention are viral exposure or some other phenomenon associated with housing density, which, in turn, is associated with wire codes.
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From page 175... ...
Clearly, more work is needed in assessing the implications of wire code on magnetic-field exposures and on other exposures. Consistency with Secular Trend Data The argument has been made that magnetic fields could not be a causative factor in childhood cancer because substantial increases in residential consumption of electricity (assumed to be linked to increases in personal magnetic-field exposures)
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From page 176... ...
In summary, large increases in the residential use of electricity clearly have not been accompanied by comparable increases in the incidence of childhood leukemia. The apparent persuasiveness of the argument based on the observation that magnetic-field exposures are not related to the incidence of childhood leukemia is diminished, however, by the large and indeterminate uncertainties in the implicit assumption that population exposures to magnetic fields increase proportionately to residential energy use.
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From page 177... ...
After testing for a number of appliances, prenatal exposures to electric blankets were reported to be associated with increased risk of brain cancer (odds ratio (OR)
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From page 178... ...
The authors concluded that this study "provides some indication that pre- and post-natal exposure to electric blankets may increase the risk of developing childhood cancer." The size of the study population, however, produced too low a power to detect anything but strong associations. In addition, the nature of the exposure assessment is insufficiently precise, which could introduce substantial but presumably random misclassification.
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From page 179... ...
, workers engaged in electrical occupations have often been found to have slightly increased risks of leukemia and brain cancer (Savitz and Ahlbom 1994~. The general structure of these studies is to identify one or more groups of electrical occupations, such as linemen, electricians, electric-equipment assemblers, and electrical engineers, and compare their cancer incidence or mortality rates to that of nonelectrical occupations.
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From page 180... ...
1994~. Brain cancer showed much more modest increases (relative risks of 1.5-2.8)
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From page 181... ...
There are a multiplicity of exposure sources of potential interest (including residential exposures from power lines, occupational exposures from videodisplay terminals (VDTs) , and other exposures from electric appliances, such as electric blankets)
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From page 182... ...
After adjustment for cigarette smoking, risk of early pregnancy loss was increased among women who resided in residences with measured fields above around 0.25 At, particularly above 0.63 AT. On the basis of 6-8 cases of exposure in the highest exposure strata and 2-3 controls, the odds ratios were found to be substantially increased (in the range of 3 to 5)
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From page 183... ...
Relative-risk estimates suggested no increase in risk, the odds ratios being 0.8, 0.7, and 0.9 for cleft palate, cleft lip, and neural tube defects, respectively, for electric-blanket use. Uncertainty arises from the reliance on self-reported electric-appliance use several years in the past and the potential bias from nonresponse.
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From page 184... ...
, whereas among women who worked with VDTs emitting the highest magnetic-field strength, the odds ratio rose to 3.4. Combining the number of hours of use with the estimated field strength produced by the unit yielded increased risks in relation to exposure to extremely-lowfrequency and very-low-frequency magnetic fields.
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From page 185... ...
Confounding is a somewhat greater concern for reproductive health outcomes than for childhood cancer, largely because so much more is known about risk factors. Across many reproductive outcomes (with the exception of many congenital malformations)
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From page 186... ...
, and, overall, case homes had statistically significantly higher measured magnetic-field exposures than control homes. As noted by the authors, the median magnetic field was measured at 0.04 AT, whereas that calculated in the study of Reichmanis et al.
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From page 187... ...
(1988) conducted a study in England among people living near 132-kV overhead power lines.
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From page 188... ...
conducted a telephone interview survey of 382 persons to assess the prevalence of depressive symptoms and headache in relation to visual proximity of residence to overhead power lines. They found a statistically significant positive association for depressive symptoms but not for headaches or migraines.
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From page 189... ...
(1988) reported more headaches and migraines among people living near 132-kV overhead power lines than among those in a comparison population living away from overhead lines.
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From page 190... ...
A range of symptoms for clinically relevant outcomes were reported in the studies, and only some of the studies used standardized instruments to assess their occurrence. Hospital and medical records are likely to result in incomplete ascertainment and are likely biased by educational level and socioeconomic status of the subject.
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