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Background: We summarise the work of the Childhood Cancer Research Group, particularly in relation to the UK National Registry of Childhood Tumours (NRCT)., Methods: The Group was responsible for setting up and maintaining the NRCT. This registry was based on notifications from regional cancer registries, specialist children's tumour registries, paediatric oncologists and clinical trials organisers. For a large sample of cases, data on controls matched by date and place of birth were also collected., Results: Significant achievements of the Group include: studies of aetiology and of genetic epidemiology; proposals for, and participation in, international comparative studies of these diseases and on a classification system specifically for childhood cancer; the initial development of, and major contributions to, follow-up studies of the health of long-term survivors; the enhancement of cancer registration records by the addition of clinical data and of birth records. The Group made substantial contributions to the UK government's Committee on Medical Aspects of Radiation in the Environment., Conclusion: An important part of the ethos of the Group was to work in collaboration with many other organisations and individuals, both nationally and internationally: many of the Group's achievements described here were the result of such collaborations.

Background: High doses of ionising radiation are a known cause of childhood cancer and great public and professional interest attaches to possible links between childhood cancer and lower doses, particularly of man-made radiation. This paper describes work done by the Childhood Cancer Research Group (CCRG) on this topic METHODS: Most UK investigations have made use of the National Registry of Childhood Tumours and associated controls. Epidemiological investigations have included national incidence and mortality analyses, geographical investigations, record linkage and case-control studies. Dosimetric studies use biokinetic and dosimetric modelling., Results: This paper reviews the work of the CCRG on the association between exposure to ionising radiation and childhood cancer, 1975-2014., Conclusion: The work of CCRG has been influential in developing understanding of the causes of 'clusters' of childhood cancer and the risks arising from exposure to ionising radiation both natural and man-made. Some clusters around nuclear installations have certainly been observed, but ionising radiation does not seem to be a plausible cause. The group's work has also been instrumental in discounting the hypothesis that paternal preconception irradiation was a cause of childhood cancers and has demonstrated an increased leukaemia risk for children exposed to higher levels of natural gamma-ray radiation.

Background: Concern about the risk of leukaemia in children living near nuclear power plants (NPPs) persists. Previous British analyses have been area based and consequently thought to be less effective than case-control studies., Methods: Cases of childhood leukaemia and non-Hodgkin lymphoma (LNHL) born and diagnosed in Great Britain between 1962 and 2007, with matched cancer-free controls, were analysed by logistic regression to estimate the risk of residential proximity at birth and diagnosis to the nearest NPP, adjusting for relevant variables., Results: For 9821 children with LNHL under the age of 5 years, the estimated extra risk associated with residential proximity to an NPP at birth was negative-interpolated Odds Ratio (OR) at 5 km was 0.86 (0.49-1.52). The comparison of 10 618 children with LNHL under five with 16 760 similarly aged children with other cancers also gave a negative estimate of the extra risk of residential proximity at diagnosis-interpolated OR at 5 km was 0.86 (0.62-1.18)., Conclusion: Our results show little evidence of an increase in risk of LNHL to children aged under 5 years from living in the vicinity of an NPP. Risk estimates are incompatible with comparable ones published in a recent German case-control study.

We investigated whether living close to railway lines is a risk factor for childhood leukaemia and non-Hodgkin's lymphoma in electoral wards in England and Wales, 1966-1987. The national rail network, 1966-1987, was digitised and the numbers of cases in each ward were related to two measures of environmental exposure to railways: a proximity and a density function, contributions to these functions being weighted by the frequency of use and time in use of each stretch of railway. Poisson regression was used to derive rate ratios in relation to these measures of exposure to railways, both unadjusted and adjusted for population mixing. We found no association between risk of leukaemia and railway proximity (unadjusted rate ratio for trend from the lowest to the median value=1.006, 95% CI: 0.998 - 1.013, P=0.14) and a very small association with railway density, of marginal statistical significance (rate ratio for trend=1.001, 95% CI: 1.000 - 1.003, P=0.05). This effect depended on two deprived, urban wards with high railway density and high population mixing and became nonsignificant (P=0.09) after allowing for population mixing. The very weak association between railway density and risk of childhood leukaemia is likely to be a consequence of the association between population mixing and proximity to railways in very deprived, urban wards.

We found an increased risk of childhood leukaemia with higher levels of inward migration, particularly from outside the region (rate ratio=1.9, 95%CI: 1.2-2.9, P<0.01). This significant effect was observed only in urban areas, although a marked but non-significant effect was seen in affluent, rural areas., (Copyright 2002 Cancer Research UK)

Study Objective: To describe the advantages of using Poisson regression methods as an alternative to standardisation when computing expected numbers of disease occurrences adjusted for possible confounding factors. The problem of assessing the adequacy of model fit when the expectations are small is addressed by analytical calculations and by simulation. The method is illustrated with data from the national register of childhood tumours., Design: The tumour data are recorded in a national register., Setting: England, Scotland, and Wales., Subjects: The cases considered are all children registered with leukaemia or non-Hodgkin lymphoma under the age of 15 years between 1966-87., Main Results: The methods show a significant variation of leukaemia incidence in relation to the Register General's standard region and a negative association with socioeconomic deprivation, as measured by the Townsend index. After allowing for these variables, the incidence seems to be reasonably homogeneous throughout the population, in the sense that the residual deviance does not seem to be much larger than would be expected by chance., Conclusions: The methods described have major advantages over standardisation in controlling for confounding, both in terms of flexibility of factor selection and assessment and also in the ability to determine whether there is residual variability of incidence after allowing for these factors.

A recent study by Knox concludes that cases and "clusters" of two or more cases of childhood leukaemia and non-Hodgkin's lymphoma occur closer to many kinds of industrial installation than to supposedly comparable control locations. It is argued that these findings could be largely or entirely artefactual, the apparent differences arising out of the inappropriateness of the control data. Knox used randomly selected postcode units as controls, a procedure that leads to the comparison of individuals located in areas with typically quite different population densities from those for the cases. The resulting potential for bias is explored and the arguments are exemplified by analysing household data based on postcodes.

Objective: To examine the relation between the risk of childhood leukaemia and non-Hodgkin's lymphoma and proximity of residence to nuclear installations in England and Wales., Design: Observed and expected numbers of cases were calculated and analysed by standard methods based on ratios of observed to expected counts and by a new statistical test, the linear risk score test, based on ranks and designed to be sensitive to excess incidence in close proximity to a putative source of risk., Setting: Electoral wards within 25 km of 23 nuclear installations and six control sites that had been investigated for suitability for generating stations but never used., Subjects: Children below age 15 in England and Wales, 1966-87., Main Outcome Measure: Registration of any leukaemia or non-Hodgkin's lymphoma., Results: In none of the 25 km circles around the installations was the incidence ratio significantly greater than 1.0. The only significant results for the linear risk score test were for Sellafield (P = 0.00002) and Burghfield (P = 0.031). The circles for Aldermaston and Burghfield overlap; the incidence ratio was 1.10 in each. One of the control sites gave a significant linear risk score test result (P = 0.020). All the tests carried out were one sided with P values estimated by simulation., Conclusion: There is no evidence of a general increase of childhood leukaemia or non-Hodgkin's lymphoma around nuclear installations. Apart from Sellafield, the evidence for distance related risk is very weak.

The effects of a range of concentrations of halothane upon lower oesophageal contractility (LOC) and on defined clinical signs has been studied in patients undergoing surgery. Changes in clinical signs were assigned a numerical value by means of a scoring system. One hundred and eighty-one sets of measurements were made in 46 patients exposed to concentrations of halothane between 2.0 and 0.5 minimum alveolar concentration (MAC). The results were examined to identify relationships between (i) the clinical signs and alveolar halothane concentration, (ii) the clinical signs and LOC and (iii) the changes in LOC and alveolar concentration; significant correlations were found between these variables. Decreasing alveolar halothane concentration was associated with an increase in LOC and these increases in LOC were also associated with increases in the clinical score.

There is great public concern, often based on anecdotal reports, about risks from ionising radiation. Recent interest has been directed at an excess of leukaemia cases in the locality of civil nuclear installations at Sellafield and Sizewell, and epidemiologists have a duty to pursue such information vigorously. This paper sets out to show that the epidemiological methods most commonly used can be improved upon. When analysing geographical data it is necessary to consider location. The most obvious quantification of location is ranked distance, though other measures which may be more meaningful in relation to aetiology may be substituted. A test based on distance ranks, the "Poisson maximum test", depends on the maximum of observed relative risk in regions of increasing size, but with significance level adjusted for selection. Applying this test to data from Sellafield and Sizewell shows that the excess of leukaemia incidence observed at Seascale, near Sellafield, is not an artefact due to data selection by region, and that the excess probably results from a genuine, if as yet unidentified cause (there being little evidence of any other locational association once the Seascale cases have been removed). So far as Sizewell is concerned, geographical proximity to the nuclear power station does not seem particularly important.

This paper reviews data relating to obstetric radiography from the Oxford Survey of Childhood Cancers, i.e. for deaths in Britain from 1953 to 1967. Some 8513 cases were traced and used in the analyses, together with an equal number of matched controls. The relative risk estimate (1-47 overall) does not vary significantly between different tumour groups, for different ages at death, nor between sexes. Other epidemiological factors-sibship position, maternal age, social class, region of residence and maternal morbidity-are analysed and show varying degrees of association, but not sufficient to "explain" the observed risk in terms of a selection effect. The dependence of the risk on the number of films exposed is highly significant and adequately described by a linear relationship. The timing of and reason for the exposure are also examined. Analysis of the risk by year of birth shows a pattern of steadily declining risk for both solid and haematopoietic tumours; this may be partly attributable to lower radiation doses per film exposed but is also due to the smaller numbers of films used. A consequence may well be that the risk-always of small clinical significance-would become virtually undetectable in future investigations.

The possibility of an association between virus infections during pregnancy and subsequent malignant disease in the child has been investigated using retrospective data from the Oxford Survey of Childhood Cancers. Such an association appears to exist for influenza, chickenpox, and possibly rubella. For influenza and rubella the estimated risk is small; the data do not permit an estimate to be made directly in the case of chickenpox. It is suggested that there may be a specific association between maternal chickenpox and tumours of the nervous system.It is important to emphasize that, even if the relative risk associated with these viruses is fairly large, the number of cases of childhood cancer and leukaemia actually attributable to them is probably very small.