"CLUSTER" ANALYSIS has become a widely used term for the study of spatial disease patterns in small geographical areas. Although ecological by definition, many small area studies have been supplemented with investigations at the individual level. Cluster analysis then extends beyond the ecological perspective, and Rose has referred to it as "microepidemiology." Although some researchers have criticized microepidemiology for its conceptual and methodological limitations,[3,4] some well-known examples nevertheless prove its principal potential as a useful tool in environmental epidemiology.[5-9]
Results of cluster analysis and microepidemiology have become key arguments in a debate on leukemia risks for children who live in the vicinity of nuclear facilities. Researchers have reported increased risks in geographical studies in England and Wales, Scotland, the United States,[10-14] Canada, Germany,[16-21] and more recently in France.[22,23]
The rural community of Elbmarsch includes several small villages located at the southern bank of the Elbe River, 35 km southeast of Hamburg in northern Germany. Between February 1990 and May 1991, professionals diagnosed five cases of leukemia in children under age 15 y in the rural community of Elbmarsch. We excluded another leukemia case (i.e., 21-y-old male) from the analysis. In early summer 1995, professionals diagnosed another 10-y-old child with acute leukemia in one of the villages, thus increasing the total number of childhood leukemia cases to six (Table 1). Fortunately, leukemia occurs rarely in childhood. In Germany, the age-adjusted incidence for all types of leukemia combined in children below age 15 y is 4.3/100 000 person-years (data for 1989-1993). The leukemias account for approximately 30% of all malignancies that occur before age 15y.
Table 1. -- Childhood and Juvenile Leukemia Cases in the Rural Community Elbmarsch, Northern Germany
2. With respect to a given dose of radiation, the relative risk for leukemia increases with younger age by a factor of 4-5 (adults versus children below the age of 5 y). For prenatal exposure, we can derive a factor of approximately 70 from data of the Oxford Survey of Childhood Cancers (OSCC).[67,73]
3. Preconceptional exposure[36-42] may add a potential exposure pathway that cannot yet be accounted for in risk coefficients. Incorporated radionuclides may be of particular concern, but the magnitude of this potential effect is unknown presently.
4. Effects of complex combinations of environmental exposures are still very poorly understood. Nevertheless, synergistic effects between irradiation and chemical exposures could well enhance the leukemogenic potential of either factor.[74,75]
Most important, exposure assessment in such studies is usually inadequate. Routine environmental radiation surveillance can fail to detect chronic exposures from short-lived [Beta]-emitters or from extremely inhomogeneous spatial/temporal distributions of radionuclides. Indeed, we speculated earlier that elevated rates of structural chromosomal aberrations in a casual sample of five parents of leukemia cases and four other adult Elbmarsch residents would be compatible with past releases of short-lived fission products, which might have been missed by routine surveillance (2.4 dicentric chromosomes/1 000 metaphases observed, 0.4/1 000 expected; p [is less than] .0001).
The recent results of high-geographical-resolution incidence mapping also revealed a significantly elevated leukemia incidence for adults in the 5-km-radius region around the plant during the years 1984-1993 (all leukemias: 41 cases observed, 30 expected; SIR = 128; p [is less than] .05).
At this time, microepidemiology cannot provide any further insight. Individual exposure to releases from the plant as well as to known or other suspected other risk factors for childhood and adult leukemia need to be investigated quantitatively. Exposure assessment will be crucial in a large case-control study that has been commissioned recently by the Ministry for the Environment, Natural Protection and Forests of Schleswig-Holstine and the Ministry of Social Affairs of Lower Saxony.
Since submission of this manuscript, three additional childhood leukemia cases (all males) were ascertained in the 0-5-km region around the nuclear power plant Kruemmel. Two of the cases were diagnosed with acute lymphatic leukemia in 1995 and 1996, respectively. The third child had been diagnosed with acute myeloid leukemia already in 1994, but became known to us only very recently. These additional cases bring the total childhood leukemia cases in the immediate vicinity of the plant to nine. The appearance of new cases strongly indicates that childhood leukemia incidence remains elevated in the 0-5-km region around the plant. We cannot presently exclude the possibility that any underlying causal process might be ongoing.
Submitted for publication March 22, 1996; revised; accepted for publication August 26, 1996.
Requests for reprints should be sent to Wolfgang Hoffmann, Bremen Institute for Prevention Research and Social Medicine, Grunen-str. 120, D-28211 Bremen, Germany.
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