An infectious aetiology for childhood brain tumours? Evidence from space–time clustering and seasonality analyses

Abstract

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 ...

Childhood solid tumours in relation to infections in the community in Cumbria during pregnancy and around the time of birth

“…As many comparisons were made, this may be a consequence of multiple hypothesis testing. However, several factors support a genuine association: the effect was more marked in younger children and was consistent across several types of infection, and other studies have reported evidence of an infective aetiology of these tumours (Linet et al, 1996;Linos et al, 1998;Fear et al, 2001;McNally et al, 2002).…”

“…A cohort study of children born during a period of over 50 years, found space -time clustering of pilocytic astrocytoma and ependymoma in children aged 0 -4 years, suggesting that pre-natal or peri-natal exposure to infection may be a risk factor for these tumours (McNally et al, 2002). Although our study did not have enough cases to analyse by specific type, the young age distribution and preponderance of astrocytomas and ependymomas among children highly exposed to peri-natal infections were consistent with the findings of McNally et al (2002).…”

“…A cohort study of children born during a period of over 50 years, found space -time clustering of pilocytic astrocytoma and ependymoma in children aged 0 -4 years, suggesting that pre-natal or peri-natal exposure to infection may be a risk factor for these tumours (McNally et al, 2002). Although our study did not have enough cases to analyse by specific type, the young age distribution and preponderance of astrocytomas and ependymomas among children highly exposed to peri-natal infections were consistent with the findings of McNally et al (2002). Some epidemiological studies have provided tentative direct evidence of the involvement of maternal viral infections in childhood brain tumours (Linos et al, 1998;Fear et al, 2001), while others have not found such an association (Bunin et al, 1994;McKinney et al, 1999).…”

“…However, subsequent studies did not confirm this association and interest in this area waned (Leck and Steward, 1972;Curnen et al, 1974;Randolph and Heath, 1974). However, recent epidemiological studies have suggested that exposure to infections before or around birth may be associated with the risk of solid tumours, in particular brain tumours, in children (Linet et al, 1996;Linos et al, 1998;McKinney et al, 1999;Fear et al, 2001;McNally et al, 2002). In addition, it has been suggested that JC virus has a role in the aetiology of brain tumours (Khalili, 2001).…”

Childhood solid tumours in relation to population mixing around the time of birth

“…However, we subsequently reported an association between exposure around birth to high levels of population mixing and a lower risk of brain and spinal tumours and a possible association between parental migration and a higher risk of neuroblastoma (Dickinson et al, 2002b). Recent epidemiological studies have suggested that exposure to infections before or around birth may be associated with the risk of brain tumours in children (Linet et al, 1996;Linos et al, 1998;McKinney et al, 1999;Fear et al, 2001;McNally et al, 2002). In addition, it has been suggested that JC virus has a role in the aetiology of brain tumours (Khalili, 2001).…”