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Childhood acute lymphoblastic leukaemia in relation to population mixing around the time of birth in South Hungary

To the Editor: The study by Nyári et al. [1] in this issue of Pediatric Blood & Cancer investigates the association between high levels of community mixing around the time of birth and acute lymphoblastic leukaemia (ALL) in children diagnosed before their fifth birthday. The data were based on high-quality information from Hungary, which was of interest as population mixing has not been investigated extensively across Europe. Unfortunately, the authors have not provided an appropriate interpretation for the studies by Parslow et al. [2] and Law et al. [3]. Table IV suggested that the findings reported no relationship between population mixing and the risk of ALL. Parslow et al. [2] reported that the incidence of all childhood leukaemias was significantly lower in areas of high population mixing and higher in areas of low population mixing. Law et al. [3] reported elevated risks of ALL in areas of low mixing diversity. One possible reason for the confusion may be the simplified way in which the results from previous studies were presented. In much the same way aP-value presented on its own gives no information on the direction and precision of an association, a simple ‘yes/no’ answer as to whether a study reported a relationship between population mixing and risk of leukaemia is of limited value. For example, the study by Koushik et al. [4] reported population growth was associated with an increased incidence of ALL in rural areas, although the risk decreased in urban areas. Alexander et al. [5] reported that in areas of high population growth, incidence was not significantly elevated from that in other areas, but there was evidence of spatial clustering in these areas. These results cannot be readily deduced from Table IV. A more useful comparison could be obtained by a ‘Forest plot’ such as the one presented in Law et al. [3]. The size and direction of the relationship, the precision, and the sample size of each study would therefore be comparable in this way. Furthermore, Parslow et al. [2] did not investigate population mixing in isolated communities as suggested by the authors. The analysis was performed on children from 532 electoral wards in Yorkshire. The diversity of the origins of incoming migrants was used as a measure of population mixing instead of stratifying for those originating from rural areas. Additionally, this study was not a cohort design but ecological in nature. The study by Alexander et al. [6] was also an ecological analysis and did not specifically examine the relationship between population mixing and risk of leukaemia. It is worth emphasizing that the definition of population mixing and the measures used to calculate it vary between investigations. Some studies may not be directly comparable with others because of this issue. Nyári et al. [1] used the proportion of migrants as their measure. Other measures used in previous investigations include migration diversity, migration volume, population growth, and qualitative measures. A consensus needs to be reached on a definitive measure of population mixing to further investigate the association with the etiology of childhood leukaemia.