Space-time clustering of childhood leukaemia in Greece: evidence supporting a viral aetiology

Abstract

SummaryThe method introduced by Knox for evaluation of space-time clustering has been applied to 872 cases of childhood (0-14 year old) leukaemia diagnosed in Greece over the 10 year period 1980-89. Greek towns are characterised by substantial population mixing due to internal migration, whereas there is relative isolation in mountainous rural areas. Predetermined space (5 km) and time (1 year) limits were used on the basis of previous reports in order to define the clustering cell. There is highly significant evidence for clustering of childhood leukaemia in Greece as a whole, the observed number of pairs that are close in both space and time exceeding the expected number by 5.2% (P= 0.004). The excess is particularly evident for leukaemia cases in 0 to 4-year-old children, among whom the observed number of pairs that are close in both space and time exceeded the expected number by 9.4% (P= 0.004). There is no evidence of space-time clustering for leukaemia cases older than 5 years. The overall pattern is descriptively similar in urban and semiurban areas and is especially marked for acute lymphoblastic leukaemia at the childhood peak ages (2-4 years) with an excess of 19% (P=0.0006). In the rural population there is evidence for clustering of cases belonging to older and broader age groups, a phenomenon compatible with a delay in the development of herd immunity against putative infectious aetiological agents. The findings of the present study provide support for the hypothesis that a substantial proportion of cases of childhood leukaemia may arise as a rare sequel to exposure to an agent or agents, most probably viral in nature.

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).…”

The Seascale cluster: a probable explanation

“…The findings in these and other studies by other workers (Langford, 1991;Petridou et al, 1996;Stiller and Boyle, 1996;Alexander et al, 1997) make a formidable case. It was dismissed by COMARE (1996), however, as an adequate explanation on the grounds that the hypothesis could not account for such a great increase in risk as that observed in Seascale over a prolonged period.…”

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.…”