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Br J Cancer. 2012 Sep 25;107(7):1163-8. doi: 10.1038/bjc.2012.402. Epub 2012 Sep 6.

An examination, with a meta-analysis, of studies of childhood leukaemia in relation to population mixing.

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Cancer Epidemiology Unit, University of Oxford, Richard Doll Building, Headington, Oxford OX3 7LF, UK.

Erratum in

  • Br J Cancer. 2013 Mar 19;108(5):1222.



Marked influxes of people into rural areas, termed rural population mixing (PM), have been associated with excesses of childhood leukaemia (CL), consistent with mini-epidemics of a mainly immunising, subclinical infection to which CL is a rare response. For such situations of rural PM would promote contacts between infected and susceptible individuals, the latter tending to have a higher than average prevalence in rural or isolated areas. Confusion has arisen from some workers applying the term PM to non-rural situations lacking known recent change.


Available PM studies using the original definition of influxes were examined, a meta-analysis carried out of studies of CL in relation to exposure to high levels of rural PM, and also a detailed analysis by age group.


The meta-analysis of 17 studies shows a significant CL excess in association with rural PM: overall relative risk (RR) at ages 0-14: 1.57; 95% confidence interval 1.44-1.72; at 0-4 years 1.72 (1.54-1.91). This contrasts with the absence of an excess of CL in similarly exposed urban areas (RR 1.00; 0.93-1.07), pointing to a high level of immunity there. The mixed results of studies using other definitions of PM were summarised. The excess associated with rural PM below age 2 years (RR 1.51; 1.17, 1.92) was not appreciably different from that at later childhood ages.


Much of the inconsistency among studies ostensibly about CL and PM reflects the use of definitions other than that originally proposed. The broad similarity of the CL excess below age 2 with that at older childhood ages is inconsistent with the Greaves' delayed infection hypothesis, since any infection underlying the former is difficult to consider as delayed.

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