|
Subject:
Articolo integrale (English)
dello studio tedesco CEM-Leucemie
Residential magnetic fields as a risk factor for childhood acute leukaemia:
Results from a German population-based case-control study Joachim Schüz 1
*, Jan-Peter Grigat 2, Karl Brinkmann 2, Jörg Michaelis 11Institute for
Medical Statistics and Documentation, University of Mainz, Mainz, Germany
2Forschungsuerbund: EMV biologischer Systeme (Electromagnetic
Compatibility of Biological Systems), Technical University of Braunschweig,
Braunschweig, Germany
email: Joachim Schüz:
schuez@imsd.uni-mainz.de
*Correspondence to Joachim Schüz, Institut für Medizinische Statistik
und Dokumentation, Universität Mainz, D-55101 Mainz, Germany - Fax: +49 6131 172968
- setDOI("ADOI=10.1002/1097
0215(200002)9999:99993.0.CO;2-D")
Funded by: German Federal Ministry for the Environment, Nuclear Safety and
Nature Preservation
Keywordselectromagnetic fields; leukaemia; childhood cancer; case-control
study; epidemiology; environmental exposures AbstractOur objective was to
investigate whether exposure to residential power-frequency (50 Hz)
magnetic fields above 0.2 T increases a child's risk of leukaemia and to
confirm or reject a finding from a previous German study on this topic,
which reported increased leukaemia risk with exposure to stronger magnetic
fields during the night.
A population-based case-control study was used,
covering the whole of the former West Germany. Residential magnetic fields
were measured over 24 hr for 514 children with acute leukaemia identified
by the German Childhood Cancer Registry and 1,301 control children taken
from population registration files. Magnetic fields above 0.2 T were
relatively rare in Germany (only 1.5% of the study population). Childhood
leukaemia and 24 hr median magnetic fields were only weakly related (OR =
1.55, 95% CI 0.65-3.67). A significant association was
seen between childhood leukaemia and magnetic field exposure during the
night (OR = 3.21, 95% CI 1.33-7.80).
A dose-response-relationship was
observed after combining the data of all German studies on magnetic fields
and childhood leukaemia. The evidence for an association between childhood
leukaemia and magnetic field eposure in our study comes from a measure of
exposure during the night. Despite the large size of our study, the
results are based on small numbers of exposed children. If the observed
association stands, the effect on a population level in Germany would be
small. © 2001 Wiley-Liss, Inc.
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
Received: 21 July 2000; Revised: 25 September 2000; Accepted: 29 September
2000 -
Digital Object Identifier (DOI)
10.1002/1097-0215(200002)9999:9999<::AID-IJC1097>3.0.CO;2-D About
DOI
Article Text
During the last 2 decades, a number of epidemiological studies have
explored the association between childhood leukaemia and residential
exposure to power-frequency electromagnetic fields (EMFs). Although there
are
inconsistencies across studies, reviews have suggested that there is a
small excess leukaemia risk with magnetic field exposure above 0.2 T.[1-5]
Based on these findings and epidemiological studies that observed an
association between adult chronic lymphoblastic leukaemia and occupational
exposure to EMFs,[6] an international working group convened by the U.S.
National Institute of Environmental Health Sciences (NIEHS) rated exposure
to
power-frequency magnetic fields as possibly carcinogenic to humans using
the International Agency for Research on Cancer criteria for classifying
potential carcinogens.[4] However, so far, there is no convincing
supportive
laboratory evidence for this rating, and the absence of a plausible
biological mechanism of disease causation limits the evidence derived from
epidemiological studies.[4]
From 1993 to 1997 we performed 2 smaller EMF studies embedded in
population-based case-control studies carried out by the German Childhood
Cancer Registry (GCCR), one in the northwestern part of Germany (Lower
Saxony) and one in Berlin, and then pooled the 2 sets of results.[7][8]
Exposure was assessed by measurements of the magnetic field over 24 hr in
the child's bedroom. Based on 176 children with acute leukaemia and 414
control children, we observed an elevated odds ratio (OR) of 2.3 with a
wide 95 percent confidence interval (95% CI) of 0.8-6.7 due to the small
number of children exposed to median magnetic fields above 0.2 T (9 cases,
8
controls). When the analysis was restricted to the median magnetic field
measured during the night, the OR based on the 0.2 T cut-off point
increased to 3.8 (95% CI 1.2-11.9). The association was strongest for
children under the age of 5 years.
Because of these inconclusive results, we expanded the magnetic field
measurements to a large-scale population-based epidemiological study on a
variety of potential risk factors for childhood cancer covering the whole
of
the former West Germany, including densely populated areas like Hamburg,
the Ruhr district and Munich.[9][10]
Before we started conducting measurements, we set up defined hypotheses and planned an analysis
strategy that will be described in Material and Methods below. The primary
intentions of the extended study were (i) to contribute to the ongoing
discussion on this topic by achieving more stable estimates for the
leukaemia risk associated with average exposure to residential magnetic
fields under German conditions, (ii) to confirm or reject the results of
our previous studies regarding exposure during the night and (iii) to
explore whether adjustment for different confounding factors changes the
results.
MATERIAL AND METHODS
Briefly, our EMF study involved cases and controls participating in a
large-scale case-control study carried out between 1993 and 1997. The
study consisted of 2 parts: a nation-wide component (NW component)[9] and
one restricted to geographic areas around nuclear installations and
selected control regions (NI component).[10] Measurements of residential
magnetic fields started in November 1997 and continued until December
1999. Cases
were identified from the nation-wide GCCR Registry at the University of
Mainz, which has been estimated to be more than 95% complete.[11] Controls
were selected from complete files of local resident registration offices.
Study basis
The NW component of the case-control study comprised children with acute
leukaemia, non-Hodgkin's lymphoma and solid tumours. Cases were eligible
if one of these diseases was diagnosed when the child was younger than 15
years between October 1992 and September 1994 and if he or she lived in
the former West Germany on the date of diagnosis. The NI component was
embedded in an ecological study investigating childhood malignancies in
the vicinity of German nuclear installations. The study population
comprised cases with childhood acute leukaemia or non-Hodgkin's lymphoma
aged 15 years or less, born after 1 July 1975 and, on the date of
diagnosis, living in a nuclear installation area (i.e., at most, 15 km
away from a nuclear installation) or a matched control region. The
diagnostic period of the NI component was from January 1980 to September
1994, but cases diagnosed before January 1990 and their corresponding
controls were excluded from EMF measurements. This was done to avoid
extremely long time periods between the date of diagnosis and the date of
the measurement. Some cases who met the inclusion criteria of both
components were counted only once, in the analysis of the total sample.
For both components, one control matched by gender, date of birth and
community (smallest administrative unit in Germany) was selected for each
case. A list of 4 addresses of children of the same gender and with a
birth date as close as possible to a given date (the birth date of the
corresponding case but changed slightly to prevent identification by the
local resident registration office) was requested from the registration
office of the community in which the case lived on the date of diagnosis.
We randomly chose 1 control from this list. If the chosen family did not
participate, we contacted another family from the remaining names on the
list. We checked that no case family (who might have been sampled as a
potential control) was selected as a control.
For each control, the date of diagnosis of the corresponding case was
defined as the reference date (both date of diagnosis and reference date
will be referred to as reference date hereafter). Information on potential
risk factors was collected by both self-administered questionnaire and
subsequent telephone interview. During this interview, we asked for all
addresses where the child lived between the birth date and the reference
date.
The EMF study, which started after completion of the original case-control
study, comprised only cases with acute leukaemia. Since we adopted a
frequency-matched design for the EMF study,[12][13] all controls were
eligible, even if they were originally matched to a case with a
non-Hodgkin's lymphoma or a solid tumour. To avoid overlap with our
previous German EMF studies in Lower Saxony and Berlin, children whose
families had already participated in these studies were excluded from the
current study.
This concerned children of the NW component who lived in West Berlin at
the date of diagnosis (they partially formed the study basis of our
previous EMF study in Berlin[8]), children of the NW component who had a
reference date before July 1993 and lived in Lower Saxony at the date of
diagnosis and children living in the vicinity of a nuclear installation
located in Lower Saxony.[7] For the following reasons, participants in the
original study were also excluded from the EMF study: the reference date
was before 1 January 1990, the residence where the child lived longest
before the reference date was out of Germany or the parents refused to
give former addresses during the telephone interview.
Measurements
Measurements over 24 hr were conducted at 2 fixed locations, one under the
mattress of the child's bed and one in the living room at a place removed
from any electrical appliance. In the child's bedroom, the Physical
Systems
FW2a (Physical Systems, Inc., Bradenton, FL) field meter was used to
record magnetic field intensity at 50 Hz.
The EMDEX II (Enertech, Campbell,
CA) field meter, calibrated at 50 Hz with a response to frequencies
ranging from
40 to 800 Hz, was used in the living room; this additional measurement was
made for quality purposes.
To obtain information on the spatial
distribution of the magnetic field, the field technicians performed
short-term measurements with the EMDEX II connected to a measurement
wheel,
recording a value approximately every 30 cm while walking very slowly
through all rooms of the residence. Moreover, the field technicians
determined if there were any power lines, transformers or substations
located near the residence.
Spot measurements were conducted to identify sources of elevated magnetic
fields. We used them as 1 of 3 exposure variables in our previous
studies;
but since we observed a poor agreement between 24 hr measurements and spot
measurements[14] and childhood leukaemia was not related to spot
measurements in our former[8] and in other[4] studies, they were not used
to estimate exposure in the current study.
Magnetic field intensity was recorded in 3 dimensions, from which we
calculated the root mean square (often called the resultant) magnitude at
50 Hz. For analytical purposes, we calculated arithmetic and geometric
means,
SDs and several percentiles (including the median) of each measurement
over 24 hr. The median during the night (night-time value) was calculated
from the data recorded between 10 PM and 6 AM; the daytime median was
based on data acquired between 6 AM and 10 PM.
According to the design of the previous German EMF studies,[7][8] the
address where the child lived longest before the reference date was used
for measurements. If more than 1 residence fulfilled this criterion, e.g.,
if a 2-year-old child lived in 2 different residences over a period of 1
year, we performed measurements in all relevant dwellings.
Multiple
measurements for 1 participant were later combined to a single data record
by calculating the means of the measurement parameters. All measurements
were conducted by field technicians from the Forschungsverbund.
The
engineers were blinded to case or control status; however, sometimes it
might have been obvious that the child was a case.
Statistical analysis
As in our previous studies, the median of the 24 hr measurement in the
child's bedroom was defined as a proxy for the child's average exposure to
magnetic fields. To compare our results with those from studies in the
United States,[15][16] Canada,[17] New Zealand[18] and the United
Kingdom,[19]
we also calculated ORs using the arithmetic mean of the measurement. The
second parameter for confirmatory analysis was the night-time value, as
described above.
The cut-off point to discriminate between exposed and
non-exposed subjects was 0.2 T.
To explore a possible dose-response relationship, we defined 4 categories with cut-off points at 0.1, 0.2 and
0.4 T.
ORs and 95% CIs were computed with logistic regression models using the
PHREG procedure of SAS (Cary, NC) software, release 6.12. According the
frequency-matched design of the EMF study, data were stratified for
gender,
age (age groups of 1 year) and year of birth. All analyses were
additionally adjusted for socio-economic status (high, other), which was
estimated on the basis of family net income and level of parental
education.
A few families,
particularly parents of controls, refused to give their income; therefore,
socio-economic status was estimated on the basis of the parental
occupational history. Frequency-matched analyses were also adjusted for
degree of urbanisation (urban, mixed, rural) to compensate for ignoring
the matching for community in the original case-control study and for
study component (NI component only, NW component or both). Further
potential confounders considered in additional analyses were residential
mobility (0, 1, 2 moves between birth date and date of diagnosis), season
of measurement, type of residence (single-family homes/farms,
double-family homes/row-houses, apartment buildings with 3 to 10 parties,
apartment buildings >10 parties) and monthly family net income (5
levels). These factors were related to the occurrence of elevated magnetic
fields in earlier studies.[4][20]
RESULTS
According to the eligibility criteria, the EMF study population comprised
847 cases and 2,127 controls (Table I). Sixty-four cases and 86 controls
were excluded since the residence where they lived longest before the
reference date was not known or was out of Germany. Of 2,935 addresses
relevant for measurements (there were 108 subjects with 2 relevant
residences and 1 subject with 4 relevant residences), families in 1,853
residences participated (63.1%). Reasons for non-participation were
refusal (18.6%), no appointment with the family could be made (14.1%;
i.e., the family had no phone and did not respond to letters, the family
did not speak German, the new owner or tenant of the residence could not
be traced, the address was not complete or wrong) or the building was
pulled down or renovated and improved (4.2%). Because the family of the
study participant had moved, 949 residences (32.3%) were inhabited by new
owners or tenants (hereafter called new tenants). There were no
differences between case and control families; however, there were large
differences regarding participation: of 1,986 families still living in the
relevant residence, 1,479 participated (74.5%), but only 356 of 949 new
tenants (37.5%) approved the measurement.
Eighteen measurements were not
included in the analysis because of erroneous recordings, i.e.,
malfunctions of the measurement instrument, the instrument was
inadvertently placed too close to an electrical appliance or the family
agreed to only short-term measurements.
In all, exposure information was available for 514 cases and 1,301
controls (Table I). Table I. Response Rate Among Current Occupants1
Contacted Regarding Measurements of Residential Magnetic Field
---------------------------------
Residences of cases
---------------------------------
Residences of controls
---------------------------------
n%%n%%
---------------------------------
Eligible847100.0 2,127100.0 Residential history unknown20 22 Lived longest
out of Germany44 64 Contacted78392.4100.02,04196.0100.0 No measurement
could be conducted263 722 Participated52061.466.41,31962.064.6
Erroneous recordings4 14 Measurement at wrong address2 4 Included in
analysis51460.7 1,30161.2
---------------------------------
1 Study participant's family still lived in 67.7% of all relevant
residences.
Table II gives the distribution of cases and controls by gender, age
socio-economic status, monthly family net income, degree of urbanisation,
type of residence, residential mobility and study component. Differences
in age and study component distribution were expected and were due to the
study design since we included matched partners of cases with solid
tumours (all children with a solid tumour were participants of the NW
component and, on average, were older at date of diagnosis than leukaemia
cases).[9]
Differences between cases and controls were also observed with respect to
socio-economic status.
This was due to a higher response of controls with
high socio-economic status than controls with other socio-economic status.
Hence, all analyses were adjusted for that factor. Despite the strong
association with family net income, case or control status was only
moderately associated with type of residence. Table II. Distribution of
Cases and Controls by Gender, Age, Socio-Economic Status, Monthly Family
Net Income, Degree of Urbanisation, Type of Residence, Residential
Mobility and Study Component
---------------------------------
Cases (n = 514)Controls (n = 1301)p
---------------------------------
Gender Male304 (59.1%)779 (59.9%) Female210 (40.9%)522 (40.1%)0.77Age
(years)
0-4290 (56.4%)635 (48.8%) 5-9153 (29.8%)401 (30.8%) 10+71 (13.8%)265
(20.4%)<0.01Socio-economic status Other374 (72.8%)880 (67.6%) High140
(27.2%)421 (32.4%)0.03Monthly family net income <1,000 Euro21 (4.2%)43
(3.5%) 1,000-2,000 Euro299 (59.9%)584 (47.9%) 2,000-3,000 Euro134
(26.9%)420 (34.5%) >3,000 Euro45 (9.0%)171 (14.0%)<0.01 Unknown1583
Degree of urbanisation Urban174 (33.9%)489 (37.6%) Mixed188 (36.6%)440
(33.8%) Rural152 (29.6%)372 (28.6%)0.31Type of residence Single family
houses/farms222 (43.2%)563 (43.3%) Duplexes/row-houses134 (26.1%)403
(31.0%) Small apartment buildings (3-10 units)132 (25.7%)285 (21.9%) Large
apartment buildings (>10 units)26 (5.1%)50 (3.8%)0.09Number of
residences (residential mobility) 1344 (66.9%)895 (68.8%) 2-3163
(31.7%)384 (29.5%) >37 (1.4%)22 (1.7%)0.60Study part NW component360
(70.0%)1,086 (83.5%) NI component78 (15.2%)115 (8.8%) Both components76
(14.8%)100 (7.7%)<0.01
---------------------------------
Table III gives the results of our primary analyses. As described in
Material and Methods, our confirmatory hypothesis focused on the median
magnetic field of the 24 hr measurement in the child's bedroom and on the
night-time value.
While the association between childhood leukaemia and
magnetic fields was weak on the basis of median magnetic fields, it was
pronounced based on exposure at night. The difference between night-time
and day-time exposures became more marked after incorporating both
magnetic field characteristics in the same logistic regression model; at
0.2 T, the OR for night-time exposure increased to 3.69 (95% CI
1.32-10.3), while the OR for daytime decreased to 0.77 (95% CI 0.29-2.03).
As can also be seen from Table III, the prevalence of magnetic fields
exceeding 0.2 T in Germany was very low, and only 27 subjects (1.5%) were
exposed to average magnetic fields above this value [24 subjects (1.3%)
during the night]. Only 8 (29%) of these 27 median magnetic fields above
0.2 T were produced by high-voltage transmission lines.[14] Table III. OR
for Childhood Acute Leukaemia by Exposure to Residential Magnetic Fields
(MFs,
Primary Analysis)
---------------------------------
<0.2 T0.2 T<0.1 T0.1 to <0.2 T0.2 to <0.4 T0.4 T
---------------------------------
Median MF1 Cases50594723363 Controls1,283181,21073153 Adjusted OR (95%
CI)21.001.55 (0.65-3.67)1.001.15 (0.73-1.81)1.16 (0.43-3.11)5.81
(0.78-43.2) p value 0.32 0.540.770.09 p value for 2-tailed test for trend
0.34Arithmetic mean MF1 Cases5001445644113 Controls1,277241,18889213
Adjusted OR (95% CI)21.001.69
(0.83-3.46)1.001.34 (0.90-2.01)1.45 (0.67-3.14)5.94 (0.80-44.1) p value
0.15 0.150.350.08 p value for 2-tailed test for trend 0.07Daytime value3
Cases504104644073 Controls1,279221,19683184 Adjusted OR (95% CI)21.001.35
(0.60-3.07)1.001.32 (0.87-2.02)1.10 (0.43-2.78)3.44 (0.59-20.2) p value
0.47 0.190.850.17 p value for 2-tailed test for trend 0.28Night-time
value4 Cases502124683475 Controls1,289121,2197084 Adjusted OR (95%
CI)21.003.21 (1.33-7.80)1.001.42 (0.90-2.23)2.53 (0.86-7.46)5.53
(1.15-26.6) p value 0.01 0.130.090.03 p value for 2-tailed test for trend
0.01
---------------------------------
1 Derived from 24 hr measurement in the child's bedroom in the residence
where the child lived longest before the reference date.
2 OR and respective 95% CI from logistic regression analyses stratified
for year of birth, age groups of 1 year and gender and additionally
adjusted for degree of urbanisation (urban, mixed, rural), study component
(NI component only, NW component only or both) and socio-economic status
(high, other).
3 Median magnetic field between 6 AM and 10 PM derived from the 24 hr
measurement in the child's bedroom.
4 Median magnetic field between 10 PM and 6 AM derived from the 24 hr
measurement in the child's bedroom.
Adjustment for other potential confounding factors had only a small effect
on ORs. After including the season of measurement, residential mobility
and type of residence in the logistic regression models, the ORs were
slightly lower; however, the statistically significant association between
childhood leukaemia and exposure during the night remained. The respective
ORs are shown in Table IV. When we restricted the analysis to children who
lived in a single home between date of birth and reference date
(including
a few who lived for the entire reference period in homes for which we
conducted 24 hr measurements), the association was even more pronounced
(Table IV). When we examined the data for children aged 4 years or younger and
children aged 5 years or older, we observed a pattern similar to that in
our previous EMF studies: the risk was highest for younger children (Table
IV).[8] The Ors restricted to the major morphological subgroup of
leukaemia, acute lymphoblastic leukaemia (ALL), are shown in Table IV,
allowing comparison with studies that involved only cases with ALL. Table
IV. Additional
Analysis Involving Potential Confounding Factors on Subsets of Data
(Exploratory Analysis)
---------------------------------
<0.2 T0.2 T<0.1 T0.1 to <0.2 T0.2 to <0.4 T0.4 T
---------------------------------
Additional potential confounding factors Median MF1 Cases50594723363
Controls1,283181,21073153 Adjusted OR (95% CI)21.001.49
(0.62-3.55)1.001.16 (0.73-1.83)1.12 (0.41-3.04)5.26 (0.69-40.2) p value
0.37 0.520.830.11 Night-time value3 Cases502124683475
Controls1,289121,2197084 Adjusted OR (95% CI)21.003.21
(1.31-7.84)1.001.44 (0.92-2.28)2.58 (0.87-7.70)5.33 (1.09-26.0) p value
0.01 0.110.090.04Analysis restricted to children with a single residence
Median MF1 Cases34363202342 Controls8911384249112 Adjusted OR (95%
CI)41.001.59 (0.55-4.59)1.001.23 (0.71-2.14)1.06 (0.32-3.56)11.6
(0.83-160) p value 0.39 0.450.920.07 Night-time value3 Cases339103162373
Controls89688494762 Adjusted OR (95% CI)41.004.35 (1.49-12.8)1.001.60
(0.91-2.81)3.07 (0.93-10.1)15.6 (1.35-182) p value 0.01
0.100.070.03Analysis restricted to children aged 4 or younger Median MF1
Cases28552652032 Controls62965943551 Adjusted OR (95% CI)41.002.10
(0.59-7.40)1.001.30 (0.72-2.35)1.21 (0.28-5.26)12.7 (0.92-174) p value
0.25 0.380.800.06 Night-time value3 Cases28372622143 Controls63146013031
Adjusted OR (95% CI)41.004.48 (1.20-16.7)1.001.74 (0.95-3.19)2.75
(0.60-12.7)14.9 (1.20-185) p value 0.03 0.070.190.04Analysis restricted to
cases with ALL Median MF1 Cases44394172663
Controls1,283181,21073153 Adjusted OR (95% CI)41.001.81
(0.76-4.34)1.001.04 (0.64-1.70)1.36 (0.50-3.69)6.24 (0.85-45.8) p value
0.18 0.870.550.07 Night-time value3 Cases441114113065
Controls1,289121,2197084 Adjusted OR (95% CI)41.003.36 (1.35-8.37)1.001.48
(0.92-2.39)2.49 (0.80-7.73)6.19 (1.29-29.7) p value 0.01
0.110.110.02Primary analysis excluding children with Down syndrome Median
MF1 Cases49774663143 Controls1,282181,20973153 Adjusted OR (95%
CI)41.001.25 (0.49-3.19)1.001.09 (0.68-1.73)0.80 (0.26-2.51)5.99
(0.81-44.2) p value 0.65 0.720.700.08 Night-time value3 Cases494104623255
Controls1,288121,2187084 Adjusted OR (95% CI)41.002.75 (1.09-6.96)1.001.36
(0.86-2.15)1.85 (0.57-6.07)5.63 (1.17-27.0) p value 0.03 0.190.310.03
---------------------------------
1 Derived from the 24 hr measurement in the child's bedroom in the
residence where the child lived longest before the reference date. MF,
magnetic field.
2 OR and respective 95% CI from logistic regression analyses stratified
for year of birth, age groups of 1 year and gender and additionally
adjusted for degree of urbanisation (urban, mixed, rural), study component
(NI component only, NW component only or both) and socio-economic status
(high, other) and for residential mobility (1 residence, 2 to 3
residences,
more than 3 residences), season of measurement (summer, autumn/spring,
winter) and type of residence (single family/farms, duplexes/row-houses,
small apartment buildings, large apartment buildings).
3 Median magnetic field between 10 PM and 6 AM derived from 24 hr
measurement in the child's bedroom.
4 OR and respective 95% CI from logistic regression analyses stratified
for year of birth, age groups of 1 year and gender and additionally
adjusted for degree of urbanisation (urban, mixed, rural) and
socio-economic status (high, other).
Ten cases and 1 control with Down syndrome participated in our EMF study,
and 2 of the cases had daytime as well as night-time exposures above 0.2
T.
Excluding these children from the study, like Linet et al.[16] did in the
U.S. study, led to lower and less precise risk estimates (Table IV). Both
exposed cases with Down syndrome had median and night-time magnetic fields
ranging from 0.2 to 0.25 T.
Table V gives the results for the combined risk estimates after pooling
the current study with our previous EMF studies in Lower Saxony and
Berlin.[7][8] The logistic regression model involved the former East and
West Germany as an additional independent variable and study setting (Berlin,
Lower Saxony, NI component only, NW component only or both) as a further
dummy variable for adjustment. All combined analyses included children
with Down syndrome.
The methods for exposure assessment were similar for
all 3 studies, except that we used the FW2 field meter in the current
study while the EMDEX II was used in the former studies. As can be seen in
Table V, the leukaemia risk was statistically significant for median
magnetic fields of 0.4 T and above. For the night-time value, we observed
a clear dose-reponse relationship (2-tailed p for trend < 0.01).
Nevertheless, this has to be interpreted with care since the pooled
analyses combined the current replication study with the
hypothesis-generating studies. Table V. Pooled OR for Childhood Acute
Leukaemia by Exposure to Residential Magnetic Fields (MF)1
---------------------------------
<0.2 T0.2 T<0.1 T0.1 to <0.2 T0.2 to <0.4 T0.4 T
---------------------------------
Median MF2 Cases6721862943117 Controls1,689261,59594215 Adjusted OR (95%
CI)31.001.58 (0.83-3.03)1.001.08 (0.73-1.61)1.19 (0.55-2.57)3.53
(1.01-12.3) p value 0.16 0.690.670.05Arithmetic mean MF2
Cases6672360661176 Controls1,678371,560118325 Adjusted OR (95%
CI)31.001.51 (0.86-2.65)1.001.28 (0.90-1.80)1.33 (0.71-2.50)3.02
(0.82-11.2) p value 0.15 0.160.370.10Night-time value4 Cases 6692162544147
Controls1,698171,60791125 Adjusted OR (95% CI)21.002.80
(1.42-5.52)1.001.33 (0.90-1.97)2.40 (1.07-5.37)4.28 (1.25-14.7) p value
<0.01 0.150.030.02
---------------------------------
1 Pooled analysis of current study and our 2 previous German studies.[7][8]-
2 Derived from 24 hr measurement in the child's bedroom in the residence
where the child lived longest before the reference date.
3 OR and respective 95% CI from logistic regression analyses stratified
for year of birth, age groups of 1 year and gender and additionally
adjusted for degree of urbanisation (urban, mixed, rural), socio-economic
status (high, other), part of Germany (West and West Berlin, East Berlin)
and study setting (Lower Saxony, Berlin, NI component only, NW component
only or both).
4 Median magnetic field between 10 PM and 6 AM derived from 24 hr
measurement in the child's bedroom.
DISCUSSION
Strengths and limitations
One strength of our study is that it was population-based because cases
were identified from an almost complete nation-wide cancer registry and
controls were drawn at random from complete files of population registries.
Since in
Germany registration is compulsory for all residents, these files provide
an excellent sampling frame for epidemiological studies. Furthermore, our
study was embedded in a large-scale case-control study on a variety of
risk factors for childhood cancer; therefore, we had very detailed
information on potential confounding factors. Our comprehensive method for
measuring magnetic fields enabled us to identify the source of elevated
magnetic fields and to compare those measured in the child's bedroom to
those obtained in other rooms of the dwelling. The large study population
was another strength of the study, but in hindsight, it was not large
enough under German conditions of environmental exposure to EMF.
When we calculated the sample size of the study, we assumed a prevalence
of magnetic fields above 0.2 T of about 3%, which seemed reasonable based
on our previous studies in Lower Saxony and Berlin and further measurement
activities by the Forschungsverbund.[21] However, the observed prevalence
among the control group was only 1.4% (95% CI 0.7-2.0%),[14] higher than
in rural Lower Saxony (0.9%) but considerably lower than in Berlin
(5.8%).[8]
It was more than 5 times lower than in the North American studies[15-17]
and slightly lower than in the UK study,[19] for which the prevalence was
2%.
From a statistical point of view, the unexpectedly low prevalence
decreased the statistical power of our study and, hence, limited the
precision of our risk estimates. From a public health perspective, however,
it means that even if the association between childhood leukaemia and
residential magnetic fields stands, only few German children would be
affected.
Besides the low number of residences with average magnetic fields
exceeding 0.2 T, our study has 2 major drawbacks. One is the relatively
low response rate. About 65% of all families approved the measurement.
There were no differences between cases and controls; however, the
population of our EMF study was already a subset of a case-control study
that had response rates of 84% among cases eligible for the EMF study and
67% among controls.
Therefore, bias introduced by non-participation cannot be ruled out. A few
studies have addressed the problem of selection bias in EMF
investigations.[4][22][23] They demonstrated that elevated risks may, to
some extent, be due to differences between the case and control groups
regarding socio-economic status, but this did not explain the observed
association entirely. In our EMF study, socio-economic status was only
moderately associated with the occurrence of magnetic fields above 0.2 T.
In Germany, this may be due to the fact that, although stronger magnetic
fields occur more often in apartment buildings, only in urban areas was
the type of residence associated with family income.
We found a somewhat
stronger association between 5-level monthly family net income and
magnetic fields, with higher magnetic fields for the lowest income
category.[14] However, of 4 families among this income category for which
we obtained stronger magnetic fields, there were 1 case and 3 controls.
Another
noticeable finding was that after we combined the data of all German EMF
studies and calculated risk estimates separately for high as well as other
socio-economic status, the respective ORs were 1.53 (95% CI 0.39-6.00,
high) and 1.67 (95% CI 0.78-3.56, other) for the median of the 24 hr
measurement and 3.89 (95% CI 0.88-17.2, high) and 3.00 (95% CI 1.34-6.70,
other) for the night-time value. Hence, the risk estimates were similar
for both strata of socio-economic status; however, they were less precise
for subjects with higher socio-economic status.
In conclusion, selection
bias remains a concern; however, we found no evidence that it explains our
findings.
Another limitation of our study is the long time lag between the
aetiologically relevant time period and the measurement period. Due to
oeconomical reasons, we decided to await the results of the 2 smaller
studies[8] before we expanded the EMF research. While the reference dates
of the current study were between 1990 and 1994, it was late 1997 when we
started the measurements. Moreover, we assessed exposure in the residence
where the child lived longest before the reference date; because some
families had moved before the reference date, for some subjects the time
lag was >10 years. For 50.3% of subjects, the time lag was <5 years
(cases 50.6%, controls 50.2%). We tried to compensate this weakness, at
least partially, by carrying out very comprehensive measurements. To avoid
falsely classifying subjects as positive, we identified the source that
produced the stronger magnetic field and considered the stability of the
measured values over time during an expert meeting. For some exposed
subjects, particularly those exposed to stronger magnetic fields produced
by indoor sources, measurements were repeated in December 1999 (and all
stronger magnetic fields were confirmed). Furthermore, we aimed at
reducing the number of false-negative subjects by excluding renovated and
improved buildings and a few residences where proximate power lines had
been removed. Exposure misclassification cannot be excluded, but it is
likely to be independent of case or control status (non-differential
misclassification) and, therefore, to dilute an effect instead of creating
a spurious one.[24] However, due to the small number of exposed subjects
in our study, this cannot be taken for granted: if we assume that only a
handful of subjects were misclassified, then, even if the
misclassification probability is equal for cases and controls, it could
have happened by chance that more cases than controls were falsely
classified as exposed, which leads to a spurious association; but this is
rather speculative. Our overall risk estimates were confirmed by ORs
calculated for the subset of subjects who lived in a single residence.
In conclusion, we acknowledge the limitation of the long time lag between
the aetiologically relevant time period and the measurement period;
however, it is unclear if and how this affected our findings.
Down syndrome is associated with an increased risk of developing childhood
leukaemia and is considered as being causal.[25] The relative risk is
high, around 30-fold,[26] and was even higher in our own study,[27] which
may be an indication not to include this high-risk group in EMF studies.
Children with Down syndrome were excluded from the EMF study of the
National Cancer Institute[16] but not from other studies.[4][15][18][19]
Two of 9 exposed
cases in our study were children with Down syndrome. Both had the common
B-cell precursor form of ALL (cALL); they were 1 and 6 years old on the
date of diagnosis. As shown in Table IV, exclusion of children with Down
syndrome led to substantially lower ORs for median magnetic fields between
0.1 and 0.4 T. The OR for median magnetic fields above 0.4 T, however, was
only marginally altered, and we still observed a conspicuous association
between childhood leukaemia and magnetic field exposure during the night.
Despite the high risk, not all children with Down syndrome develop a
haematological malignancy, and the causal pathway from the genetic
disorder to the first clinically evident symptoms of acute leukaemia is
not entirely understood.[28] Hence, exposure to magnetic fields as a
potential post-natal promotional effect cannot be excluded. In conclusion,
the observation that 2 of 9 exposed leukaemia cases were children with
Down syndrome was unexpected; however, we think that arguments to exclude
them from the analyses are not convincing.
Interpretation of results
Our study provides evidence for a weak association between childhood
leukaemia and exposure to residential power-frequency magnetic fields. An
explanation for this association remains unclear. The role of chance, bias
and confounding has been stressed again and again,[3][4] and in our study
an impact of these factors cannot be ruled out and no one of them alone
can explain our findings. Our finding for average exposure to residential
magnetic fields goes along with earlier studies on this topic that
conducted long-term magnetic field measurements and lies within the
confidence boundaries of the 3 large studies in the United States,[16]
Canada[17] and the United Kingdom (although for the latter no effect was
observed).[19] As in our previous studies,[8] the association was
strongest for younger children, a finding that was also seen in a Canadian
study.[29] Our risk estimates also correspond very well with those of a
pooled analysis by Ahlbom et al.,[20] who reported ORs of 1.08, 1.11 and
2.00 for exposure categories 0.1 to <0.2, 0.2 to <0.4 and 0.4 T,
respectively. The respective combined ORs from pooled analysis of all 3
German studies (Table V) are 1.08, 1.19 and 3.53.
Our attention was particularly drawn to our finding that the association
between childhood leukaemia and magnetic field exposure at night was
consistently stronger than the association between childhood leukaemia and
average magnetic field exposure. Four possible explanations came to mind;
it was a chance finding, it was due to some kind of bias, it resulted from
the use of an exposure measure that reflected the child's individual
exposure to magnetic fields more appropriately or it was aetiologically
relevant.
We explored leukaemia risk and exposure to magnetic fields at night in 2
earlier studies,[7][8] and a major aim of this third study was to test
this rather new hypothesis. Although our study confirmed our previous
findings, even in our pooled analysis only 38 subjects were exposed to
night-time magnetic fields above 0.2 T. Thus, the CIs of our risk
estimates are relatively wide. Nevertheless, our study consists of 4 parts,
which were carried out in different, partially overlapping German regions
and for different, partially overlapping diagnostic periods but showed
consistently that the strongest associations were observed for exposure to
magnetic fields at night. Thus, it appears that chance is an unlikely
explanation; but admittedly, this is only one study with few exposed
subjects. The investigators of the U.S. study[16] considered night-time
exposure to be an alternative exposure measure.[30] For the median
magnetic field during the night, they reported an OR of 1.50 (95% CI
0.94-2.74, 90-100th percentile
compared to the 0-49th percentile). The respective figure for the median
over 24 hr was 1.28 (95% CI 0.81-2.05). With that, the association between
leukaemia and magnetic fields became stronger after restricting the
relevant exposure to the night-time period; however, the association from
the U.S. study was weaker than the association from the combined German
studies.
As described above, particularly non-participation might have biased the
results. This is an overall concern but an unlikely explanation for our
consistent finding that the link between leukaemia and magnetic fields was
stronger when only exposure at night was taken into account. In all, 16
cases and 15 controls were exposed to magnetic fields above 0.2 T on
average as well as during the night; only 2 cases but 11 controls were
exposed on average but not at night; while 5 cases and 2 controls were
exposed only at night. This pattern was consistent for all study parts.
The limitations of different methods for exposure assessment in this field
have been thoroughly discussed.[4] A weakness of the measurements is that
they were conducted stationary within the residence at 1 point in time,
which is after the date of diagnosis, but were used to estimate the
subject's individual past exposure.
Exposure at night is probably the most
appropriate measurement because misclassification is reduced, exposure
being recorded when the child is there with the instruments. During
night-time, stationary measurements and personal dosimetry do not differ;
in both cases, the instrument is located near the child's bed.
Finally, our finding of an excess leukaemia risk with magnetic field
exposure during the night might be of aetiological relevance. It has been
hypothesized that exposure to higher magnetic fields suppresses the
nocturnal production and release of the hormone melatonin, which is
assumed to have oncostatic capabilities;[31][32] however, the melatonin
hypothesis has been proposed for breast cancer and hormone-dependent
cancers rather than leukaemia.[33][34] Nevertheless, young children have
higher melatonin levels than adults;[35] therefore, effects caused by
reduced melatonin concentrations might be more marked. So far, there is
weak supportive evidence for the melatonin hypothesis from human
laboratory studies.[4]
It might also be of aetiological relevance that 2 of our exposed children
with leukaemia had a known pre-natal genetic abnormality. Wiemels et al.[36]
reported that childhood ALL is frequently initiated by a chromosomal
translocation event in utero but a secondary post-natal event is required
for full leukaemogenesis.
Environmental exposures might provoke or promote
evolution of the pre-leukaemic clone.[37] Exposure to magnetic fields
might belong to these post-natal events.
Conclusions
The main outcomes of our EMF study are as follows: (i) in Germany, average
magnetic fields above 0.2 T are rare, so even if the association between
magnetic field exposure and childhood leukaemia should stand, the effect
on a population level would be relatively small; (ii) fewer than one-third
of all stronger magnetic fields were caused by high-voltage powerlines,
meaning that only a minor fraction of potentially magnetic field-related
leukaemia cases would be attributable to powerlines; (iii) we found no
convincing confounding factor that could explain the observed association;
and (iv) although our study shows an association between childhood
leukaemia and exposure to residential magnetic fields, it is neither a
proof nor a breakthrough.
The evidence for an association between childhood leukaemia and magnetic
fields in our study comes from a measure of the child's exposure during
the night. With the current study, we confirm the findings of our previous
studies.
Despite the large size of our study, risk estimates were
imprecise since only few subjects were exposed to magnetic fields
exceeding 0.2 T at night. Since other studies have measured magnetic
fields over 24 hr, there are further opportunities to explore the
association between childhood leukaemia and magnetic field exposure at
night.
Acknowledgements
We thank the following engineers who were involved in the planning and
conduction of the measurements: Mr B. Störmer, Mr A. Rüther, Mr M.
Menger (Lower Saxony study) and Dr E. Zemann (Berlin study). Ms Ilona
Kerenyi did a great job in managing the data exchange between the
technical centre and the epidemiological centre. We also thank the
following researchers who were involved in the conduct of the original
case-control studies: Drs P.
Kaatsch, U. Kaletsch, R. Meinert and G. Rippin, who checked the analysis
programs. We thank Dr J. Brix (Federal Office for Radiation Protection),
who scrutinised the conduct of the study on behalf of the German Federal
Ministry for the Environment, Nuclear Safety and Nature Preservation. Both
the epidemiological and the measurement parts of the study were funded
totally by the German Federal Ministry for the Environment, Nuclear Safety
and Nature Preservation. We especially thank all families included in the
study.
References
1Angelillo IF, Villari P. Residential exposure to
electromagnetic fields and childhood leukaemia: a meta-analysis. Bull
World Health Organ 1999;77: 906
15.print_JCIT("TYPE=JCIT&BIBID=BIB1&SNM=Angelillo&FNM=IF&SNM=Villari&FNM
=P&ATL=Residential exposure to electromagnetic fields and childhood
leukaemia: a meta-analysis&JTL=Bull World Health Organ&PYR=1999&VID=77&PPF=906&PPL=15")
Links2Greenland S, Sheppard AR, Kaune
WT, Poole C, Kelsh MA. A pooled analysis of magnetic fields, wire codes
and childhood leukemia. Epidemiology 2000;11: 624-34.print_JCIT("TYPE=JCIT&BIBID=BIB2&SNM=Greenland&FNM=S&SNM=Sheppard&FNM
=AR&SNM=Kaune&FNM=WT&SNM=Poole&FNM=C&SNM=Kelsh&FNM=MA&ATL=A
pooled analysis of magnetic fields, wire codes and childhood leukemia&JTL=Epidemiology&PYR=2000&VID=11&PPF=624&PPL=34")
Links3Meinert R, Michaelis J. Meta-analyses of studies on the association
between electromagnetic fields and childhood cancer. Radiat Environ
Biophys 1996;35: 11
8.print_JCIT("TYPE=JCIT&BIBID=BIB3&SNM=Meinert&FNM=R&SNM=Michaelis&FNM=J&
ATL=Meta-analyses of studies on the association between electromagnetic
fields and childhood cancer&JTL=Radiat Environ
Biophys&PYR=1996&VID=35&PPF=11&PPL=8") Links4Portier
CJ , Wolfe MS (eds).
National Institute of Environmental Health Sciences Working Group Report.
Assessment of health effects from exposure to power-line frequency
electric
and magnetic fields. NIH Publ 98-3981. Research Triangle Park, NC: NIEHS,
1998.print_BKCIT("TYPE=BKCIT&BIBID=BIB4&ED=Portier&ED=Wolfe&BTL=Assessment
of health effects from exposure to power-line frequency electric and
magnetic fields&PUB=NIEHS&PYR=1998") 5Repacholi MH,
Greenebaum B.
Interaction of static and extremely low frequency electric and magnetic
fields with living systems: health effects and research needs.
Bioelectromagnetics 1999;20:
133-60.print_JCIT("TYPE=JCIT&BIBID=BIB5&SNM=Repacholi&FNM=MH&SNM=Greenebaum&
FNM=B&ATL=Interaction of static and extremely low frequency electric
and
magnetic fields with living systems: health effects and research
needs&JTL=Bioelectromagnetics&PYR=1999&VID=20&PPF=133&PPL=60")
Links6Kheifets LI, Afifi AA, Buffler PA, Zhang ZW, Matkin CC. Occupational
electric and magnetic field exposure and leukemia. J Occup Environ Health
1997;39:
1074-91.print_JCIT("TYPE=JCIT&BIBID=BIB6&SNM=Kheifets&FNM=LI&SNM=Afifi&FNM=A
A&SNM=Buffler&FNM=PA&SNM=Zhang&FNM=ZW&SNM=Matkin&FNM=CC&ATL=Occupational
electric and magnetic field exposure and leukemia&JTL=J Occup Environ
Health&PYR=1997&VID=39&PPF=1074&PPL=91")
Links7Michaelis J, Schüz J, Meinert
R, Menger M, Grigat JP, Kaatsch P, et al. Childhood leukemia and
electromagnetic fields: results of a population-based case control study
in
Germany. Cancer Causes Control 1997;8:
167-74.print_JCIT("TYPE=JCIT&BIBID=BIB7&SNM=Michaelis&FNM=J&SNM=Schüz&FNM=J&
SNM=Meinert&FNM=R&SNM=Menger&FNM=M&SNM=Grigat&FNM=JP&SNM=Kaatsch&FNM=P&ATL=Childhood leukemia and electromagnetic fields: results of a
population-based
case control study in Germany&JTL=Cancer Causes
Control&PYR=1997&VID=8&PPF=167&PPL=74")
Links8Michaelis J, Schüz J, Meinert
R, Zemann E, Grigat JP, Kaatsch P, et al. Combined risk estimates for two
German population-based case-control studies on residential magnetic
fields
and childhood acute leukemia. Epidemiology 1998;9:
92-4.print_JCIT("TYPE=JCIT&BIBID=BIB8&SNM=Michaelis&FNM=J&SNM=Schüz&FNM=J&SN
M=Meinert&FNM=R&SNM=Zemann&FNM=E&SNM=Grigat&FNM=JP&SNM=Kaatsch&FNM=P&ATL=Combined risk estimates for two German population-based case-control studies
on
residential magnetic fields and childhood acute
leukemia&JTL=Epidemiology&PYR=1998&VID=9&PPF=92&PPL=4")
Links9Kaatsch P,
Kaletsch U, Meinert R, Miesner A, Hoisl M, Schüz J, et al. German case
control study on childhood leukemia - basic considerations, methodology
and
summary of the results. Klin Padiatr 1998;210:
185-91.print_JCIT("TYPE=JCIT&BIBID=BIB9&SNM=Kaatsch&FNM=P&SNM=Kaletsch&FNM=U
&SNM=Meinert&FNM=R&SNM=Miesner&FNM=A&SNM=Hoisl&FNM=M&SNM=Schüz&FNM=J&ATL=German case control study on childhood leukemia - basic considerations,
methodology and summary of the results&JTL=Klin
Padiatr&PYR=1998&VID=210&PPF=185&PPL=91")
Links10Kaatsch P, Kaletsch U,
Meinert R, Michaelis J. An extended study on childhood malignancies in the
vicinity of German nuclear power plants. Cancer Causes Control 1998;9:
529-33.print_JCIT("TYPE=JCIT&BIBID=BIB10&SNM=Kaatsch&FNM=P&SNM=Kaletsch&FNM=
U&SNM=Meinert&FNM=R&SNM=Michaelis&FNM=J&ATL=An
extended study on childhood
malignancies in the vicinity of German nuclear power plants&JTL=Cancer
Causes Control&PYR=1998&VID=9&PPF=529&PPL=33")
Links11Kaatsch P, Haaf G,
Michaelis J. Childhood malignancies in Germany - methods and results of a
nationwide registry. Eur J Cancer 1995;31A:
993-9.print_JCIT("TYPE=JCIT&BIBID=BIB11&SNM=Kaatsch&FNM=P&SNM=Haaf&FNM=G&SNM
=Michaelis&FNM=J&ATL=Childhood malignancies in Germany - methods
and results
of a nationwide registry&JTL=Eur J
Cancer&PYR=1995&VID=31A&PPF=993&PPL=9")
Links12Brookmeyer R, Liang KY, Linet M. Matched case-control designs and
overmatched analyses. Am J Epidemiol 1986;124:
693-701.print_JCIT("TYPE=JCIT&BIBID=BIB12&SNM=Brookmeyer&FNM=R&SNM=Liang&FNM
=KY&SNM=Linet&FNM=M&ATL=Matched case-control designs and
overmatched
analyses&JTL=Am J
Epidemiol&PYR=1986&VID=124&PPF=693&PPL=701")
Links13Neuhäuser M, Becher H. Improved odds ratio estimation by post hoc
stratification of case-control data. Stat Med 1997;16:
993-1004.print_JCIT("TYPE=JCIT&BIBID=BIB13&SNM=Neuhäuser&FNM=M&SNM=Becher&FN
M=H&ATL=Improved odds ratio estimation by post hoc stratification of
case-control data&JTL=Stat
Med&PYR=1997&VID=16&PPF=993&PPL=1004")
Links14Schüz J, Griget JP, Störmer B, Rippin G, Brinkmann K, Michaelis
J.
Extremely-low-frequency magnetic fields in residences in Germany:
distribution of measurements, comparison of two methods for assessing
exposure, and predictors for the occurrence of magnetic fields above
background level. Radiat Environ Biophys 2000;39:
233-40.print_JCIT("TYPE=JCIT&BIBID=BIB14&SNM=Schüz&FNM=J&SNM=Griget&FNM=JP&S
NM=Störmer&FNM=B&SNM=Rippin&FNM=G&SNM=Brinkmann&FNM=K&SNM=Michaelis&FNM=J&AT
L=Extremely-low-frequency magnetic fields in residences in Germany:
distribution of measurements, comparison of two methods for assessing
exposure, and predictors for the occurrence of magnetic fields above
background level&JTL=Radiat Environ
Biophys&PYR=2000&VID=39&PPF=233&PPL=40")
Links15London SJ, Thomas DC, Bowman JD, Sobel E, Cheng TC, Peters JM, et
al.
Exposure to residential electric and magnetic fields and risk of childhood
leukemia. Am J Epidemiol 1991;134:
923-37.print_JCIT("TYPE=JCIT&BIBID=BIB15&SNM=London&FNM=SJ&SNM=Thomas&FNM=DC
&SNM=Bowman&FNM=JD&SNM=Sobel&FNM=E&SNM=Cheng&FNM=TC&SNM=Peters&FNM=JM&ATL=Ex
posure to residential electric and magnetic fields and risk of childhood
leukemia&JTL=Am J
Epidemiol&PYR=1991&VID=134&PPF=923&PPL=37")
Links16Linet
MS, Hatch EE, Kleinerman RA, Robison LL, Kaune WT, Friedman DR, et al.
Residential exposure to magnetic fields and acute lymphoblastic leukemia
in
children. N Engl J Med 1997;337:
1-7.print_JCIT("TYPE=JCIT&BIBID=BIB16&SNM=Linet&FNM=MS&SNM=Hatch&FNM=EE&SNM=
Kleinerman&FNM=RA&SNM=Robison&FNM=LL&SNM=Kaune&FNM=WT&SNM=Friedman&FNM=DR&AT
L=Residential exposure to magnetic fields and acute lymphoblastic leukemia
in children&JTL=N Engl J
Med&PYR=1997&VID=337&PPF=1&PPL=7") Links17McBride
ML, Gallagher RP, Theriault G, Armstrong BG, Tamaro S, Spinelli JJ, et al.
Power-frequency electric and magnetic fields and risk of childhood
leukemia
in Canada. Am J Epidemiol 1999;149:
831-42.print_JCIT("TYPE=JCIT&BIBID=BIB17&SNM=McBride&FNM=ML&SNM=Gallagher&FN
M=RP&SNM=Theriault&FNM=G&SNM=Armstrong&FNM=BG&SNM=Tamaro&FNM=S&SNM=Spinelli&
FNM=JJ&ATL=Power-frequency electric and magnetic fields and risk of
childhood leukemia in Canada&JTL=Am J
Epidemiol&PYR=1999&VID=149&PPF=831&PPL=42")
Links18Dockerty JD, Elwood JM,
Skegg DC, Herbison GP. Electromagnetic field exposures and childhood
cancers
in New Zealand. Cancer Causes Control 1998;9:
299-300.print_JCIT("TYPE=JCIT&BIBID=BIB18&SNM=Dockerty&FNM=JD&SNM=Elwood&FNM
=JM&SNM=Skegg&FNM=DC&SNM=Herbison&FNM=GP&ATL=Electromagnetic
field exposures
and childhood cancers in New Zealand&JTL=Cancer Causes
Control&PYR=1998&VID=9&PPF=299&PPL=300") Links19UK
Childhood Cancer Study
Investigators. Exposure to power-frequency magnetic fields and the risk of
childhood cancer. Lancet 1999;354:
1925-31.print_JCIT("TYPE=JCIT&BIBID=BIB19&ATL=Exposure to
power-frequency
magnetic fields and the risk of childhood
cancer&JTL=Lancet&PYR=1999&VID=354&PPF=1925&PPL=31")
Links20Ahlbom A, Day N,
Feychting M, Roman E, Skinner J, Dockerty J, et al. A pooled analysis of
magnetic fields and childhood leukemia. Br J Cancer 2000;83:
692-8.print_JCIT("TYPE=JCIT&BIBID=BIB20&SNM=Ahlbom&FNM=A&SNM=Day&FNM=N&SNM=F
eychting&FNM=M&SNM=Roman&FNM=E&SNM=Skinner&FNM=J&SNM=Dockerty&FNM=J&ATL=A
pooled analysis of magnetic fields and childhood leukemia&JTL=Br JCancer&PYR=2000&VID=83&PPF=692&PPL=8") Links21Stamm
A, Zemann E.
Low-frequency magnetic fields: exposure assessment for epidemiological
studies. In: Brinkmann K , Kärner H , Schaefer H . Electromagnetic
compatibility of biological systems, vol. 4. Berlin: vde-Verlag
(1995).print_BKCIT("TYPE=BKCIT&BIBID=BIB21&SNM=Stamm&FNM=A&SNM=Zemann&FNM=E&
ED=Brinkmann&ED=Kärner&ED=Schaefer&BSERTL=Electromagnetic
compatibility of
biological systems&VID=4&PUB=vde-Verlag&PYR=1995")
22Gurney JG, Davis S,Schwartz SM, Mueller BA, Kaune WT, Stevens RG, et al. Childhood cancer
occurrence in relation to power line configurations: a study of potential
selection bias in case-control studies. Epidemiology 1995;6:
31-5.print_JCIT("TYPE=JCIT&BIBID=BIB22&SNM=Gurney&FNM=JG&SNM=Davis&FNM=S&SNM
=Schwartz&FNM=SM&SNM=Mueller&FNM=BA&SNM=Kaune&FNM=WT&SNM=Stevens&FNM=RG&ATL=
Childhood cancer occurrence in relation to power line configurations: a
study of potential selection bias in case-control
studies&JTL=Epidemiology&PYR=1995&VID=6&PPF=31&PPL=5")
Links23Hatch EE,
Kleinerman RA, Linet MS, Tarone RE, Kaune WT, Auvinen A, et al. Do
confounding or selection factors of residential wiring codes and magnetic
fields distort findings of EMF studies? Epidemiology 2000;11:
189-98.print_JCIT("TYPE=JCIT&BIBID=BIB23&SNM=Hatch&FNM=EE&SNM=Kleinerman&FNM
=RA&SNM=Linet&FNM=MS&SNM=Tarone&FNM=RE&SNM=Kaune&FNM=WT&SNM=Auvinen&FNM=A&AT
L=Do confounding or selection factors of residential wiring codes and
magnetic fields distort findings of EMF
studies?&JTL=Epidemiology&PYR=2000&VID=11&PPF=189&PPL=98")
Links24Breslow
NE, Day NE. Statistical methods in cancer research. The analysis of
case-control studies. IARC Sci Publ 32. Lyon: IARC,
1980.print_BKCIT("TYPE=BKCIT&BIBID=BIB24&SNM=Breslow&FNM=NE&SNM=Day&FNM=NE&B
TL=Statistical methods in cancer research. The analysis of case-control
studies&PUB=IARC&PYR=1980") 25Pui C. Childhood leukemias. N
Engl J Med
1995;332:
1618-30.print_JCIT("TYPE=JCIT&BIBID=BIB25&SNM=Pui&FNM=C&ATL=Childhood
leukemias&JTL=N Engl J
Med&PYR=1995&VID=332&PPF=1618&PPL=30") Links26Little
J. Epidemiology of childhood cancer. IARC Sci Publ 149. Lyon: IARC,
1999.print_BKCIT("TYPE=BKCIT&BIBID=BIB26&SNM=Little&FNM=J&BTL=Epidemiology
of childhood cancer&PUB=IARC&PYR=1999") 27Schüz J, Kaatsch
P, Kaletsch U,
Meinert R, Michaelis J. Association of childhood cancer with factors
related
to pregnancy and birth. Int J Epidemiol 1999;28:
631-9.print_JCIT("TYPE=JCIT&BIBID=BIB27&SNM=Schüz&FNM=J&SNM=Kaatsch&FNM=P&SN
M=Kaletsch&FNM=U&SNM=Meinert&FNM=R&SNM=Michaelis&FNM=J&ATL=Association
of
childhood cancer with factors related to pregnancy and birth&JTL=Int J
Epidemiol&PYR=1999&VID=28&PPF=631&PPL=9") Links28Shen
JJ, Williams BJ,
Zipursky A, Doyle J, Sherman SL, Jacobs PA, et al. Cytogenetic and
molecular
studies of Down syndrome individuals with leukemia. Am J Hum Genet
1995;56:
915-25.print_JCI("TYPE=JCIT&BIBID=BIB28&SNM=Shen&FNM=JJ&SNM=Williams&FNM=BJ
&SNM=Zipursky&FNM=A&SNM=Doyle&FNM=J&SNM=Sherman&FNM=SL&SNM=Jacobs&FNM=PA&ATL
=Cytogenetic and molecular studies of Down syndrome individuals with
leukemia&JTL=Am J Hum
Genet&PYR=1995&VID=56&PPF=915&PPL=25") Links29Green
LM, Miller AB, Agnew DA, Greenberg ML, Li J, Villeneuve PJ, et al.
Childhood
leukemia and personal monitoring of residential exposures to electric and
magnetic fields in Ontario, Canada. Cancer Causes Control 1999;10:
233-43.print_JCIT("TYPE=JCIT&BIBID=BIB29&SNM=Green&FNM=LM&SNM=Miller&FNM=AB&
SNM=Agnew&FNM=DA&SNM=Greenberg&FNM=ML&SNM=Li&FNM=J&SNM=Villeneuve&FNM=PJ&ATL
=Childhood leukemia and personal monitoring of residential exposures to
electric and magnetic fields in Ontario, Canada&JTL=Cancer Causes
Control&PYR=1999&VID=10&PPF=233&PPL=43")
Links30Auvinen A, Linet MS, Hatch
EE, Kleinerman RA, Robison LL, Kaune WT, et al. Extremely low-frequency
magnetic fields and childhood acute lymphoblastic leukemia: an exploratory
analysis of alternative exposure metrics. Am J Epidemiol 2000;152:
20-31.print_JCIT("TYPE=JCIT&BIBID=BIB30&SNM=Auvinen&FNM=A&SNM=Linet&FNM=MS&S
NM=Hatch&FNM=EE&SNM=Kleinerman&FNM=RA&SNM=Robison&FNM=LL&SNM=Kaune&FNM=WT&AT
L=Extremely low-frequency magnetic fields and childhood acute
lymphoblastic
leukemia: an exploratory analysis of alternative exposure
metrics&JTL=Am J
Epidemiol&PYR=2000&VID=152&PPF=20&PPL=31")
Links31Reiter RJ. Antioxidant
actions of melatonin. Adv Pharmacol 1997;38:
103-17.print_JCIT("TYPE=JCIT&BIBID=BIB31&SNM=Reiter&FNM=RJ&ATL=Antioxidant
actions of melatonin&JTL=Adv
Pharmacol&PYR=1997&VID=38&PPF=103&PPL=17")
Links32Reiter RJ. Reported biological consequences related to the
suppression of melatonin by electric and magnetic field exposure. Integr
Physiol Behav Sci 1995;30:
314-30.print_JCIT("TYPE=JCIT&BIBID=BIB32&SNM=Reiter&FNM=RJ&ATL=Reported
biological consequences related to the suppression of melatonin by
electric
and magnetic field exposure&JTL=Integr Physiol Behav
Sci&PYR=1995&VID=30&PPF=314&PPL=30") Links33Stevens
RG. Electric power use
and breast cancer: a hypothesis. Am J Epidemiol 1987;125:
556-61.print_JCIT("TYPE=JCIT&BIBID=BIB33&SNM=Stevens&FNM=RG&ATL=Electric
power use and breast cancer: a hypothesis&JTL=Am J
Epidemiol&PYR=1987&VID=125&PPF=556&PPL=61")
Links34Baldwin WS, Barrett JC.
Melatonin: receptor-mediated events that may affect breast and other
steroid
hormone-dependent cancers. Mol Carcinog 1998;21:
149-55.print_JCIT("TYPE=JCIT&BIBID=BIB34&SNM=Baldwin&FNM=WS&SNM=Barrett&FNM=
JC&ATL=Melatonin: receptor-mediated events that may affect breast and
other
steroid hormone-dependent cancers&JTL=Mol
Carcinog&PYR=1998&VID=21&PPF=149&PPL=55")
Links35Brzezinski A. Melatonin in
humans. N Engl J Med 1997;336:
186-95.print_JCIT("TYPE=JCIT&BIBID=BIB35&SNM=Brzezinski&FNM=A&ATL=Melatonin
in humans&JTL=N Engl J
Med&PYR=1997&VID=336&PPF=186&PPL=95") Links36Wiemels
JL, Cazzaniga G, Daniotti M, Eden OB, Addison GM, Masera G, et al.
Prenatal
origin of acute lymphoblastic leukaemia in children. Lancet 1999;354:
1499-503.print_JCIT("TYPE=JCIT&BIBID=BIB36&SNM=Wiemels&FNM=JL&SNM=Cazzaniga&
FNM=G&SNM=Daniotti&FNM=M&SNM=Eden&FNM=OB&SNM=Addison&FNM=GM&SNM=Masera&FNM=G
&ATL=Prenatal origin of acute lymphoblastic leukaemia in children&JTL=Lancet&PYR=1999&VID=354&PPF=1499&PPL=503")
Links37Greaves M.
Molecular genetics, natural history and the demise of childhood leukaemia.
Eur J Cancer 1999;35:
173-85.print_JCIT("TYPE=JCIT&BIBID=BIB37&SNM=Greaves&FNM=M&ATL=Molecular
genetics, natural history and the demise of childhood
leukaemia&JTL=Eur J
Cancer&PYR=1999&VID=35&PPF=173&PPL=85")
Links
FORUM ELETTROSMOG NAZIONALE
http://it.egroups.com/group/forum-campi-em
Visitate il sito AREA ELETTROSMOG:
http://www.verdinrete.it/ondakiller/
Per leggere i messaggi precedenti:
http://it.egroups.com/messages/forum-campi-em
|
"Questo sito
WEB vi informa"
Non siamo
responsabili della correttezza e/o della solvibilità
degli inserzionisti del ns. Network
Webmaster
- Copyright © 1998, Publisher Bamico ltd - All rights reserved
Tutti i diritti riservati - Vietata
la copia anche parziale dei contenuti, se non viene citata la fonte |
|
|
