Cancer Epidemiology Unit, Gibson Building, Radcliffe Infirmary, University of Oxford, Oxford OX2 6HE, United Kingdom
Population mixing was recently suggested as a possible explanation for the striking cluster of cases of childhood leukemia that occurred in Fallon, Nevada, in 20002001 (1). Law et al. (2) sought to test the plausibility of this suggestion by investigating whether population mixing played any part in the production of the disease in a large case-control study of childhood cancer in the United Kingdom. They concluded that it did not and consequently questioned the validity of the hypothesis. It may be doubted, however, whether their findings have any material bearing on the issue, since their definition of population mixing differs greatly from what was meant when population mixing was proposed in the late 1980s as a cause of the disease (3, 4).
The fundamental idea was that in most cases childhood leukemia is a rare response to a common but unidentified infection and that a localized epidemic of this underlying infection might occur, as epidemics of other such diseases have occurred, when a large group of peoplemany with urban backgrounds and therefore exposed to a wide variety of infectionsmoves into a sparsely populated area where a substantial proportion of the population has not been so exposed and is therefore susceptible to infection. Studies of large-scale urban-rural mixing in rural areas of the United Kingdom (all associated with population increase and often crowding) during the years 19411988, as well as other studies conducted elsewhere, have shown significant excesses of childhood leukemia (5, 6). In exceptional circumstances, it might be possible to detect excesses of the disease from unusual population movements in urban areas (7), but the essence of the concept was the influx of infected persons into a previously sparsely populated area. In contrast, the data of Law et al. (2) were largely derived from the movements of people within and between urban areas as indicated by a single census, without necessarily any marked increase in population. Large numbers of susceptible persons were unlikely to be found in such areas, and consequently the circumstances required for the occurrence of epidemics did not exist. Indeed, there is no indication that any example of rural population mixing comparable to the situations previously studied (5, 6) was covered by Law et al. What is surprising is their chosen approach, given the previous announcement that the case-control study from which they obtained their data was planned in order to investigate childhood leukemia "in rural areas of marked population mixing" (8, p. 1074).
Fallon, Nevada, is a small town in a large desert area near the Fallon naval air base, at which the intake of trainees had been increased just prior to 2000 from 20,000 per year to 50,000 per yearaspects that were not mentioned by Law et al. (2). Under these circumstances, the relevance of population mixing is clear, and it is not surprising that the expert panel which examined the Fallon childhood leukemia cluster identified population mixing as a possible explanation (1). It is notable that this is not the only example of increases in military personnel in rural areas being followed by excesses of childhood leukemia (5, 6).
The overall evidence for an infective basis of childhood leukemia and for a role of unusual rural population mixing is compelling (9). The study by Law et al. (2) does not materially detract from this conclusion or from the plausibility of the concept of population mixing as an explanation for the Fallon cluster.
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