EUROCLUS
Clustering of Childhood Leucaemia in Europe
 

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.

ALEXANDER, FE., BOYLE, P., CARLI, PM., COEBERGH, JW., DRAPER, GJ., EKBOM, A., LEVI, F., McKINNEY, PA., McWHIRTER, W., MICHAELIS, J., PERIS-BONET, R., PETRIDOU, E., POMPE-KIRN, V., PLISKO, I., PUKKALA, E., RAHU, M., STORM, H., TERRACINI, B., VATTEN, L., WRAY, N
Spatial clustering of childhood leukaemia: summary results from the EUROCLUS project. Br-J-Cancer. 1998 Mar; 77(5): 818-24
 
 
 

The EUROCLUS project included information on residence at diagnosis for 13351 cases of childhood leukaemia diagnosed in the period 1980-89 in defined geographical regions in 17 countries. A formal algorithm permits identification of small census areas as containing case excesses. The present analysis examines spatial-temporal patterns of the cases (n = 970) within these clustered areas. The objectives were, first, to compare these results with those from an analysis conducted for UK data for the period 1966-83, and, second, to extend them to consider infant leukaemias. A modification of the Knox test investigates, within the small areas, temporal overlap between cases in a subgroup of interest at a putative critical time and all other cases at any time between birth and diagnosis. Critical times were specified in advance as follows: for cases of acute lymphoblastic leukaemia aged 2-4 years, the 18-month period preceding diagnosis; for cases of total leukaemia aged 5-14 years, 1 year before to 1 year after birth; and for infant cases (diagnosed < 1 year), 1 year before to 6 months after birth. Each of the analyses found evidence of excess space-time overlap compared with that expected; these were 10% (P = 0.005), 15% (P= 0.0002) and 26% (P= 0.03) respectively. The results are interpreted in terms of an infectious origin of childhood leukaemia.

ALEXANDER, FE., BOYLE, P., CARLI, PM., COEBERGH, JW., DRAPER, GJ., EKBOM, A., LEVI, F., McKINNEY, PA., McWHIRTER, W., MAGNANI, C., MICHAELIS, J., OLSEN, JH., PERIS-BONET, R., PETRIDOU, E., PUKKALA, E., VATTEN, L.
Spatial temporal patterns in childhood leukaemia: further evidence for an infectious origin. EUROCLUS project. Br-J-Cancer. 1998 Mar; 77(5): 812-7

Many reports of clusters of childhood leukaemia have been published, but their interpretation is unclear. It remains uncertain as to whether the distribution of cases shows a general tendency to cluster, and this suggests a role for epidemics of common infections or environmental hazards in leukaemogenesis. A European collaborative study of childhood leukaemia (the EUROCLUS project) is underway, and its aims, rationale, protocol and methodology are summarized. Over 12 000 cases of childhood leukaemia diagnosed in 1980-89 in 13 countries will be available for analysis. The Potthoff-Whittinghill test which is used has high statistical power to detect clustering within small census areas and which involve at least 15 % of all cases. These results are robust to differences in distributions of small area size between countries. Power calculations have been performed for Norway, Scotland and Sweden for each of four alternative models of clustering. The project should identify whether there is a general tendency for cases of childhood leukaemia (particularly young cases of acute lymphoblastic leukaemia) to cluster within small areas.

ALEXANDER, F.E., WRAY, N., BOYLE, P. et al.
Clustering of childhood leukaemia: a European study in progress. Journal of Epidemiology and Biostatistics 1, 13-24, 1996.