Int. J. Cancer: 1220, 721–726 (2008)' 2007 Wiley-Liss, Inc.

FAST TRACK
Leukaemia in young children living in the vicinity of German nuclear
power plants
Peter Kaatsch*, Claudia Spix, Renate Schulze-Rath, Sven Schmiedel and Maria Blettner
Institute for Medical Biostatistics, Epidemiology and Informatics, German Childhood Cancer Registry,
Obere Zahlbacher Strasse 69, 55131 Mainz, Germany
A case control study was conducted where cases were children
younger than 5 years (diseased between 1980 and 2003) registeredat the german childhood cancer registry (GCCR). Populationbased matched controls (1:3) were selected from the corresponding registrar’s ofﬁce. Residential proximity to the nearest nuclear
power plant was determined for each subject individually (with a
precision of about 25 m). The report is focused on leukaemia andmainly on cases in the inner 5-km zone around the plants. The
study includes 593 leukaemia cases and 1,766 matched controls.
All leukaemia combined show a statistically signiﬁcant trend for
1/distance with a positive regression coefﬁcient of 1.75 [lower
95%-conﬁdence limit (CL): 0.65]; for acute lymphoid leukaemia
1.63 (lower 95%-CL: 0.39), for acute non-lymphocytic leukaemia
1.99 (lower 95%-CL: 20.41). This indicates a negative trend for
distance. Cases live closer to nuclear power plants than the randomly selected controls. A categorical analysis shows a statisticallysigniﬁcant odds ratio of 2.19 (lower 95%-CL: 1.51) for residential
proximity within 5 km compared to residence outside this area.
This result is largely attributed to cases in previous studies of the
GCCR (especially in the inner zone) as there is clearly some overlap between those studies. The result was not to be expected undercurrent radiation-epidemiological knowledge. Considering that
there is no evidence of relevant accidents and that possible confounders could not be identiﬁed, the observed positive distancetrend remains unexplained.
' 2007 Wiley-Liss, Inc.
Key words: childhood; leukaemia; nuclear power plants; populationbased; cancer registry

To date, the aetiology of childhood leukaemia has remainedinconclusive even though numerous epidemiological studies
have addressed this question. There are some risk factors discussed as possibly causal or protective include lifestyle, genetic
disposition, course of pregnancy and perinatal development, theimmune system and environmental hazards.1–5 One generally
accepted risk factor for leukaemia is exposure to ionising radiation.6,7 Whether there is a threshold level at which any higher
level of exposure will be associated with occurrence of leukaemias, however, is subject to controversy. Internationally, currently used estimates of cancerogenic radiation effects in the
low-dose range are based on linear no-threshold extrapolation;
regarding leukaemia, a quadratic model is also applicable.8,9Other authors work on the assumption that these models overestimate the effects in a dose range of <10 milli Sievert considerably.10 Child-speciﬁc conclusions are either not given in thesepublished reports or data are reported to be insufﬁcient for any
conclusions to be drawn.8
For many years, there has been controversy over whether or not
the emission of ionising radiation during routine operation of nuclear plants will already increase the risk of leukaemia in children.
Such an effect is not too likely as present-day emissions of ionising radiation from nuclear power plants in routine operation areseveral magnitudes lower than the value of 0.3 milli Sievert/year
not to be exceeded according to the guidelines for the operation of
nuclear power plants.11,12
In 1987 and 1989, British studies reported a statistically signiﬁcant increased rate of leukaemia in under 15-year-olds within a
10-mile zone of nuclear plants in England and Wales.13,14 These
Publication of the International Union Against Cancer

reports prompted a study of almost identical design that was basedon the data of the German Childhood Cancer Registry (GCCR)
and was conducted in the late 1980s. This was an ecological study
comparing disease rates within 15 km (roughly 10 miles) of German nuclear plants with those seen in speciﬁed control areas. The
study period extended from 1980 through 1990 (Study 1). An
increased rate of all cancer or, more speciﬁcally, leukaemia inchildren younger than 15 years within a 15-km zone of West German nuclear plants was not conﬁrmed. However, exploratory analyses indicated that, for example, in children younger than 5 years
living within the inner 5-km zone, the increase in leukaemia rate
was statistically signiﬁcant.15 As these results gave rise to controversial discussion and as at the same time a statistically signiﬁcantleukaemia cluster was seen near the North German nuclear power
plant of Kr€
ummel,16 the study period was extended to cover theyears 1991 through 1995 (Study 2).
Study 2 failed to reproduce statistically signiﬁcant results
regarding the subgroup for which results were signiﬁcantly
increased in the exploratory analysis of Study 1. Nevertheless, atendency was seen towards an increased relative risk (RR) for leukaemia to occur in under 5-year-olds within the 5-km vicinity.17
Even after these results had been published, discussions on apotential relationship between the occurrence of childhood leukaemia and close proximity to nuclear plants in routine operation
have not ceased. For this reason, a case control study was initiatedby the Federal government and started at the GCCR in 2003. In
this investigation, residential proximity to the nearest nuclear
power plant was determined for each subject individually. Thiscase control study was limited to children younger than 5 years.
As in Studies 1 and 2, not only leukaemia, but all childhood
malignancies were included. Its scope extends well beyond the
15-km zone deﬁned in the ﬁrst 2 studies.18 Some features regarding the design of all 3 GCCR studies are given in Table I.
The present report is focused on leukaemia and mainly on caseswith place of residence in the inner 5-km zone around the nuclear
power plants. Other results are published elsewhere.19 As in mostradiation-epidemiological studies, the leukaemia cases are subdivided for analysis into acute lymphoid and acute non-lymphocytic
leukaemias. Considering that some leukaemia cases of the previous studies (Studies 1 and 2), and especially those from the innerzone, are identical with those included in the recent study, anddata are thus not independent, this aspect will be given particularattention.
Abbreviations: CL, conﬁdence limit; GCCR, German Childhood Cancer
Registry; GPOH, German Society of Paediatric Oncology and Haematology; ICCC, International Classiﬁcation of Childhood Cancer; NPP, nuclear
power plants; OR, odds ratio; RR, relative risk.
Grant sponsors: Federal Ministry of the Environment, Nature Conservation and Nuclear Safety via the Federal Ofﬁce for Radiation Protection;
Grant number: StSch 4334.
*Correspondence to: Institute for Medical Biostatistics, Epidemiology
and Informatics, German Childhood Cancer Registry, Obere Zahlbacher
Strasse 69, 55131 Mainz, Germany. Fax: 149-6131-17-2968.
E-mail: kaatsch@imbei.uni-mainz.de
Received 19 July 2007; Accepted after revision 8 November 2007
DOI 10.1002/ijc.23330
Published online 7 December 2007 in Wiley InterScience (www.interscience.
wiley.com).

722

Exact distanceof residence
from nearest npp
All cancers <5y: n 5 1592
leukaemias <5y: n 5 593<5 years
16 npp (subset
of 18 nnp)
1980–2003
Recentstudy

Case control study

Counties(up to 80 km)

In 2007 (19)Community in
5/10/15 km zones
All cancers <15y: n 5 550
leukaemias <15y: n 5 182
leukaemias <5y:n 5 107<15 years
18 npp and2 researchplants1991–1995
Study 2Ecological study

15 km vicinity basedon communities

In 1998 (17)Community in
5/10/15 km
in 1992 (15) zones
All cancers <15y: n 5 812
leukaemias <15y: n 5 279
leukaemias <5y: n 5 153<15 years
18 npp and2 researchplants1980–1990
Study 1

Ecological study

15 km vicinity basedon communities

In 1992 (15)Exposure surrogate
Date publishedCases (by disease and age)Age group
npp included
Study region
Study type
Study period
Study

TABLE I – DESIGNS OF STUDIES ON CHILDHOOD CANCER IN THE VICINITY OF NUCLEAR POWER PLANTS (NPP) PERFORMED AT THE GERMAN CHILDHOOD CANCER REGISTRY(PREVIOUS STUDIES 1 AND 2 COMPARED TO RECENT STUDY)

KAATSCH ET AL.

FIGURE 1 – Study region composed by different study areas (shaded
counties) surrounding 16 West German nuclear power plants included(indicated by name and dots) (Lingen/Emsland to be counted twice
due to a distance of 2 km between 2 different plants). [Color ﬁgure can be viewed in the online issue, which is available at www.
interscience.wiley.com.]Material and methods
We conducted a case control study where cases were children
registered with the GCCR for a malignant disease and populationbased matched controls (1:3) were selected from the records of thecorresponding registrar’s ofﬁce.
The geographical area covered by the study comprises 41 counties in the vicinity of 16 West German power plant sites. For eachsite, generally, 3 neighboring counties were identiﬁed: the county
where the power plant is located, the immediately neighboring
county and the next county in eastern direction (to account for prevailing westerly winds in Germany) (Fig. 1).
The study group includes all children diagnosed of a malignant
disease (or nonmalignant brain tumor) from January 1, 1980
through December 31, 2003, who had been diagnosed before theirﬁfth birthday, who were living in the study area when diagnosed,
and who had been registered with the GCCR. Depending on theoperation time of the plants, inclusion periods may be shorter insome areas (starting 1 year after entering operation at the earliest,
ending 5 years after cease of operation at the latest). Diagnoses
are classiﬁed according to the International Classiﬁcation ofChildhood Cancer (ICCC).20 Leukaemia cases are grouped under
ICCC category I, that is, Ia for acute lymphoid, Ib for acute nonlymphocytic leukaemia.
For all cases, controls from the records of the appropriate registrar’s ofﬁce were selected. The controls were matched for date of

723

CHILDHOOD LEUKAEMIA AND GERMAN NUCLEAR POWER PLANTS

birth (as closely as possible), age, sex and nuclear power plantarea (at the date of diagnosis). First, communities out of the respective area were selected randomly by weighting communities
according to their population (considering sex, age, year of diagnosis). Communities were then asked to provide addresses andnames of children ﬁtting the matching criteria. From these lists,
the control with date of birth closest to that of the case wasselected.
The distance of the family’s place of residence at the time of diagnosis (corresponding data in controls) from the chimney of thenearest nuclear power plant was ascertained. The addresses were
geocoded. The main question of this investigation was whether or
not the cases’ places of residence are closer in proximity to thepower plants than those of the random controls from the population. Analyses were performed for all leukaemia and speciﬁed
diagnostic subtypes (ICCC categories Ia and Ib). A conditional
logistic regression model was ﬁtted using case control status as theindependent variable. The inverse distance function was included
as the continuous variable of the model. For all leukaemia combined, the possibility of a quadratic model (second order polynomial) was investigated and assessed by the Akaike information
criterion. If this ﬁts better than the untransformed modelling, thequadratic model is applied to all subtypes. For each model, theregression coefﬁcient b was estimated and the lower one-sided
95% conﬁdence limit (lower 95%-CL) was determined.
A secondary approach, speciﬁed beforehand, was explored bydichotomising residential proximity to the nearest power plant.
The 2 categories to be compared were ‘‘residential proximity up to
5 km’’ and ‘‘residence at larger distance.’’ Odds ratios (OR) andlower 95%-CL were estimated. The same procedure was applied
for the 10-km distance. To compare the results of the categorical
data analysis with those of the continuous variable calculation, theOR for the mean of residential proximity within the 5-km zone
was derived from the estimated regression curve as well.
To ensure the correctness of our analyses, all relevant computations were repeated independently by a statistician from the coordinating centre of clinical trials of the university of Mainz.
Whereas the previous studies had determined the risk estimates
as RR with two-sided 95%-conﬁdence interval (CI), the recent
study, asking a one-sided question, uses OR with lower 95%-CL.

FIGURE 2 – Estimated dose response curvefor leukaemias (upper curve) based on conditional logistic regression model (593 cases,
1,766 matched controls; distance axis cut off
at 50 km). Lower curve: estimated lower onesided 95% conﬁdence band.21 Dotted lines:
categorical results for inner 5- and 10-km
zone. [Color ﬁgure can be viewed in the
online issue, which is available at www.
interscience.wiley.com.]

For comparison reasons, the ﬁndings of the recent study will also bereported for the time periods used in Studies 1 and 2 (1980–1990,
1991–1995 and for comparison 1996–2003), using one-sided tests.
Results
The study includes a total of 593 leukaemia cases and 1,766
matched controls. Table II shows the age and sex distribution as
speciﬁed by the matching criteria and the number of cases fordiagnostic subtypes.
The dose–response curve for the analysis of the continuous distance measure is shown in Figure 2. On the basis of this curve, theﬁtted OR at 5-km distance is 1.42 (lower 95%-CL: 1.14) and the
expected mean effect inside the inner 5-km zone would be OR 5
1.76 (lower 95%-CL: 1.24).
For all leukaemia combined, there is a statistically signiﬁcanttrend for 1/(distance in km) with a positive regression coefﬁcientof 1.75 (lower 95%-CL: 0.65) (Table III). This indicates a negative trend for distance. Cases live closer to nuclear power plants
than the randomly selected controls. The regression coefﬁcients
TABLE II – DISTRIBUTION OF LEUKAEMIA CASES (N 5 593) AND CONTROLS(N 5 1766) BY SEX, AGE (YEARS) AND DIAGNOSTIC SUBTYPES
Cases

Boys
Girls
Age 0 to 1
Age 1 to 2
Age 2 to 3
Age 3 to 4
Age 4 to 5
Age 5 to 6*
Acute lymphoidleukaemias
Acute non-lymphocytic
leukaemias
Other leukaemias*

Controls

Absolute%

Absolute

%

323
270
51
102
158
166
116
0
512

54.5
45.5
8.6
17.2
26.6
28.0
19.6
0.0
86.3

963
803
156
296
459
498
347
10
1523

54.5
45.5
8.8
16.8
26.0
28.2
19.7
0.6
86.2

75

12.6

225

12.7

6

1.0

18

1.0

Controls matched to cases aged 4–5.

724

KAATSCH ET AL.

TABLE III – ESTIMATED PARAMETERS FROM THE CONDITIONAL LOGISTIC
REGRESSION MODEL WITH CONTINUOUS EXPOSURE (1/DISTANCE IN KM)
FOR LEUKAEMIA AND SUBTYPES (UNDER 5 YEARS OF AGE)
Diagnostic group

b

Lower
95%-CL

Cases(N)

Controls(N)

All leukaemias
Acute lymphoidleukaemias
Acute non-lymphocytic
leukaemias

1.75
1.63

0.65
0.39

593
512

1.766
1.523

1.99

20.41

75

225

b, regression coefﬁcient; 95%-CL, one-sided 95% conﬁdence limit.
TABLE IV – ESTIMATED ODDS RATIOS (OR) AND HARMONIC MEAN OFDISTANCE FROM PLACE OF RESIDENCE TO NEAREST NUCLEAR POWER
PLANT (NPP) BY DISTANCE CATEGORIES FOR ALL LEUKAEMIAS (UNDER
5 YEARS OF AGE)
Harmonic mean OR derived fromOR
Cases Controls
continuous
Distance (km) of distance fromcategorical (N)(N)
residence to nearest
regressionnpp (km)model<5
5 to <10
10 to <30
30 to <50
50 to <70
70

3.09
7.62
17.79
37.45
56.98
73.59

1.76
1.26
1.10
1.05
1.03
1.02

2.27
1.09
1.01
1.11
0.90
1.00*

37
58
332
135
27
4

54
173
1048
387
92
12

*

Reference category.

for acute lymphoid leukaemia and acute non-lymphocytic leukaemia are 1.63 (lower 95%-CL: 0.39) and 1.99 (lower 95%-CL:
20.41); the latter value is not statistically signiﬁcant because of
the comparatively lower number of cases (Table III). For all leukaemias, the linear-quadratic model did not ﬁt sufﬁciently better
than the pure linear model.
When leaving each nuclear power plant out of the calculations
one by one, the results change only marginally: the regression coefﬁcients vary between 1.39 and 2.09, all results remain statistically signiﬁcant. The maximum deviation from the overall coefﬁcient of
1.75 is seen when analysing the data excluding the nuclear power
plant of Kr€ummel (regression coefﬁcient: 1.39 with lower 95%-CL
of 0.14). In the surrounding area of Kr€ummel, a well-known increaseof childhood leukaemia incidence was observed since 1990.16
Table IV shows the OR based on an analysis of distance categories and the OR derived from the continuous ﬁtted curve describedin Table III. The categorical model shows a relatively high OR in
the inner 5-km zone, while they are near 1.00 outside this zone.
The rather steeply decreasing ﬁtted regression curve (Fig. 2)
describes this observation rather well, while somewhat overestimating the effect in the 5–10-km zone.
Comparing subjects living within 5 or 10 km from the nuclear
power plant with those outside the respective zone in the categorical (dichotomous) analysis, a statistically signiﬁcant OR of 2.19
(lower 95%-CL: 1.51) is seen for residential proximity within
5 km compared to residence outside this area (Table V). For the
10-km zone, an OR of 1.33 (lower 95%-CL: 1.06) was observed.
Regarding acute lymphoid leukaemia, the categorical analysis
shows an OR of 1.98 for the 5-km zone and an OR of 1.34 for the
10-km distance (lower 95%-CLs: 1.33 and 1.05) (Table V). For
acute non-lymphocytic leukaemia, the risk estimate of an OR of
3.88 (lower 95%-CL: 1.47) for the 5-km zone is almost double therisk estimate determined for acute lymphoid leukaemia and theestimate is 1.30 for the 10-km distance. However, due to the comparatively low number (10 cases) the latter is not statistically signiﬁcant (lower 95%-CL: 0.66).
Table VI lists the results of the categorical analysis for 5 km
and the comparable ﬁndings from the previous studies of the
GCCR (Studies 1 and 2). For the total study period covered by theprevious 2 studies (1980–1995), an RR of 1.49 (95%-CI: 0.98–
2.20) was found. Regarding the total study period of the recent

TABLE V – ESTIMATED ODDS RATIOS (OR) FOR TWO DISTANCE
CATEGORIES FOR ALL LEUKAEMIAS AND SUBTYPES(UNDER 5 YEARS OF AGE)
OR

Lower
95%-CL

Cases in the
5-km zone (N)All leukaemias
5 km to >5-km zone
10 km to >10-km zone

2.19
1.33

1.51
1.06

37
95

Acute lymphoid leukaemias
5 km to >5-km zone
10 km to >10-km zone

1.98
1.34

1.33
1.05

30
84

Acute nonlymphocytic leukaemias
5 km to >5-km zone
3.88
10 km to >10-km zone
1.30

1.47
0.66

7
10

95%-CL, one-sided 95% conﬁdence limit.
TABLE VI – RESULTS OF STUDIES ON CHILDHOOD LEUKAEMIA (UNDER
5 YEARS OF AGE) IN THE VICINITY OF NUCLEAR POWER PLANTS PERFORMED AT THE GERMAN CHILDHOOD CANCER REGISTRY (PREVIOUS
STUDIES 1 AND 2 COMPARED TO RECENT STUDY)
Study periods

Previous studies
1980–90 Study 1
1991–95 Study 2
1980–95 Study 1 1 2
Recent study
1980–1990 (periodof study 1)
1991–1995 (periodof study 2)
1980–1995 (period ofprevious studies 1 1 2)
1996–2003 (period
following previous
studies)
1980–2003 (total
recent study period)

RR/OR

Conﬁdence
intervals/Lower
conﬁdence limits

Cases
5-km zone

3.011
1.391
1.491

1.25; 10.311
0.69; 2.571
0.98; 2.201

N 5 19N 5 12N 5 31

3.002

1.542

N 5 13

2.102

1.042

N 5 10

2.53

2

2

1.57

N 5 23

1.78

2

2

0.99

N 5 14

2.192

1.512

N 5 37

Relative Risks (RR) and Odds Ratios (OR) by different study periodsin the inner 5 kilometre zone (periods shown analogous to periods of previous studies).
1
Relative risk resulting from ecological study, two-sided 95%-conﬁdence interval. –2Odds ratio resulting from case control study, onesided lower 95% conﬁdence limit.

study (1980–2003), the OR is 2.19 (lower 95%-CL: 1.51). Consistency of results is predominantly seen in the ﬁrst study period(1980–1990) for which the exploratory analysis of Study 1
prompted the next 2 studies: the 2 risk estimates for the ﬁrst study
period are nearly identical (3.01 for the previous study, 95%-CI:
1.25–10.31; 3.00 for the recent study, lower 95%-CL: 1.54). As tothe time period following the previous 2 studies (1996–2003) therisk estimate of 1.78 (lower 95%-CL: 0.99) determined in the
recent study is lower than that for the previous time periods.

Discussion
Our study showed a positive relationship between the diagnosisof childhood leukaemia and the residential proximity to the nearest nuclear power plant. This result is largely attributed to cases inprevious studies as there is clearly some overlap between thosestudies, especially regarding the ﬁndings in the inner zone aroundnuclear plants.
The strength of the recent study is the availability of the individual measurement of residential proximity to the nearest nuclear
power plant for each subject, as opposed to the previous ecologicalstudies based on aggregate data. The distance measurements havebeen established with a precision of about 25 m. Whereas the pre-

CHILDHOOD LEUKAEMIA AND GERMAN NUCLEAR POWER PLANTS

vious studies were based on a comparison of incidence rates only,
we now have a case control approach.
An inverse relation to distance was used to describe the relation
between proximity to the nearest nuclear power plant and the occurrence of leukaemia. A linear quadratic model did not ﬁt better to ourdata. Most likely, potential exposure to radioactive emission of nuclear power plants would also be inﬂuenced by other factors such as
topography or weather conditions (wind, precipitation).
Precise data on exposure would be desirable, for example, frommeasurement of radiation exposure in the subjects, however, suchdata are not available. It was therefore decided to work with the distance measure, that is, proximity to the nearest nuclear power plant.
It was not possible to account for the fact that children will naturally
spend time at places other than their home address. Moreover, theresidential history of the study subjects was not available. However,as cases and controls may be moved before diagnosis of cancer (orbefore corresponding date for controls) this nondifferential misclassiﬁcation would lead to an underestimation of the risk. Other potential individually sources of exposure to ionising radiation could not
be obtained for the whole study group.
Overall, the willingness to supply addresses of potential control
subjects was slightly lower among communities near power plants
than in areas further away (control recruitment in the 5-km innerzone: 84%, outside the 5-km zone: 90%). A more restrictive generalbehavior of local authorities in the close neighborhood to nuclear
power plants could be explained because of general concern in theseregions. A sensitivity analysis excluding cases and controls fromthose communities who did not supply any or not all controls led toa negligible change in the parameter estimate (1.73 as opposed to1.75). For 8.6% among a total of 2,359 study families, the distancecould only be estimated using midpoint of the street or centre of thetown. Most likely this has no relevant impact on the results.
The association observed may possibly be inﬂuenced by confounders (like social class, pesticides, factors inﬂuencing immunological factors, exposure to other ionizing radiation). To assess
this, a subset of the study subjects (diagnosed 1993 or later) wasinterviewed. Because response rates vary remarkably with the distance to the plants (total response: 78% for cases, 61% for controls; response in the inner 5-km zone: 63% for cases, 45% forcontrols), no conclusions on the relationship between potential
confounders and the reported ﬁndings can be drawn.
On the basis of the categorical analysis, our result indicates that
20 out of the total observed 37 leukaemia cases living within
the 5-km zone are attributed to the fact that they are living in this
5-km zone. These are 0.8 cases/year in the under 5-year-olds or
0.3% of the roughly 6,000 German children diagnosed with leukaemia in this age group (1980–2003).
There is an abundance of publications on the issue of childhood
leukaemia near nuclear plants which cannot be referenced systematically at this place (see Ref. 22 for a review). Whereas some cancer
clusters in children have been found near nuclear power plants(Kr€ummel, Sellaﬁeld/Windscale, Dounreay),16,23,24 it is also seen,
when considering all relevant studies, that the assumption of a generally increased disease rate around nuclear power plants is notupheld.22 A recent study has conﬁrmed this observation for France.25
Generally, the radiation exposure near a nuclear power plant inroutine operation is extremely small compared to exposure to ionising radiation of the general public from other sources (e.g., cosmic, terrestrial or medical irradiation). While annual natural radiation exposure in Germany is about 1.4 milli Sievert and the annual
average exposure from medical examinations is about 1.8 milli

725

26

Sievert per year, radiation exposure near German nuclear power
plants is a factor of 1,000–100,000 less.12 The reported ﬁndings
were thus not to be expected under radiation biological and epidemiological considerations.
It should be noted that data of the previous GCCR studies andthe recent study are not independent of each other. The increased
risk estimates were thus not unexpected. The overlap of cases inthe studies is given, because (i) those 16 nuclear power plants
included in the recent study were also part of the previous studies
and (ii) cases diagnosed between 1980 and 1995 entered both theprevious studies and the recent study. The overlap especially isgiven for those cases reported from the inner zone while there ispractically no overlap regarding cases outside the 15-km zone.
The magnitude of overlap is veriﬁed by the following ﬁgures:
regarding leukaemia cases lived in the inner 5-km zone, 25 out of
those 37 cases of the recent study had already been included in theprevious studies; only 12 cases from the recent study were thus
not previously included; on the other hand, 6 cases from the previous studies are not included in the recent one.
The 11-year time period of the ﬁrst of the previous studies(1980–1990) had shown a statistically signiﬁcant result in exploratory subgroup analyses. This led to the following 2 studies andhad a deﬁnite impact on the design of the recent study covering a
total of 24 years (1980–2003). The ﬁrst of the previous studies
reported an RR of 3.01 for leukaemias within the 5-km zone andthe recent study for the same period and group of patients an ORof 3.00 (1980–1990). Still, the results of the recent study for the
1996–2003 period, which had not been included in the 2 previous
studies, also show a trend towards a risk increase.
To achieve more convincing results as from the previous ecological studies a design was chosen, in which for each subject individually the residential proximity to the nearest nuclear power plant wasdetermined. So misclassiﬁcation was reduced compared to the previous German studies, in which exposition was determined only
roughly in categories of about less than 5 km, 5–10 km and 10–15
km. Additionally, new data of further 8 years are included.
The recent study conﬁrmed previous German ﬁndings regarding
leukaemia in the 5-km zone of nuclear power plants. However,regarding the period not included in the previous studies, that is,basically independent data, a tendency towards an increase ofrisk with closer residential proximity is also seen. In view of thefact that this result was not to be expected under current radiationepidemiological knowledge and considering that there is no evidence of relevant accidents and that possible confounders could
not be identiﬁed, the observed positive distance trend remains
unexplained.
Acknowledgements
The authors are responsible for the content. The authors
acknowledge gratefully Robert-Koch-Institute, Berlin, for performing an audit and coordinating centre of clinical trials (Koordinierungszentrum f€
ur Klinische Studien KKS), University ofMainz, for performing an independent analysis of the data set. The
authors gratefully acknowledge the contribution by the German
Society of Paediatric Oncology and Haematology (GPOH) and theassociated Therapy Optimisation Trials who provide data on a regular basis and thus contribute to the high degree of completenessand data quality at the German Childhood Cancer Registry. The
authors are also indebted to Prof. J. Michaelis, Mainz, for constructive critical review of the manuscript and Dr. J. Sch€uz,
Copenhagen, who helps during grant application.

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