Space-time clustering of childhood acute lymphoblastic leukaemia: indirect evidence for a transmissible agent

Abstract

Despite numerous anecdotal reports of small clusters of cases of childhood leukaemia, formal statistical analyses have yielded equivocal results (Linet, 1985). Incidence data from the UK national children's tumour registry (CCRG) for 1968-1983 have recently become available for small area analyses by location at diagnosis (OPCS, 1991). Extensive analyses using a variety of methodologies have shown consistent, though weak, evidence of the occurrence of both spatial clustering and space-time interactions. Results from one of these analyses (Alexander, 1991) are now extended to test specific prior hypotheses generated by an independent case-control study (Alexander et. al., 1992). These suggested that transmission of a specific, though unknown, agent (Z) plays some role in the development of childhood acute lymphoblastic leukaemia (ALL) with the times when children are susceptible to infection differing by age-of-onset and hence subtype of ALL. For cases with older onset (aged 5 years and over) it was suggested that persistent infection may have been established in utero or early infancy and, now, formal testing of appropriate space-time interactions provide indirect confirmation of this (P = 0.0002). More recent exposure to Z may contribute to ALL in the childhood peak years (Alexander et. al., 1992) but the confirmation provided here is less strong (P = 0.05). The results afford new impetus to a search for a transmissible aetiologic agent or agents; these need not be rare and the results should not be interpreted as evidence for direct case to case transmission.