Epidemiological studies of leukaemia in children and young
adults around nuclear facilities: a critical review

Aims and structure of the report
An epidemiological study published in late 2007 described an increased risk of leukaemia in children
under 5 living within 5 kilometres of German nuclear power plants. A great deal of research has
been carried out on this subject since the early 1980s. The aim of this report was to provide a
synthesis and critical analysis of results related to the risk of leukaemia in children and young adults
aged under 25 living close to nuclear facilities. The report is structured in three sections:•a reminder of the main characteristics of childhood leukaemia and a description of the methods
used to conduct epidemiological studies;•

the most exhaustive review possible of epidemiological studies published in the international
literature describing the frequency of leukaemia close to nuclear facilities in different countries
around the world. A critical analysis is made of the published results. Some results from studies
not focused on nuclear facilities are also presented. The methodological limitations associatedwith descriptive studies are explained and discussed;•the last section discusses the possible causes of childhood leukaemia and the main hypotheses
explored to explain certain clusters of cases observed locally close to some nuclear sites.

Appendices at the end of the document provide additional explanations of the concepts andmethods used in epidemiology and statistics, and of the classification of malignant haemopathies.

Background information and methods
Leukaemia is not a common disease among children: each year in France there are around 470 newcases and 75 deaths from childhood leukaemia in a population of approximately 12 million children(aged 0-14 years). Acute lymphoblastic leukaemia accounts for nearly 80% of cases of leukaemia inchildren. There is a peak in the frequency of this type of leukaemia between 1 and 6 years. There
are few recognised risk factors of childhood leukaemia: trisomy 21 or Fanconi anaemia, external
exposure to ionising radiation at high doses or taking alkylating drugs used in chemotherapy. Otherfactors are suspected but their role has not been confirmed so far: exposure to low doses of ionisingradiation, electromagnetic fields, pesticides, benzene, infectious agents, etc. Although many
possible risk factors have been suggested, there is little information available at present to explain
the causes of leukaemia and 90% of cases remain without known cause.

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The method used for this synthesis is based on bibliographical research on the Scopus and PubMed
databases. Additional documents have been obtained from IRSN’s archives and direct contact withresearchers in France and abroad. In total, several hundred documents (reports, articles in scientificjournals) on the risk of leukaemia in young people aged under 25 around nuclear sites have beenpublished. The work done has varied in nature and quality: local or multi-site cluster studies, casecontrol or cohort studies, radio-ecological studies, dosimetry research, etc. The review distinguishes
between two types of research:•

descriptive studies, the aim of which is to estimate the frequency of leukaemia, andpossibly to detect excess risk within a population;•analytical research, the aim of which is to find the factors that could explain excess risk ofleukaemia within a population.

Review of descriptive studies
Descriptive studies are trying to answer the question “Is the frequency of leukaemia close to aparticular site higher than elsewhere?”. It is important to point out that these studies cannot findthe factors likely to explain clusters of cases.
In total, descriptive results are available for 198 nuclear sites in ten different countries: the United
Kingdom, Germany, France, Sweden, Spain, the United States, Canada, Japan, Switzerland andIsrael. A review was conducted of all these results, distinguishing between local studies of a specificsite and multi-site studies looking simultaneously at a group of sites in a country, and therefore
covering a larger population. Evaluation criteria were applied in order to assess the results
collected. The criteria relate to the type of data considered (morbidity/mortality), the geographicalarea studied (relevance of the size and boundaries of the areas considered), the power of the study(ability to reveal a low excess risk), the reproducibility of the results (excess revealed by different
methods), the statistical significance of the excess, the validity of the statistical methodology, andfinally the persistence of the excess over time.
At the 198 sites surveyed, three excesses met the stated evaluation criteria and can be considered
confirmed clusters. These are the clusters at Seascale (near the Sellafield plant in England), Thurso(near the Dounreay plant in Scotland) and Elbmarsch (near the Kruemmel power plant in Germany).
Other clusters are well documented, particularly in the United Kingdom close to the Aldermaston
and Burghfield sites and in France close to the La Hague reprocessing plant, but the information
currently available is not conclusive about the existence of confirmed excesses.
Among the multi-site studies surveyed (25 studies in 8 different countries), those that best meet theevaluation criteria are the recent studies carried out in the United Kingdom, Germany and France.
At the level of all the sites, these studies do not show an increased risk of leukaemia in children andyoung adults close to the nuclear sites. The observation of an excess of leukaemia in children aged
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0-4 years around German nuclear power plants is not backed up by studies carried out in othercountries. Nevertheless, it should be pointed out that few studies have provided specific results forthis age range.
Other studies show that localised excesses in cases of childhood leukaemia have also been detected
where there is no nuclear site. Furthermore, several studies show spatial and temporal clusters of
the incidence of leukaemia in children that are independent of the presence of potential sources ofrisk.
The discussion underlines the limitations of descriptive studies, which make interpreting the resultsdifficult. Studies of the risks of leukaemia around nuclear sites are many and varied, so it isnecessary to look at each new result in the light of the available scientific knowledge.

Review of research into the causes of observed localised excesses
Following descriptive studies in which leukaemia clusters have been observed close to certain
nuclear facilities, much research has been launched to identify factors that explain these excesses,
in particular close to the sites at Sellafield and Dounreay, and Aldermaston and Burghfield in theUnited Kingdom, La Hague in France and Kruemmel in Germany. The nature of and protocols used
for this research have varied: epidemiological studies (geographical case, case-control or cohort
studies), measurements of doses received by the population or radio-ecological assessments. Three
principal hypotheses have been put forward to try to explain a higher risk being observed close tocertain nuclear facilities.
•the hypothesis of a link with environmental exposure due to radioactive or chemical
discharges from the nuclear facilities;•the hypothesis of a link with the exposure of fathers to ionising radiation before theconception of children;•the hypothesis of the leukaemia being caused by an infection linked to population mixing
associated with major construction work.

Research into a possible link with environmental exposure indicates that the doses due to discharges
from the nuclear facilities are low.
The hypothesis of a link with the workplace exposure of fathers to external ionising radiation before
conception now seems to have been ruled out.
The hypothesis of infection linked to population mixing around nuclear sites is backed up by several
epidemiological results. According to some authors, this hypothesis could partly explain theexcesses observed close to certain sites (in particular Sellafield and Dounreay). However, it has not
so far been possible to identify or isolate the infectious agent(s) involved.

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The implication of other environmental factors has been considered by some publications, such as
electromagnetic fields due to high-voltage power lines, pesticide use in gardens or fields, thepresence of other industrial sites or high exposure to radioactivity of natural origin. Nevertheless,these factors are not specific to the sites where the nuclear facilities are located and so far none ofthem is a recognised risk factor of childhood leukaemia.
At present, although several suggestions have been put forward, the origin of the clusters observed
close to certain nuclear sites has not been established. However, it should be noted that most ofthese studies have methodological limitations (geographical case studies or studies of smallpopulations), making it difficult to detect any causal link. In addition to this difficulty there is alack of knowledge or the risk factors associated with childhood leukaemia. Carrying out large-scale
analytical studies such as those under way in France, based on the national register of malignant
haemopathies in children, could provide a better understanding of the causes of clusters ofchildhood leukaemia.
Conclusion
Since the 1980s, many descriptive studies have estimated the frequency of leukaemia in young
people close to nuclear facilities. These studies meet a demand for information on the part of local
populations and constitute a necessary addition to the discussion on the effects of low
environmental doses. The bibliographical review shows wide diversity in the approaches taken andmethods used.
Localised excesses of cases of childhood leukaemia exist in the United Kingdom close to thereprocessing plants at Sellafield and Dounreay, and in Germany close to the Kruemmel nuclear
power plant. Nevertheless, none of the multi-site studies currently available shows an increase in
the frequency of leukaemia overall in children and young people aged 0-14 or 0-24 close to nuclear
sites.
A recent epidemiological study described an excess of leukaemia in children aged 0-4 around
German nuclear facilities. To date, no similar excesses have been observed in studies in othercountries. The published German study offers no suggestions to explain the excess observed.
Furthermore, much research has looked for explanations for excesses of leukaemia observed aroundcertain nuclear sites in multiple potential risk factors. Among the different areas explored, thehypothesis of infection linked to population mixing around the nuclear sites seems to be the most
supported. However, the infectious agent(s) involved have not so far been found.
Determining the causes of excesses of leukaemia observed locally close to certain nuclear sites islimited by a lack of knowledge of the risk factors of childhood leukaemia. This means that its
necessary to develop analytical studies on a larger scale, at national or international level.

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