Spatial temporal patterns in childhood leukaemia: further evidence for an infectious origin

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Summary 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 13 351 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.

Section: Discussionsupporting

confidence: 82%

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

Alexander

Boyle²,

Carli³

et al. 1998

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“…Kinlen and colleagues have studied childhood leukaemia in a wide range of situations in which isolated populations were exposed to a large influx of outsiders or other sources of infectious agents (Kinlen et al, 1990(Kinlen et al, , 2002Kinlen and Stiller, 1993;Kinlen and John, 1994;Kinlen and Petridou, 1995;Kinlen, 1993Kinlen, , 1997Kinlen, , 2000aKinlen and Balkwill, 2001;Kinlen and Bramald, 2001). Other investigators have undertaken similar investigations in other situations and in other countries and obtained largely similar results (Langford, 1991;Roman et al, 1994;Dockerty et al, 1996;Petridou et al, 1996;Stiller and Boyle, 1996;Alexander et al, 1997Alexander et al, , 1998aDickinson and Parker, 1999;Fear et al, 1999;Birch et al, 2000;Koushik et al, 2001;Boutou et al, 2002;Dickinson et al, 2002aDickinson et al, , 2002bDickinson and Parker, 2002;Parslow et al, 2002). The effect is seen most strongly for ALL at ages 0 -4 and in the most rural areas (Kinlen et al, 1990(Kinlen et al, , 2002Stiller and Boyle, 1996;Alexander et al, 1997;Koushik et al, 2001;Kinlen and Balkwill, 2001;Kinlen and Bramald, 2001).…”

Section: Discussionmentioning

confidence: 59%

Childhood leukaemia incidence and the population mixing hypothesis in US SEER data

Wartenberg¹,

Schneider

Brown

2004

We evaluated the infectious aetiology hypothesis of childhood leukaemia that rapid population influx into rural areas is associated with increased risk. Using data from the US SEER program, we found that in changes in rural county population sizes from 1980 to 1989 were associated with incidence rates for childhood acute lymphocytic leukaemia (ALL). The observed associations were strongest among children 0 -4 years of age, born in the same state as diagnosis, in extremely rural counties, and when counties adjacent to nonrural counties were excluded. Similar analyses for brain and central nervous system (CNS) cancer in children, a disease less linked to this infectious hypothesis, provide evidence against methodologic bias. Similar evaluations for other decades were not meaningful due to limited sample sizes and, perhaps, increased population mobility.

“…The results indicate statistically significant evidence of clustering of ALL in the childhood peak years as well as ALL at older age of onset, although the magnitude is small (Alexander et al, 1998). …”

Section: Discussionmentioning

confidence: 89%

Evidence of space–time clustering of childhood acute lymphoblastic leukaemia in Sweden

Gustafsson

Carstensen

1999

SummaryWe have examined 645 recorded cases of childhood acute lymphatic leukaemia (ALL) in Sweden during 1973-89 to identify space-time clustering by using the close-pair method of Knox. The records included date of birth and of diagnosis as well as addresses at birth and at diagnosis. There was a significant excess of case pairs close in date of birth and place of birth in the 5-to 15-year age group.