Uwe Kaletsch

Risk factors for pediatric tumors of the central nervous system: Results from a German population‐based case‐control study

BACKGROUND From 1993 to 1997 we conducted two population-based case-control studies on childhood cancer and a variety of potential risk factors in Germany. One case group involved children under the age of 15 years having a tumor of the central nervous system (CNS). PROCEDURE For both studies, one conducted in the northwestern area of Germany, the other covering the whole of West Germany, incident cases were identified from the nationwide German Childhood Cancer Registry, and controls were randomly selected from complete population registration files. RESULTS In total 466 pediatric CNS tumor cases and 2,458 controls were available for analyses. We observed only few positive associations, namely, between CNS tumors and low birth weight [<2,500 g; odds ratio (OR), 1.73; 95% confidence interval (CI), 1.06-2.84], between ependymoma and maternal smoking during pregnancy (>10 cigarettes per day: OR, 4.71; 95% CI, 1.69-13.1), and between astrocytoma and exposure to wood preservatives (OR, 1.91; 95% CI, 1.22-3.01). CNS tumors were not associated with high birth weight, duration of breast feeding, maternal age at time of delivery, duration of gestation, previous fetal losses, paternal smoking during pregnancy, maternal alcohol consumption, the childs exposure to pesticides, maternal diagnostic X-ray examinations during pregnancy, X-ray examinations of the child, or exposure to residential magnetic fields. CONCLUSIONS Despite the large study population, we found only few factors that were associated with CNS tumors or one of the morphological subgroups. Therefore, our results suggest that aspects of the prenatal and neonatal period play only a minor role in the etiology of pediatric CNS tumors.

Childhood leukemia and electromagnetic fields: results of a population-based case-control study in Germany.

The investigation of an association between increased exposure toresidential extremely-low frequency elec-tromagnetic fields (ELF-EMF) andchildhood leukemia was part of a population-based case-control study carriedout between 1992 and 1995 in the northwestern part of Germany. A total of 129children with leukemia and 328 controls participated in the EMF-study.Exposure assessment comprised measurements of the magnetic field over 24hours in the childs bedroom at the residence where the child had been livingfor the longest period before the date of diagnosis, and spot measurements atall residences where the child had been living for more than one year. Themedian of the 24h-measurement in the childs bedroom was regarded as the mostvalid exposure variable. For children exposed to more than 0.2 μT, anelevated but not significant odds ratio (OR) was observed (OR = 3.2, 95percent confidence interval = 0.7-14.9). These figures are based on only fourleukemia cases and three controls since only 1.5 percent of the studypopulation was classified as highly exposed. Exploratory analyses revealedORs that were not statistically significantly increased for othercharacteristics of the magnetic field at varying cut-points. The results arecomparable with those from other studies. Although not statisticallysignificant, they may indicate a positive association between EMF andchildhood leukemia.

Combined risk estimates for two German population-based case-control studies on residential magnetic fields and childhood acute leukemia

From 1992 to 1996, we obtained electromagnetic field measurements in two population-based case-control studies on childhood leukemia in the northwestern part of Germany and in Berlin. Exposure assessment comprised residential 24-hour measurements and short-term measurements. We obtained 24-hour measurements for a total of 176 cases and 414 controls. We compared subjects exposed to median 24-hour measurements of 0.2 microT or more with those exposed to lower amounts. Multivariate regression analysis revealed an odds ratio of 2.3 (95% confidence interval = 0.8-6.7).

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.

Risk factors for neuroblastoma at different stages of disease. Results from a population-based case-control study in Germany

Neuroblastoma is one of the childhood cancers included in two recent population-based case-control studies in West Germany. Altogether, 183 children under the age of 8 with neuroblastoma diagnosed in 1988-1994 and 1785 control children sampled from population registration files participated. Information on potential risk factors was obtained from the childrens parents by a self-administered questionnaire and subsequent telephone interview. We observed positive associations with the use of oral contraceptives or other sex hormones during pregnancy (particularly with male offspring), a shorter gestational duration, lower birth weight, and maternal alcohol consumption during pregnancy. While the association with maternal use of oral contraceptives or sex hormones was strong for stages I/II (odds ratio 4.5, 95% confidence interval 1.2-16.5), the associations with shorter gestation duration (odds ratio 3.4, 95% confidence interval 1.7-6.7) as well as maternal alcohol consumption during pregnancy (>7 glasses/week odds ratio 5.2, 95% confidence interval 1.3-20.6) were observed only for the unfavourable advanced stages. It is notable that the associations in our study were either observed only for the advanced stages of disease or only for the less advanced stages, but not for both subgroups. This adds to evidence for the hypothesis that neuroblastoma consists of at least two distinct disease entities, which differ in clinical stage at the time of diagnosis.

Vitamin K and childhood cancer: a population based case-control study in Lower Saxony, Germany.

Abstract Objective: To confirm or refute a possible association of parenteral vitamin K prophylaxis and childhood cancer. Design: Population based case-control study. Comparison of vitamin K exposure in children with leukaemia or other common tumours with two control groups. Setting: State of Lower Saxony (north western part of Germany); case recruitment from the German childhood cancer registry. Subjects: 272 children with leukaemia, nephroblastoma, neuroblastoma, rhabdomyosarcoma, and tumours of the central nervous system diagnosed between 1 July 1988 and 30 June 1993; children were aged between 30 days and 15 years at diagnosis. 334 population based controls without diagnoses of cancer matched to the leukaemia cases for age and sex. Main exposure measures: Parenteral vitamin K prophylaxis (intramuscular and subcutaneous) versus oral and no vitamin K prophylaxis. Results: An association between parenteral vitamin K exposure and childhood cancer (leukae-mias and other tumours combined) could not be confirmed (odds ratio 1.04, 95% confidence interval 0.74 to 1.48). For leukaemias the observed odds ratio was only 0.98 (0.64 to 1.50) (comparison of leukaemia cases with local controls 1.24 (0.68 to 2.25); state controls 0.82 (0.50 to 1.36)). These odds ratios remained almost unchanged when several potential confounders were considered in the logistic regression model. Conclusions: This population based study adds substantial evidence that there is no association between parenteral vitamin K and childhood cancer. Key messages The study size was sufficient to detect a cancer risk of at least 1.55 The cumulative evidence from this and previous studies almost excludes an association of intramuscular vitamin K prophylaxis and childhood cancer

An extended study on childhood malignancies in the vicinity of German nuclear power plants.

Objectives: The study was performed to validate exploratory results obtained in a former study on the incidence rates of childhood malignancies in the vicinity of German nuclear power plants and to evaluate the confirmatory results of this previous study.Methods: Incidence rates near German nuclear installations were compared to rates in control regions based on the German Childhood Cancer Registry.Results: No exploratory result could be reproduced. This is also true for children with acute leukemia younger than 5 years who were living within a 5 km radius of an installation: an observed relative risk (RR) of 1.39 was not significantly increased (95 percent confidence interval CI: 0.69-2.57). Former confirmatory results could be confirmed again. A pooled analysis of both studies based on 2390 cases resulted in RR of 0.99 for all malignancies (CI: 0.91-1.07) and of 1.00 for acute leukemias (CI: 0.87-1.16) (children younger than 15 years of age living within a 15km radius).Conclusions: Results did not show significantly increased incidence rates for any subgroup with previously significant exploratory results. Therefore, it appears to be most likely that the previous results were just due to chance. Evaluating the previously confirmatory results with the combined data from the two study periods reassures that incidence rates are not increased in children younger than 15 years who are living within a 15 km radius, either for all malignancies or for acute leukemias. We conclude that at present, in Germany no further investigations of this kind are necessary.

High birth weight and other risk factors for Wilms tumour: results of a population-based case-control study

Abstract Wilms tumour, or nephroblastoma, is one of the childhood cancers included in two recent population-based case-control studies in West Germany. Altogether, 177 children under the age of 10 years with Wilms tumour diagnosed between 1988 and 1994 and 2006 control children sampled from population registration files participated. Information on potential risk factors was obtained from the parents using a questionnaire and by subsequent telephone interview. We found an association with a high birth weight >4000 g (odds ratio 1.58; 95% confidence interval 1.01–2.48), which was somewhat stronger for children aged 2 years or older. Findings for young maternal age at birth and certain parental occupationally related exposures were not reported by previous studies and thus may be chance findings. As opposed to previous studies, we failed to confirm associations with high parental age at birth, maternal coffee and tea consumption during pregnancy, and exposure to pesticides. Conclusion Based on this large population-based case-control study, high birth weight may play a role in the aetiology of Wilms tumour, but many risk factors previously suggested are of less importance.

Prevention of childhood leukemia by BCG vaccination in newborns? A population-based case-control study in Lower Saxony, Germany.

Data from a case-control study in Lower Saxony, Germany, were used to assess whether the risk for childhood cancer may be reduced by bacille Calmette-Guerin (BCG) vaccination in the neonatal period. There were 420 newly diagnosed childhood cancer cases from the German cancer registry and 613 controls eligible for this study. A mailed questionnaire was completed during a telephone interview with parents. Details on the perinatal history were abstracted from the birth charts by nurses blinded to the childrens case-control status. Complete information was available for 259 cases and for 323 controls. A total of 85% of the controls had been BCG vaccinated in the newborn period. The adjusted odds ratios for BCG vaccination were 0.90 (95% confidence interval; 0.51-1.61) for leukemia and 0.61 (95% confidence interval; 0.25-1.50) for other cancers. Based on these data the probability of a 50% or more reduction of more reduction of the cancer risk by BCG vaccination in the newborn period is small. The statistical power of this study, however, was not high enough to rule out a smaller, still relevant reduction in cancer risk.

Electromagnetic Fields and Childhood Leukemia: Pooled Analyses of Two German Population-Based Case-Control Studies

From 1992 to 1995 we conducted a population-based case-control study on residential magnetic fields and childhood leukemia in Lower Saxony, a region in northwestern Germany with 7.4 million inhabitants.1,2 Because of the rural character of this area, we detected elevated magnetic fields in only 1.5% of all dwellings. We therefore expanded the EMF-measurements to an ongoing case-control study on childhood leukemia in the capital of Germany, Berlin. We applied the same methods of exposure assessment, intending to pool the data of the two studies and to calculate combined risk estimates.3