Childhood Leukemia Cluster Research Articles

The Elbmarsch Leukemia Cluster: Are There Conceptual Limitations in Controlling Immission from Nuclear Establishments in Germany?

The childhood leukemia cluster in the proximity of the German nuclear establishments of Geesthacht is unique in its spatial and temporal concentration. After a steep increase in cases in 1990, the cluster continues to show a significant increase up to the present. Early investigations of blood samples from a casual sample of local residents showed an increase in dicentric chromosomes in lymphocytes, indicating exposure exceeding dose limits. Analyses of the immission data revealed several unexpected deliveries of fission and activation products in the environment but provided no explanation of the source. Because of the observed overdispersion of dicentric chromosomes in cells, the idea of a contribution by densely ionizing emitters was compelling. The routine programs, however, do not include alpha emitters. These were measured in specific studies that proved contamination by transuranic nuclides. As shown in the present investigation, routine environmental surveillance programs support the occurrence of an accidental event near Geesthacht in September 1986. Until now, neither the cause nor the complete scenario of the activity release could be established. The ongoing discussion highlights limitations in the immission-control concept, which is predominantly based on gamma-radiation monitoring.

Overlooked in Fallon?

Overlooked in Fallon?

Factors controlling tungsten concentrations in ground water, Carson Desert, Nevada

An investigation of a childhood leukemia cluster by US Centers for Disease Control and Prevention revealed that residents of the Carson Desert, Nevada, are exposed to high levels of W and this prompted an investigation of W in aquifers used as drinking water sources. Tungsten concentrations in 100 ground water samples from all aquifers used as drinking water sources in the area ranged from 0.27 to 742 μg/l. Ground water in which W concentrations exceed 50 μg/l principally occurs SE of Fallon in a geothermal area. The principal sources of W in ground water are natural and include erosion of W-bearing mineral deposits in the Carson River watershed upstream of Fallon, and, possibly, upwelling geothermal waters. Ground water in the Fallon area is strongly reducing and reductive dissolution of Fe and Mn oxyhydroxides may be releasing W; however, direct evidence that the metal oxides contain W is not available. Although W and Cl concentrations in the Carson River, a lake, and water from many wells, appear to be controlled by evaporative concentration, evaporation alone cannot explain the elevated W concentrations found in water from some of the wells. Concentrations of W exceeding 50 μg/l are exclusively associated with Na – HCO 3 and Na–Cl water types and pH > 8.0; in these waters, geochemical modeling indicates that W exhibits <10% adsorption. Tungsten concentrations are strongly and positively correlated with As, B, F, and P, indicating either common sources or common processes controlling their concentrations. Geochemical modeling indicates W concentrations are consistent with pH-controlled adsorption of W. The geochemical model PHREEQC was used to calculate IAP values, which were compared with published Ksp values for primary W minerals. FeWO 4, MnWO 4, Na 2WO 4, and MgWO 4 were undersaturated and CaWO 4 and SrWO 4 were approaching saturation. These conclusions are tentative because of uncertainty in the thermodynamic data. The similar behavior of As and W observed in this study suggests ground water in areas where elevated As concentrations are present also may contain elevated W concentrations, particularly if there is a mineral or geothermal source of W and reducing conditions develop in the aquifer.

Temporal changes in water quality at a childhood leukemia cluster.

Since 1997, 15 cases of acute lymphocytic leukemia and one case of acute myelocytic leukemia have been diagnosed in children and teenagers who live, or have lived, in an area centered on the town of Fallon, Nevada. The expected rate for the population is about one case every five years. In 2001, 99 domestic and municipal wells and one industrial well were sampled in the Fallon area. Twenty-nine of these wells had been sampled previously in 1989. Statistical comparison of concentrations of major ions and trace elements in those 29 wells between 1989 and 2001 using the nonparametric Wilcoxon signed-rank test indicate water quality did not substantially change over that period; however, short-term changes may have occurred that were not detected. Volatile organic compounds were seldom detected in ground water samples and those that are regulated were consistently found at concentrations less than the maximum contaminant level (MCL). The MCL for gross-alpha radioactivity and arsenic, radon, and uranium concentrations were commonly exceeded, and sometimes were greatly exceeded. Statistical comparisons using the nonparametric Wilcoxon rank-sum test indicate gross-alpha and -beta radioactivity, arsenic, uranium, and radon concentrations in wells used by families having a child with leukemia did not statistically differ from the remainder of the domestic wells sampled during this investigation. Isotopic measurements indicate the uranium was natural and not the result of a 1963 underground nuclear bomb test near Fallon. In arid and semiarid areas where trace-element concentrations can greatly exceed the MCL, household reverse-osmosis units may not reduce their concentrations to safe levels. In parts of the world where radon concentrations are high, water consumed first thing in the morning may be appreciably more radioactive than water consumed a few minutes later after the pressure tank has been emptied because secular equilibrium between radon and its immediate daughter progeny is attained in pressure tanks overnight.

Probability estimates for the unique childhood leukemia cluster in Fallon, Nevada, and risks near other U.S. Military aviation facilities.

A unique cluster of childhood leukemia has recently occurred around the city of Fallon in Churchill County, Nevada. From 1999 to 2001, 11 cases were diagnosed in this county of 23,982 people. Exposures related to a nearby naval air station such as jet fuel or an infectious agent carried by naval aviators have been hypothesized as potential causes. The possibility that the cluster could be attributed to chance was also considered. We used data from the Surveillance, Epidemiology, and End Results Program (SEER) to examine the likelihood that chance could explain this cluster. We also used SEER and California Cancer Registry data to evaluate rates of childhood leukemia in other U.S. counties with military aviation facilities. The age-standardized rate ratio (RR) in Churchill County was 12.0 [95% confidence interval (CI), 6.0-21.4; p = 4.3 times symbol 10(-9)]. A cluster of this magnitude would be expected to occur in the United States by chance about once every 22,000 years. The age-standardized RR for the five cases diagnosed after the cluster was first reported was 11.2 (95% CI, 3.6-26.3). In contrast, the incidence rate was not increased in all other U.S. counties with military aviation bases (RR = 1.04; 95% CI, 0.97-1.12) or in the subset of rural counties with military aviation bases (RR = 0.72; 95% CI, 0.48-1.08). These findings suggest that the Churchill County cluster was unlikely due to chance, but no general increase in childhood leukemia was found in other U.S. counties with military aviation bases.

Qualitative methods in environmental health research.

Public health researchers increasingly turn to qualitative methods either on their own or in combination with quantitative methods. Qualitative methods are especially important to community environmental health research, as they provide a way to produce community narratives that give voice to individuals and characterize the community in a full and complex fashion. This article first traces the legacy of qualitative research in environmental health, then uses a case study of the author's experiences studying the Woburn, Massachusetts, childhood leukemia cluster to provide personal and scholarly insights on qualitative approaches. That material then informs a discussion of important components of qualitative methods in environmental health research, including flexible study design, access, trust, empathy, and personal shifts in the researcher's worldview, bias, and the nature of the researcher's roles. A concluding discussion addresses issues in funding policy and research practices.

A case–control study of childhood leukemia in Woburn, Massachusetts: the relationship between leukemia incidence and exposure to public drinking water

A 1981 Massachusetts Department of Public Health study confirmed a childhood leukemia cluster in Woburn, Massachusetts. Our follow-up investigation attempts to identify factors potentially responsible for the cluster. Woburn has a 130-year industrial history that resulted in significant local deposition of tannery and chemical manufacturing waste. In 1979, two of the city's eight municipal drinking water wells were closed when tests identified contamination with solvents including trichloroethylene. By 1986, 21 childhood leukemia cases had been observed (5.52 expected during the seventeen year period) and the case–control investigation discussed herein was begun. Nineteen cases and 37 matched controls comprised the study population. A water distribution model provided contaminated public water exposure estimates for subject residences. Results identified a non-significant association between potential for exposure to contaminated water during maternal pregnancy and leukemia diagnosis, (odds ratio=8.33, 95% CI 0.73–94.67). However, a significant dose–response relationship ( P<0.05) was identified for this exposure period. In contrast, the child's potential for exposure from birth to diagnosis showed no association with leukemia risk. Wide confidence intervals suggest cautious interpretation of association magnitudes. Since 1986, expected incidence has been observed in Woburn including 8 consecutive years with no new childhood leukemia diagnoses.

Estimation of x ray overexposure in a childhood leukaemia cluster by means of chromosome aberration analysis.

Only multiple X ray diagnostics could be identified as a common risk factor in a leukaemia cluster that appeared between 1985-1989 in the municipality of Sittensen in northern Germany. In order to judge if the effect could be explained by irradiation dose, estimates were done in two of the leukaemia cases and seven former patients of a practice where some of the leukaemia cases had been treated for orthopaedic reasons. The methods used for the reconstruction of doses were physical simulation and biological dosimetry by dicentric chromosomes in peripheral lymphocytes. Compared to the Bremen laboratory control the mean frequency of dicentric chromosomes in the lymphocytes of the seven volunteers was significantly elevated. An overexposure of about 12-fold could be derived compared to state of the art X raying. At least two cases of the leukaemia cluster in Sittensen can therefore be correlated to an overexposure by diagnostic X rays.

Childhood Leukaemia Clustering – Fact or Artefact?

There is a general belief that the clustering of childhood leukaemia is a widespread phenomenon and that it provides evidence for appreciable environmental influence on the incidence of the disease. We discuss this issue critically, identifying different kinds of clustering and their possible aetiological mechanisms and examining some analyses of British data. We argue that, in some cases, analyses have been used which lead to dubious conclusions, and that, allowing for multiple testing and anecdotal reporting, the total evidence for clustering is at best weak.

The probability of a cancer cluster due to chance alone

We propose to use a very simple model to test whether a cancer cluster is due to chance alone. We focus on the acute childhood leukaemia cluster in Columbus, Ohio. In 1975, 12 leukaemia cases were observed in Columbus while the expected number is 6 cases per year. According to our simple model, the probability of such an occurrence, due to chance alone, is less than 1 per cent. However, if we divide the child population of the U.S.A. into 200 regions (each region having 200 000 children) then the probability that at least one region will see, in a given year, 12 or more cases is higher than 80 per cent. So in this sense the Columbus cluster could be attributed to chance alone. However, the probability that any of the 200 regions see 18 cases or more in a given year is almost 0. Thus, a cluster of 18 or more cases in a region of 200 000 children should be regarded as highly suspicious and should be investigated. Copyright © 2000 John Wiley & Sons, Ltd.

Space-time clustering of childhood lymphatic leukaemias and non-Hodgkin's lymphomas in Sweden.

The discussion concerning clusters of childhood leukaemia has mainly been focused on their relation to the time and place of diagnosis. Recently some studies have indicated clustering not only at diagnosis, but also around time and place of birth. Space-time clustering at time of birth could be of special interest if the aetiological agent is of infectious origin and the induction of leukaemia either occurs pre- or perinatally or an infection at that time favours a poor subsequent immune response to the agent. To identify possible space-time clustering we have used the close-pair method of Knox. One-thousand-twenty recorded cases (0-14 years) of childhood acute lymphatic leukaemia and 293 cases (0-14 years) of malignant non-Hodgkin's lymphoma from Sweden between 1973-1996 were analysed. The records include date of birth and of diagnosis as well as addresses at birth and at diagnosis. A significant excess of case-pairs (25 observed, 14.9 expected, p = 0.01) was observed close in date and place of birth in the 4-14 year age group with acute lymphatic leukaemia (ALL). However there was no statistically significant clustering found around time of diagnosis. When the cases of leukaemia and the non-Hodgkin's lymphomas were combined no statistically significant clustering was obtained neither at birth nor at diagnosis. This study strengthens the evidence of space-time clustering around the birth date in children whom later developed ALL. This observation is in support of the hypothesis that pre- or perinatal infections can induce a process leading to ALL.

Clusters and clustering of childhood cancer: a review.

Methodological considerations in the study of clusters and clustering of childhood cancer are reviewed briefly. A selection of 11 studies of individual clusters of childhood leukaemia which are either particularly notable or recent and have been reported in peer review journals is then considered. Focus is placed on sources of alerts, descriptive studies, field-work studies, conclusions and communication management. Some of these studies are probably essential but they are unlikely to yield firm conclusions; studies of large data sets are recommended. No causal factor has been identified which can explain a single cluster of childhood leukaemia.

Ionising radiation and leukaemia potential risks: review based on the workshop held during the 10th Symposium on Molecular Biology of Hematopoiesis and Treatment of Leukemia and Lymphomas at Hamburg, Germany on 5 July 1997.

Unexplained clusters of childhood leukaemia have generated concern that they may be causally related to environmental exposure to ionising radiation. The workshop provides in-depth examination of the aetiology of childhood leukaemia, patterns of clustering exhibited by cases and the influence of exposure to ionising radiation. Special attention has been focussed on the EUROCLUS study of clustering of childhood leukaemia and monitoring of populations exposed to contamination following the Chernobyl accident. There is insufficient evidence to conclude that environmental ionising radiation exposure is a causative agent for small clusters such as that reported in the vicinity of the Krümmel nuclear facility

Spatial clustering of childhood leukaemia: summary results from the EUROCLUS project

The interpretation of reports of clusters of childhood leukaemia is difficult, first because little is known about the causes of the disease, and second because there is insufficient information on whether cases show a generalized tendency to cluster geographically. The EUROCLUS project is a European collaborative study whose primary objective is to determine whether the residence locations of cases at diagnosis show a general tendency towards spatial clustering. The second objective is to interpret any patterns observed and, in particular, to see if clustering can be explained in terms of either infectious agents or environmental hazards as aetiological agents. The spatial distribution of 13351 cases of childhood leukaemia diagnosed in 17 countries between 1980 and 1989 has been analysed using the Potthoff-Whittinghill method. The overall results show statistically significant evidence of clustering of total childhood leukaemia within small census areas (P=0.03) but the magnitude of the clustering is small (extra-Poisson component of variance (%) = 1.7 with 90% confidence interval 0.2-3.1). The clustering is most marked in areas that have intermediate population density (150-499 persons km[-2]). It cannot be attributed to any specific age group at diagnosis or cell type and involves spatial aggregation of cases of different ages and cell types. The results indicate that intense clusters are a rare phenomenon that merit careful investigation, although aetiological insights are more likely to come from investigation of large numbers of cases. We present a method for detecting clustering that is simple and readily available to cancer registries and similar groups.

A cluster of childhood leukemia near a nuclear reactor in northern Germany.

Between February 1990 and December 1995, professionals diagnosed six cases of childhood leukemia among residents of the small rural community of Elbmarsch in northern Germany. Five of these cases were diagnosed in only a 16-mo period between February 1990 and May 1991. All cases lived in close proximity (i.e., 500-4,500 m) to Germany's largest capacity nuclear boiling-water reactor. We calculated standardized incidence ratios and exact 95% confidence intervals for a 5-km-radius circular area around the plant. The standardized incidence ratio for the time period 1990-1995 was 460 (95% confidence interval: 210, 1,030). The analysis was restricted further to the years 1990 and 1991, and the standardized incidence ratio increased to 1,180 (95% confidence interval: 490, 2,830). Presently, this cluster of childhood leukemia cases cannot be explained in terms of established and putative risk factors--including radiation from medical sources--for childhood leukemia.

Childhood leukaemia and exposure to pesticides: results of a case-control study in northern Germany.

The association between childhood leukaemia and exposure to pesticides was examined in a population-based case-control study conducted in Lower Saxony, Northern Germany. Between July 1988 and June 1992, 219 newly diagnosed cases were identified, of whom 173 participated in the study. Two sex- and age-matched control groups were recruited: local controls from the same communities as the newly diagnosed cases of leukaemia and state controls from other randomly selected communities in Lower Saxony. An additional study group consisted of 175 cases of solid tumours. When the leukaemia cases were compared with the local controls, positive associations with parental occupational exposure, particularly agriculture-related exposure, were observed, which were statistically non-significant. A significant association was found for pesticide use in gardens (odds ratio = 2.52, 95% confidence interval: 1.0-6.1). No positive associations were seen when the leukaemia cases were compared to the state controls, but this finding could be explained by a higher proportion of state controls living in rural areas. In communities with a significantly elevated standardised incidence ratio of childhood leukaemia over the last decade (1984-1993), the prevalence of pesticide use in the garden was 21%, compared with the 10% in other communities. None of the examined risk factors were more common among cases of solid tumours. Our findings add some evidence to the hypothesis that pesticides are a risk factor for childhood leukaemia, and there are good reasons to consider abundant pesticide use in rural areas as a possible cause for clustering of childhood leukaemia.

Space-time clustering of childhood leukaemia in Greece: evidence supporting a viral aetiology

The method introduced by Knox for evaluation of space-time clustering has been applied to 872 cases of childhood (0-14 year old) leukaemia diagnosed in Greece over the 10 year period 1980-89. Greek towns are characterised by substantial population mixing due to internal migration, whereas there is relative isolation in mountainous rural areas. Predetermined space (5 km) and time (1 year) limits were used on the basis of previous reports in order to define the clustering cell. There is highly significant evidence for clustering of childhood leukaemia in Greece as a whole, the observed number of pairs that are close in both spaces and time exceeding the expected number by 5.2% (P = 0.004). The excess is particularly evident for leukaemia cases in 0 to 4-year-old children, among whom the observed number of pairs that are close in both space and time exceeded the expected number by 9.4% (P = 0.004). There is no evidence of space-time clustering for leukaemia cases older than 5 years. The overall pattern is descriptively similar in urban and semiurban areas and is especially marked for acute lymphoblastic leukaemia at the childhood peak ages (2-4 years) with an excess of 19% (P = 0.0006). In the rural population there is evidence for clustering of cases belonging to older and broader age groups, a phenomenon compatible with a delay in the development of herd immunity against putative infectious aetiological agents. The findings of the present study provide support for the hypothesis that a substantial proportion of cases of childhood leukaemia may arise as a rare sequel to exposure to an agent or agents, most probably viral in nature.

Interactive spatial data analysis in medical geography

Interactive spatial data analysis involves the use of software environments that permit the visualization, exploration and, perhaps, modelling of geographically-referenced data. Such systems are of obvious value in epidemiological research, both of an environmental and geographical nature. There is an increasing number of such software environments available on a variety of platforms and operating systems. This paper considers the use of the proprietary Geographical Information System, ARC/INFO, in a spatial analysis context, showing how the spatial analytic tools that may be added to it can be exploited by geographical epidemiologists; such tools include those for modelling possible raised incidence of disease around suspected sources of pollution. The paper also reviews the use of systems such as S-Plus and XLISP-STAT, statistical programming environments to which spatial analysis functions or libraries may be added. The use of INFO-MAP, a system designed to aid in the teaching of interactive spatial data analysis, is also highlighted. The various software environments are illustrated with reference to examples concerned with: clustering of childhood leukaemia in part of Lancashire, England; Burkitt's lymphoma in Uganda; larynx cancer in Lancashire; and childhood mortality in Auckland, New Zealand.

Epidemiological evidence of effects of small doses of ionising radiation with a note on the causation of clusters of childhood leukaemia

Effects of small doses of ionising radiation are currently estimated by extrapolation from effects observed at higher doses modified by knowledge of the results of experiments in animals or in vitro. Three are possible: reduced intelligence if the fetus is irradiated at 8-25 weeks in utero, hereditary disease, and cancer. Direct observation of the effect of small doses has been possible only for cancer. Observations on 131,000 radiation workers in the UK and the USA lead to estimates of the lifetime risks of leukaemia and all cancers close to those obtained by extrapolation, halved to adjust for the lesser effect of doses given at low dose rates, as do observations on children in Utah and the Nordic countries exposed to radioactive fallout from nuclear weapons testing, respectively, in Nevada and worldwide. Clusters of leukaemia and NHL in young people near some nuclear installations in the UK cannot be attributed to chance, local pollution with radioactive waste, or occupational exposure of their fathers before the children's conception. There remains the possibility that they result from the spread of infection in susceptible individuals from the mixing of urban and rural populations.

Viruses, clusters and clustering of childhood leukaemia: a new perspective?

Clusters of childhood leukaemia have, during a lengthy and controversial history, focussed attention on two alternative putative aetiological agents: infections and localised environmental pollution. In the United Kingdom emphasis is currently placed on the latter because of reports of localised clusters in the vicinity of two nuclear reprocessing plants. Now the most recent studies of spatial clustering in the United Kingdom also support the hypothesis that a substantial population of cases of childhood acute lymphoblastic leukaemia (ALL) arise as a rare host response to certain patterns of exposure to common infectious agents—the aberrant response model. Relevant aspects of the epidemiology of ALL are reviewed from this perspective and the hypothesis shown to be capable of unifying reported associations with different types of risk factor. It is probable that specific agent(s) are involved though none have been identified and these may share many epidemiological characteristics of herpes viruses. The possible relevance of these results to associations with prenatal parental occupational exposures to dusts and ionising radiation is explored.