Ionising radiation and childhood leukaemia revisited.

Increased incidences of childhood acute leukaemia were noted among survivors of the atomic bombings of Hiroshima and Nagasaki. In Western societies, Childhood Acute Lymphoblastic Leukaemia has a distinct epidemiology peaking at 3 years old. Exposure to ionising radiation is an established hazard but it is difficult to gauge the precise risk of less than 100 mSv. Since 1983 significant leukaemia incidences have been reported among families residing near nuclear installations. The target cells (naïve neonatal lymphocytes) get exposed to multiple xenobiotic challenges and undergo extraordinary proliferation and physiological somatic genetic change. Population movements and ionising radiation are considered taking account of updated understanding of radiation biology, cancer cytogenetics and immunological diversity. Double Strand Breaks in DNA arise through metabolic generation of Reactive Oxygen Species, and nearly always are repaired; but mis-repairs can be oncogenic. Recombinant Activating Gene enzymes in rapidly dividing perinatal pre-B lymphocytes being primed for antibody diversity are targeted to Signal Sequences in the Immunoglobulin genes. off target pseudo-sequences may allow RAG enzymes to create autosomal DSBs which, when mis-repaired, become translocated oncogenes. Immunogens acting by chance at crucial stages may facilitate this. In such circumstances, oncogenic DSBs from ionising radiation are less likely to be significant.

Can changes in population mixing and socio-economic deprivation in Cumbria, England explain changes in cancer incidence around Sellafield?

Previously excesses in incident cases of leukaemia and non-Hodgkin lymphoma have been observed amongst young people born or resident in Seascale, Cumbria. These excesses have not been seen more recently. It is postulated that the former apparent increased risk was related to 'unusual population mixing', which is not present in recent years. This study investigated changes in measures of population mixing from 1951-2001. Comparisons were made between three specified areas. Area-based measures were calculated (migration, commuting, deprivation, population density). All areas have become more affluent, although Seascale was consistently the most affluent. Seascale has become less densely populated, with less migration into the ward and less diversity with respect to migrants' origin. There have been marked changes in patterns of population mixing throughout Cumbria. Lesser population mixing has been observed in Seascale in recent decades. Changes in pattern and nature of population mixing may explain the lack of recent excesses.

Population mixing and incidence of cancers in adolescents and young adults between 1990 and 2013 in Yorkshire, UK.

PURPOSE: Epidemiological evidence suggests a role for an infectious etiology for cancers in teenagers and young adults (TYAs). We investigated this by describing associations between infection transmission using the population mixing (PM) proxy and incidence of cancers in TYAs in Yorkshire, UK. METHODS: We extracted cancer cases from the Yorkshire Specialist Register of Cancer in Children and Young People from 1990 to 2013 (n = 1929). Using multivariable Poisson regression models (adjusting for effects of deprivation and population density), we investigated whether PM was associated with cancer incidence. We included population mixing-population density interaction terms to examine for differences in effects of PM in urban and rural populations. RESULTS: Nonsignificant IRRs were observed for leukemias (IRR 1.20, 95% CI 0.91-1.59), lymphomas (IRR 1.09, 95% CI 0.90-1.32), central nervous system tumors (IRR 1.06, 95% CI 0.80-1.40) and germ cell tumors (IRR 1.14, 95% CI 0.92-1.41). The association between PM and cancer incidence did not vary in urban and rural areas. CONCLUSIONS: Study results suggest PM is not associated with incidence of cancers among TYAs. This effect does not differ between rural and urban settings.

Temporal association between childhood leukaemia and population growth in Swiss municipalities.

The population mixing hypothesis proposes that childhood leukaemia (CL) might be a rare complication of a yet unidentified subclinical infection. Large population influxes into previously isolated rural areas may foster localised epidemics of the postulated infection causing a subsequent increase of CL. While marked population growth after a period of stability was central to the formulation of the hypothesis and to the early studies on population mixing, there is a lack of objective criteria to define such growth patterns. We aimed to determine whether periods of marked population growth coincided with increases in the risk of CL in Swiss municipalities. We identified incident cases of CL aged 0-15 years for the period 1985-2010 from the Swiss Childhood Cancer Registry. Annual data on population counts in Swiss municipalities were obtained for 1980-2010. As exposures, we defined (1) cumulative population growth during a 5-year moving time window centred on each year (1985-2010) and (2) periods of 'take-off growth' identified by segmented linear regression. We compared CL incidence across exposure categories using Poisson regression and tested for effect modification by degree of urbanisation. Our study included 1500 incident cases and 2561 municipalities. The incident rate ratio (IRR) comparing the highest to the lowest quintile of 5-year population growth was 1.18 (95 % CI 0.96, 1.46) in all municipalities and 1.33 (95 % CI 0.93, 1.92) in rural municipalities (p value interaction 0.36). In municipalities with take-off growth, the IRR comparing the take-off period (>6 % annual population growth) with the initial period of low or negative growth (<2 %) was 2.07 (95 % CI 0.95, 4.51) overall and 2.99 (1.11, 8.05) in rural areas (p interaction 0.52). Our study provides further support for the population mixing hypothesis and underlines the need to distinguish take-off growth from other growth patterns in future research.

Population mixing and the risk of childhood leukaemia in Switzerland: a census-based cohort study.

Childhood leukaemia (CL) may have an infectious cause and population mixing may therefore increase the risk of CL. We aimed to determine whether CL was associated with population mixing in Switzerland. We followed children aged <16 years in the Swiss National Cohort 1990-2008 and linked CL cases from the Swiss Childhood Cancer Registry to the cohort. We calculated adjusted hazard ratios (HRs) for all CL, CL at age <5 years and acute lymphoblastic leukaemia (ALL) for three measures of population mixing (population growth, in-migration and diversity of origin), stratified by degree of urbanisation. Measures of population mixing were calculated for all municipalities for the 5-year period preceding the 1990 and 2000 censuses. Analyses were based on 2,128,012 children of whom 536 developed CL. HRs comparing highest with lowest quintile of population growth were 1.11 [95 % confidence interval (CI) 0.65-1.89] in rural and 0.59 (95 % CI 0.43-0.81) in urban municipalities (interaction: p = 0.271). Results were similar for ALL and for CL at age <5 years. For level of in-migration there was evidence of a negative association with ALL. HRs comparing highest with lowest quintile were 0.60 (95 % CI 0.41-0.87) in urban and 0.61 (95 % CI 0.30-1.21) in rural settings. There was little evidence of an association with diversity of origin. This nationwide cohort study of the association between CL and population growth, in-migration and diversity of origin provides little support for the population mixing hypothesis.