Clustering of childhood leukaemia in Hong Kong: association with the childhood peak and common acute lymphoblastic leukaemia and with population mixing

Abstract

Summary Incidence data of childhood leukaemia (CL) in Hong Kong (1 984-90) have been analysed for evidence of variation between small areas. All cases (n=261) were classified by morphological cell type, with the majority (n=205) being acute lymphoblastic leukaemia (ALL), and haematological review has permitted immunophenotypic classification for 73% of these. The data have been examined for evidence of spatial clustering within small census areas (TPUs) and for association with population mixing, with attention focused on those subgroups (especially the childhood peak of ALL -taken here to be diagnoses in children from 24 months up to the seventh birthday -and common ALL) which, it has been hypothesized, may be caused by unusual patterns of exposure and response to common infections. For the whole of Hong Kong, there was evidence of spatial clustering of ALL at ages 0-4 years (P = 0.09) and in the childhood peak (P<0.05). When these analyses were restricted to TPUs where extreme population mixing may have occurred, overall incidence was elevated and significant evidence of clustering was found for ALL (P<0.007) at these ages and for the common ALL in the childhood peak (P= 0.032). Replication of the analyses for subsets of leukaemia that were not dominated by the childhood peak of ALL found no evidence of clustering. This is the first investigation of an association between population mixing and childhood leukaemia in Asia and the first to include clustering and to consider particular subsets. The results are supportive of the 'infectious' aetiology hypothesis for subsets of childhood leukaemia, specifically common ALL in the childhood peak.

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

“…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).…”

“…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). Properties of rural areas include low population density, relative isolation, limited commuting or visitation from other areas, etc, although specific definitions vary by county.…”

High-contact paternal occupations, infection and childhood leukaemia: five studies of unusual population-mixing of adults

“…Such situations would be conducive to mini-epidemics of an underlying infection to which leukaemia is an uncommon response and, in a large series of examples studied, significant excesses of childhood leukaemia have been found (Kinlen, 1988;Kinlen et al, 1990Kinlen et al, , 1993aKinlen et al, , 1995Langford, 1991;Kinlen and John, 1994;Petridou et al, 1996;Stiller and Boyle, 1996;Alexander et al, 1997). These community-based findings make a persuasive case for an infective basis for childhood leukaemia.…”

Childhood leukaemia and population movements in France, 1990–2003

“…Besides, the population variations between the census years were so skewed on the commune scale that this measure could not be considered in the present study. Several other studies have shown that areas with high proportions of migrants or marked changes in population were at a significantly higher risk of CL than other areas (Langford, 1991;Stiller and Boyle, 1996;Alexander et al, 1997;Dickinson et al, 2002;Labar et al, 2004;Nyari et al, 2006;Rudant et al, 2006). In the UK, Dickinson et al found an increased risk of disease only in urban census wards.…”