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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.