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Background: Record-based studies have generally reported association of higher childhood leukaemia incidence with higher socioeconomic status (SES), but recent findings are less consistent., Methods: We examined records from the National Registry of Childhood Tumours for evidence of this association in England and Wales during 1976-2005. All eligible leukaemia registrations (N=11940) were grouped by year of diagnosis in decades centred on census years 1981, 1991 and 2001 (N=3748, 3922, 4270, respectively). Using data from the census appropriate to the decade, SES for each case was measured by the child-population-weighted quintile of the Carstairs deprivation index of the census ward containing the address at diagnosis., Results: In each decade, the age-standardised leukaemia rate in the poorest quintile was ∼90% of the rate in the most affluent. Using Poisson regression, the age-adjusted rate ratio per quintile decrease in SES was 0.96 (95% confidence interval 0.94-0.98; P<0.001 for trend) in 1976-1985, 0.97 (0.95-0.99; P=0.008) in 1986-1995 and 0.97 (0.95-0.99; P=0.009) in 1996-2005. Similar association was evident for lymphoid leukaemia, the major subgroup (N=9588 in total), but not for acute myeloid (N=1868) or other/unspecified leukaemia (N=484)., Conclusion: Reported childhood leukaemia incidence in England and Wales continues to be higher in relatively affluent communities. Possible explanations include under-diagnosis of leukaemia in children from poorer communities, and/or association of higher SES with hypothesised risk factors, such as population mixing and delayed exposure to infection.

Background: Completeness of ascertainment is a very important aspect of cancer registration. There is no recent published estimate for childhood cancer in Britain., Methods: We estimated completeness of ascertainment by the National Registry of Childhood Tumours for cancer diagnosed under age 15 years in residents of Britain during 2003-04. Stratified two-source capture-recapture was applied to notifications from general cancer registries (CRs) and specialist clinicians. Variation in notification patterns was assessed by logistic regression. Results were verified by cross-checking with Hospital Episode Statistics for leukaemia patients from England born in 1998 and diagnosed before 2005., Results: CRs notified 92-96% of registrations, and specialist clinicians 93%. Notification patterns varied slightly according to registry region, age at diagnosis, diagnostic group, socioeconomic status, and whether the patient had died. Irrespective of stratification by these factors, the overall completeness estimate was 99-100% (assuming independence of sources). Estimated completeness was at least 99% within all subgroups, except for one region (Thames 98-99%) and two small diagnostic groups (germ-cell and gonadal cancer 98-99%, melanoma and non-skin cancer 97-98%)., Interpretation: The independence assumption cannot be fully justified, as both sources used records from treatment centres. With this caveat, ascertainment of recently diagnosed childhood cancer in Britain appears to be virtually complete.

In this population-based study of acute lymphoblastic leukaemia (ALL) diagnosed among children aged under 15 years in England and Wales during 1986-1995, we analysed incidence at census ward level in relation to a range of variables from the 1991 census, which could be relevant to theories of infectious aetiology. 'Population-mixing' measures, used as surrogates for quantity and diversity of infections entering the community, were calculated from census data on the origins and destinations of migrants in the year before the census. Incidence at ages 1-4 years tended independently to be higher in rural wards, to increase with the diversity of origin wards from which in-migrants had moved during the year before the census, and to be lower in the most deprived areas as categorised by the Carstairs index. This last association was much weaker when urban/rural status and in-migrants' diversity were allowed for. There was no evidence of association with population mixing or deprivation for ALL diagnosed at ages 0 or 5-14 years. The apparent specificity to the young childhood age group suggests that these associations are particularly marked for precursor B-cell ALL, with the disease more likely to occur when delayed exposure to infection leads to increased immunological stress, as predicted by Greaves. The association with diversity of incomers, especially in rural areas, is also consistent with the higher incidence of leukaemia predicted by Kinlen, where population mixing results in below average herd immunity to an infectious agent.

The purpose of the study was to calculate population-based survival rates for osteosarcoma (OS) and Ewing's sarcoma (ES) in Great Britain during 1980-1994, determine proportions of patients treated at specialist centres or entered in national and international clinical trials, and investigate effects of these factors on survival. Data on a population-based series of 1349 patients with OS and 849 with ES were compiled from regional and national cancer registries, UK Children's Cancer Study Group, regional bone tumour registries and clinical trials. Follow-up was through population registers. Survival was analysed by actuarial analysis with log-rank tests and by Cox's proportional hazards analysis. Five-year survival rates during 1980-1984, 1985-1989 and 1990-1994 were 42% (95% CI: 37, 46), 54% (95% CI: 50, 59) and 53% (95% CI: 48, 57), respectively, for OS and 31% (95% CI: 26, 37), 46% (95% CI: 40, 51) and 51% (95% CI: 45, 57) for ES. Proportions of patients treated at a supraregional bone tumour centre or a paediatric oncology centre in the three quinquennia were 36, 56 and 67% for OS and 41, 60 and 69% for ES. In 1983-1992, 48% of OS patients were entered in a national trial; for ES, 27% were entered in 1980-1986 and 54% in 1987-1994. Survival was similar for trial and nontrial patients with OS. For ES, trial patients had consistently higher 5-year survival than nontrial patients: 1980-1986, 42 vs 30%; 1987-1992, 59 vs 42%; 1993-1994, 54 vs 43%. During 1985-1994, patients with OS or ES whose main treatment centre was a nonteaching hospital had lower survival rates. In multivariate analyses of patients diagnosed during 1985-1994 that also included age, sex, primary site, surgical treatment centre, the results relating to main treatment centre for both OS and ES retained significance but the survival advantage of trial entry for ES became nonsignificant. For both OS and ES diagnosed since 1985, patients whose main treatment centre was a nonspecialist hospital had a lower survival rate.

The incidence of testicular cancer has been increasing markedly in most industrialised countries. This rise is known to have affected young adults, but it is less clear whether it has affected other age groups, particularly children. We used data from the National Cancer Registry file at the Office of National Statistics (ONS) and the National Registry of Childhood Tumours to examine trends in testicular germ-cell malignancies overall in England and Wales from 1962 to 1990 and in children from 1962 to 1995. The incidence of testicular cancer at all ages rose by 3.4% (95% CI 3.3-3.6%) per annum from 1962 to 1990. A similar rise in the incidence of germ-cell malignancies occurred during the years for which histological information was available in the ONS files, 1971-1989 (3.4%; 3.1-3.6%), to which both seminomas and non-seminomas contributed equally. The incidence of non-seminomas in adults rose in men under age 55 years and declined in older men, whereas there were increases in the incidence of seminomas in both young and older men. Cohort analysis at young ages showed a marked rise in the risk of germ-cell malignancies up to the cohort born in 1955-1959 but no further rise for those born subsequently. The rise in the incidence of these tumours in young adults was paralleled by a similar trend, although less marked, in children aged under 15 years (1.3% per annum; 0.2-2.5%). The increase in risk for children in this very large data set alongside the rise in young adults is compatible with the hypothesis that childhood and adult testicular germ-cell malignancies may have some common risk factors, presumably pre-natal., (Copyright 1999 Wiley-Liss, Inc.)

We report a population-based study of patterns of care and survival for people with acute leukaemia diagnosed at age 15-29 years during 1984-94 in regions of England and Wales covered by specialist leukaemia registries. There were 879 patients: 417 with acute lymphoblastic leukaemia (ALL) and 462 with acute myeloid leukaemia (AML). For ALL, actuarial survival rates were 43% at 5 years after diagnosis and 37% at 10 years. Survival improved significantly between 1984-88 and 1989-94 for those aged 15-19 at diagnosis. Patients entered in national clinical trials and those not entered had similar survival rates. Survival rates were similar at teaching and non-teaching hospitals and at hospitals treating different numbers of study patients per year. For AML, survival rates were 42% at 5 years after diagnosis and 39% at 10 years. Survival improved significantly between 1984-88 and 1989-94. Patients entered in the Medical Research Council AML10 trial had a higher survival rate than those who were in the earlier AML9 trial. Survival did not vary with category of hospital. We conclude that survival has improved for adolescents and young adults with acute leukaemia but that there is at present no evidence that centralized treatment results in a survival benefit for patients in this age group.

Objective: To examine the effects of migration, diversity of migrant origins, commuting, and socioeconomic status on the incidence of acute lymphoblastic leukaemia in childhood., Design: Poisson regression analysis of incidence rates in relation to the variables of interest., Setting: The 403 county districts of England and Wales during 1979-85., Subjects: Children aged under 15 years., Results: There were significant trends in the incidence of lymphoblastic leukaemia at ages 0-4 and 5-9 years with the proportion of children in a district who had recently entered the district. While there was no consistent relation between the proportion of recent incomers in the total population of a district and its incidence rate, the combination of higher migration with greater diversity of origins or distance moved was associated with higher incidence in both age groups. Incidence increased significantly at age 0-4 with the level of employment in a district and at age 5-9 with the proportion of households with access to a car. No significant trends were found with commuting., Conclusions: The results for level of child migration and diversity of total migration provide evidence of an effect of population mixing on the incidence of childhood leukaemia which is not restricted to areas experiencing the most extreme levels of mixing.

Generalizations of the two-mutation carcinogenesis model of Moolgavkar, Venzon and Knudson (MVK) are fitted to England and Wales lymphocytic leukaemia incidence data covering the period 1971-1988. Both acute lymphocytic leukaemia (ALL) and chronic lymphocytic leukaemia (CLL) can be fitted by a model with two mutations. These two-mutation models are such that the first (but not the second) mutation rate and the susceptible stem cell population vary rapidly with age. CLL is also adequately fitted by a model with three mutations, and the mutation rates and the variation in the stem cell population numbers implied by the three-mutation model are more plausible than those of the two-mutation model. For CLL there are no significant differences between the sexes in either of the optimal models fitted, but this is not the case for ALL. Thus the original MVK model adequately describes population rates of lymphocytic leukaemia in England and Wales.

The National Registry of Childhood Tumours contains population-based data on childhood cancers diagnosed throughout Great Britain from 1962 onwards. This paper describes the methodology of the Registry, presents incidence rates for 1978-1987 and describes other uses of the data. Total age-standardised annual incidence was 118.3 per million. The most frequent diagnostic groups were leukaemias (age-standardised rate 39.8), brain and spinal tumours (27.0), lymphomas (11.1), sympathetic nervous system tumours (8.3), kidney tumours (7.7) and soft-tissue sarcomas (7.5). Incidence rates were similar to those reported from other Western industrialised countries. The data are also used for a wide range of epidemiological and other studies. These include analyses of geographical variations in incidence, trends in survival, health of long-term survivors and their offspring and the genetics of childhood cancer. Information is frequently provided for clinicians and research workers, and series of specific types of cancer are compiled for further study. The Registry depends for the completeness and accuracy of its data on a wide range of organisations and individuals, and it is essential that this cooperation continues if the Registry is to be maintained.

Objective: To determine whether population mixing produced by large, non-nuclear construction projects in rural areas is associated with an increase in childhood leukaemia and non-Hodgkin's lymphoma., Design: A study of the incidence of leukaemia and non-Hodgkin's lymphoma among children living near large construction projects in Britain since 1945, situated more than 20 km from a population centre, involving a workforce of more than 1000, and built over three or more calendar years. For periods before 1962 mortality was studied., Setting: Areas within 10 km of relevant sites, and the highland counties of Scotland with many hydroelectric schemes., Subjects: Children aged under 15., Results: A 37% excess of leukaemia and non-Hodgkin's lymphoma at 0-14 years of age was recorded during construction and the following calendar year. The excesses were greater at times when construction workers and operating staff overlapped (72%), particularly in areas of relatively high social class. For several sites the excesses were similar to or greater than that near the nuclear site of Sellafield (67%), which is distinctive in its large workforce with many construction workers. Seascale, near Sellafield, with a ninefold increase had an unusually high proportion of residents in social class I. The only study parish of comparable social class also showed a significant excess, with a confidence interval that included the Seascale excess., Conclusion: The findings support the infection hypothesis and reinforce the view that the excess of childhood leukaemia and non-Hodgkin's lymphoma near Sellafield has a similar explanation.

Objective: To reappraise the epidemiological findings reported by the Black Advisory Group concerning a possible excess of malignant disease, particularly of childhood acute lymphoid leukaemia and non-Hodgkin lymphomas, in the vicinity of the Sellafield nuclear installation, and to determine whether any excess of malignant disease had occurred among people aged 0-24 years in the area in the years after the Black report--that is, from 1984 to 1990., Design: Calculation of incidence of cancer using data from population based cancer registries and special surveys., Setting: England and Wales; county of Cumbria; county districts Allerdale and Copeland within Cumbria; Seascale ward within Copeland., Subjects: All residents under the age of 75 years in the above areas, but with particular reference to those aged 0-24 years., Main Outcome Measures: Numbers of cases and incidence particularly of lymphoid leukaemia and non-Hodgkin lymphomas in those aged 0-24 years, but including other cancers and age groups., Results: Previous reports of an increased incidence of cancer, especially of leukaemia, among those aged 0-24 years in Seascale during the period up to and including 1983 are confirmed. During 1984-90 there was an excess of total cancer among those aged 0-24 years. This was based on four cases including two cases of non-Hodgkin lymphoma but none of leukaemia. There was an increased, but nonsignificant, incidence of other cancers, based on two cases (one pinealoma and one Hodgkin's disease) occurring among those aged 15-24 years during 1984-90. This was not observed in the younger age group or in previous years. For the immediately surrounding area--that is, the county districts of Allerdale and Copeland excluding Seascale and in the remainder of Cumbria--there was no evidence of an increased incidence of cancer among those aged 0-24 years in either period., Conclusions: During 1963-83 and 1984-90 the incidence of malignant disease, particularly lymphoid leukaemia and non-Hodgkin lymphomas, in young people aged 0-24 in Seascale was higher than would be expected on the basis of either national rates or those for the surrounding areas. Although this increased risk is unlikely to be due to chance, the reasons for it are still unknown.

The increasing tendency for people to work outside their home community--one of the most striking of modern demographic changes--has relevance to a recent aetiological hypothesis about childhood leukaemia: that a community's immune response to an underlying infection can be disturbed by increases in new social contacts. This was tested in the only 28 former county boroughs in which accurate comparisons of workplace data from the 1971 and 1981 censuses are possible--because their boundaries were left unaltered by the major reorganisation in 1974. After ranking the districts according to extent of commuting increase, a significant trend in leukaemia incidence was found at ages 0-14 (P less than 0.05) and a suggestive one at ages 0-4 (P = 0.055). Among ten similar sized groups of county districts ranked by commuting increase, the only significant increases (P less than 0.001) of leukaemia in 1972-85 at ages 0-4 and 0-14 were in the highest tenth for commuting increase. These excesses persisted after excluding Reading, a major part of an area where an excess of leukaemia has been linked to the nearby nuclear establishments at Aldermaston and Burghfield. This whole area has experienced greater commuting increases than 90% of county districts in England and Wales. The findings are consistent with other evidence supporting the above hypothesis; they also suggest that contacts between adults may influence the incidence of leukaemia in children.

The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC) was established to investigate the role of possible aetiological factors in childhood cancer, with particular emphasis on environmental exposures to the foetus and family history of certain diseases including cancer. Incident cases occurring in three Health Service regions (the West Midlands, Yorkshire and North Western) were matched for age and sex with two sets of control children. A total of 555 cases and 1110 controls were entered into the study. The parents of each index child were interviewed with respect to events during the relevant pregnancy, occupation, smoking habits, and past medical history of themselves, the child's siblings and other relatives. Ninety-three per cent of case parents approached agreed to be interviewed, and approximately 90% of controls were ranked first or second on the control selection lists. After the interview information was verified by reference to antenatal and other medical records. Obstetric and general practitioner records were abstracted for approximately 90% of cases and controls. Information derived from the interview and that from medical records was coded separately. The data collected by each region have been pooled and case-control comparisons of potential aetiological factors will be carried out, using matched triplet analyses.