To investigate whether infections or other environmental exposures may be involved in the aetiology of childhood central nervous system tumours, we have analysed for space -time clustering and seasonality using population-based data from the North West of England for the period 1954 to 1998. Knox tests for space -time interactions between cases were applied with fixed thresholds of close in space, 55 km, and close in time, 51 year apart. Addresses at birth and diagnosis were used. Tests were repeated replacing geographical distance with distance to the Nth nearest neighbour. N was chosen such that the mean distance was 5 km. Data were also examined by a second order procedure based on K-functions. Tests for heterogeneity and Edwards' test for sinusoidal variation were applied to examine changes of incidence with month of birth or diagnosis. There was strong evidence of space -time clustering, particularly involving cases of astrocytoma and ependymoma. Analyses of seasonal variation showed excesses of cases born in the late Autumn or Winter. Results are consistent with a role for infections in a proportion of cases from these diagnostic groups. Further studies are needed to identify putative infectious agents. British Journal of Cancer (2002) In the developed world central nervous system (CNS) tumours are the second most common group of malignancies in children (Parkin et al, 1998). The aetiology of childhood CNS tumours is far from clear. Heritable syndromes are the only established causes, but these account for a minority of cases (Bondy et al, 1991). A number of statistically significant associations with certain exposures have been noted from case -control studies, including: consumption of cured meats/fish during pregnancy; insecticides/pesticides; farm residence; and electro-magnetic fields (Little, 1999). However, there is inconsistency between studies, and relative risks were all small.There has been much speculation about the role of certain viruses in human brain tumours (Barbanti-Brodano et al, 1997), but very few epidemiological studies have addressed the possibility of an infectious aetiology. If infections are involved in the aetiology of childhood brain tumours, the distribution of cases may be predicted to exhibit space -time clustering. Space -time clustering is said to occur when excess numbers of cases are observed within various small geographical locations, but only at limited points in time. The presence of seasonal variation would also provide evidence for an infectious aetiology. We have therefore examined incidence data from the Manchester Children's Tumour Registry (MCTR) for presence of space -time clustering and seasonal variation. This registry is population based with consistently high ascertainment and contains verified diagnostic data over a 45 year period (Birch, 1988). The aims of our study were to test predictions of space -time clustering and seasonal patterns which might arise as a result of infectious mechanisms and to distinguish between exposures around the times of birth ...

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The aetiology of most childhood solid tumours (other than central nervous system [CNS] tumours) is unclear. To investigate whether certain environmental exposures may be involved, we have analysed for space-time clustering using population-based data from North West England for the period 1954 -98. Knox tests for space-time interactions between cases were applied with fixed thresholds of close in space, <5 km, and close in time, <1 year apart. Addresses at birth and at diagnosis were used. Tests were repeated replacing geographical distance with distance to the Nth nearest neighbour. N was chosen such that the mean distance was 5 km. The aetiology of solid tumours, other than central nervous system tumours (non-CNS solid tumours) in children is far from clear. There are 2 possible general mechanisms: genetic susceptibility and environmental exposures. The very early age of onset and the embryonal nature of many non-CNS solid tumours of childhood suggest a prenatal origin for most, if not all, of these tumours and genetic factors are likely to be important. 1 Mutations in a number of tumour suppressor genes confer increased risk for certain embryonal tumours but inherited single gene defects would account for a small minority of cases only. De novo germline mutations in affected children have been reported, 2-7 however, and the possibility that parental pre-conceptional exposures might give rise to such mutations should be considered. Although it is likely that high penetrance genes play a role in a minority of cases, other low penetrance genes and gene-environment interactions may be important and pre-or post-natal exposure of a genetically susceptible child might also be a factor.A number of statistically significant associations between certain parental occupations or occupational exposures and childhood non-CNS solid tumour risk have been reported. Associations with parental exposures may indicate parental germ cell mutation or transplacental exposure of the fetus. These parental associations include: exposure to pesticides, metals, chemicals, solvents, petroleum products, paints, pigments, plastic and resin fumes and maternal use of sex hormones before or during the index pregnancy. 8 There is inconsistency, however, between studies and relative risks for the noted associations were all small.Certain environmental agents, including industrial and traffic pollution, pesticides and infections, are likely to occur at localised geographical points at certain times or time periods. If such agents are involved in the aetiology of specific childhood non-CNS solid tumours, pre-conceptionally, pre-natally or post-natally, the distribution of cases may exhibit space-time clustering. Space-time clustering is said to occur when excess numbers of cases are observed within various small geographical locations, but only at limited points in time. Such clustering should occur amongst particular diagnostic types sharing a common aetiology.There have been a number of studies that have applied formal statistical methods 9,10 t...