UK Childhood Cancer Study Research Articles

Paediatric acute lymphoblastic leukaemia and caesarean section: A report from the United Kingdom Childhood Cancer Study (UKCCS).

BackgroundReports have suggested that children born by caesarean initiated before labour onset may be at increased risk of developing acute lymphoblastic leukaemia (ALL). However, with most data being derived from case‐control study interviews, information on the underpinning reasons for caesarean section is sparse, and evidence is conflicting.ObjectivesUse clinical records compiled at the time of delivery to investigate the association between childhood ALL and caesarean delivery; examining timing in relation to labour onset, and reasons for the procedure.MethodsData are from the UK Childhood Cancer Study, a population‐based case‐control study conducted in the 1990s, when caesarean section rates were relatively low, in England, Scotland, and Wales. Children with ALL were individually matched to two controls on sex, date of birth, and region of residence. Information on mode of delivery and complications was abstracted from obstetric records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression models adjusted for matching variables and relevant covariates.ResultsAround 75% of the 1034 cases and 1914 controls were born through unassisted vaginal delivery. Caesarean delivery was as frequent in cases and controls (OR 1.07, 95% CI 0.84, 1.36). No association was observed between ALL and caesarean delivery either during or before labour, with adjusted ORs of 1.08 (95% CI 0.78, 1.48) and 1.09 (95% CI 0.78, 1.53), respectively. For B‐cell ALL, the ORs were 1.14 (95% CI 0.81, 1.59) for caesarean during labour and 1.21 (95% CI 0.85, 1.72) for prelabour. The underpinning reasons for caesarean delivery differed between cases and controls; with preeclampsia, although very rare, being more common amongst cases born by caesarean (OR 8.91, 95% CI 1.48, 53.42).ConclusionsOur obstetric record‐based study found no significant evidence that caesarean delivery increased the risk of childhood ALL, either overall or when carried out before labour.

Levels of naturally occurring gamma radiation measured in British homes and their prediction in particular residences.

Gamma radiation from natural sources (including directly ionising cosmic rays) is an important component of background radiation. In the present paper, indoor measurements of naturally occurring gamma rays that were undertaken as part of the UK Childhood Cancer Study are summarised, and it is shown that these are broadly compatible with an earlier UK National Survey. The distribution of indoor gamma-ray dose rates in Great Britain is approximately normal with mean 96 nGy/h and standard deviation 23 nGy/h. Directly ionising cosmic rays contribute about one-third of the total. The expanded dataset allows a more detailed description than previously of indoor gamma-ray exposures and in particular their geographical variation. Various strategies for predicting indoor natural background gamma-ray dose rates were explored. In the first of these, a geostatistical model was fitted, which assumes an underlying geologically determined spatial variation, superimposed on which is a Gaussian stochastic process with Matérn correlation structure that models the observed tendency of dose rates in neighbouring houses to correlate. In the second approach, a number of dose-rate interpolation measures were first derived, based on averages over geologically or administratively defined areas or using distance-weighted averages of measurements at nearest-neighbour points. Linear regression was then used to derive an optimal linear combination of these interpolation measures. The predictive performances of the two models were compared via cross-validation, using a randomly selected 70 % of the data to fit the models and the remaining 30 % to test them. The mean square error (MSE) of the linear-regression model was lower than that of the Gaussian-Matérn model (MSE 378 and 411, respectively). The predictive performance of the two candidate models was also evaluated via simulation; the OLS model performs significantly better than the Gaussian-Matérn model.

The UK Childhood Cancer Study: maternal occupational exposures and childhood leukaemia and lymphoma

Risks of childhood leukaemia and lymphoma were investigated for specific work-related exposures of mothers in the UK Childhood Cancer Study. Interviews with parents of 1881 leukaemia and lymphoma cases (0-14 years) and 3742 controls collected job histories recording exposure to eight specific agents. Exposure was (1) self-reported and (2) reviewed, based mainly on exposure probability and exposure level. Completeness, consistency and sufficiency evaluated data quality. Of all job exposures which were self-reported as exposed, 33% cases and 34% controls remained classified as exposed after review, with the remainder designated as partially exposed or unexposed. No review of underreporting of exposure was made. Data quality was 'good' for 26% of cases and 24% of controls. For self-reported exposure, significant risks of acute lymphoblastic leukaemia (ALL) were observed for solvents and petrol in all time windows. For reviewed exposure, solvents remained significant for ALL during pregnancy and postnatally. Restricting analyses to good-quality information removed all significant results. Refinement of exposure assessment revealed misclassification of self-reported exposures and data quality influenced risk assessment. Maternal exposure to solvents should further be investigated. These findings must invoke caution in the interpretation of risks reliant on self-reported occupational data.

Infectious exposure in the first year of life and risk of central nervous system tumors in children: analysis of day care, social contact, and overcrowding

Little is known regarding the aetiology of central nervous system tumors in children. Recent studies have speculated on a potential infectious aetiology, but no clear associations have been found. This article uses parent reported questionnaire data from the UK Childhood Cancer Study (UKCCS), a population-based case-control study, to examine the relationship between the infectious exposure in the first year of life and the likelihood of developing a CNS tumor. The variables representing infectious exposure were social contact (including social contact with other infants and attendance at informal and formal day care), sharing a bedroom with another child, birth order, and exposure to a school-age child within the home. Children reported to have had no social contact with other infants in the first year of life displayed an increased risk of developing a CNS tumor when compared to those who had (OR 1.37, 95% CI 1.08-1.75). This effect was most prominent in the primitive neuroectodermal tumor/medulloblastoma subgroup (OR 1.78, 95% CI 1.12-2.83). Those who had attended informal (OR 0.86, 95% CI 0.68-1.09) or formal day care (OR 0.93, 95% CI 0.68-1.26) showed slightly non-statistically significant reduced risks when compared to those reporting social contact only. No association with any of the other variables was observed. Overall, the inconsistent findings by variable and tumor subtype suggest that an early exposure to infections is not strongly implicated in the aetiology of CNS tumors. However, the effect for social contact outside the home, particularly for PNET/medulloblastomas warrants further investigation.

Atopic dysfunction and risk of central nervous system tumours in children

Risk factors for central nervous system (CNS) tumours in children remain largely unknown. Evidence of an inverse relationship between atopy and tumour development exists in adults but little is known about childhood tumours. This study aims to examine the risk of childhood CNS tumours given a history of eczema and asthma. Cases of children diagnosed with CNS tumours ( n = 575) and controls ( n = 6292) from the UK Childhood Cancer Study (UKCCS) were analysed using conditional logistic regression comparing reported histories of allergic disease. Asthma was statistically significantly and negatively associated with all CNS tumours (odds ratios, OR 0.75, confidence of interval, CI 95%: 0.58–0.97), though this was not observed for eczema (OR 0.94, CI 95%: 0.74–1.18). Individuals who had suffered both asthma and eczema showed the most significant reduction in risk (OR 0.48, CI 95%: 0.28–0.81). Analysis by tumour subtype showed the strongest effect for the medulloblastoma/PNET group. These results may have a biological explanation with raised immunosurveillance in atopic individuals protecting against the development of brain tumours. Alternative explanations might include bias, reverse causality or confounding.

Breastfeeding and risk of childhood CNS tumours.

We investigated infant feeding habits in relation to risk of childhood central nervous system tumours among 633 cases in the UK Childhood Cancer Study (UKCCS). No significant effect of breastfeeding was detected overall (odds ratio 1.01, confidence interval: 0.85–1.21) nor in any morphological subgroup. Similarly, no effect for the duration of breastfeeding or any other feeding practices was observed.

Investigation of the sources of residential power frequency magnetic field exposure in theUK Childhood Cancer Study

There is an unexplained association between exposure to the magnetic fields arising fromthe supply and use of electricity, and increase in risk of childhood leukaemia. The UKChildhood Cancer Study (UKCCS) provides a large and unique source of information onresidential magnetic field exposure in the UK. The purpose of this supplementary studywas to investigate a sample of UKCCS homes in order to identify the particular sourcesthat contribute to elevated time-averaged exposure. In all, 196 homes have beeninvestigated, 102 with exposures estimated on the basis of the original study to be above0.2 µT, and 21higher than 0.4 µT, a threshold above which a raised risk has been observed. First, surveys werecarried out outside the property boundaries of all 196 study homes, and then,where informed consent had been obtained, assessments were conducted inside theproperties of 19 homes. The study found that low-voltage (LV) sources associatedwith the final electricity supply accounted together for 77% of exposures above0.2 µT, and 57% ofthose above 0.4 µT. Most of these exposures were linked to net currents in circuits inside and/or aroundthe home. High-voltage (HV) sources, including the HV overhead power linesthat are the focus of public concern, accounted for 23% of the exposures above0.2 µT, and 43% ofthose above 0.4 µT. Public health interest has focused on the consideration of precautionary measures thatwould reduce exposure to power frequency magnetic fields. Our study provides a basisfor considering the options for exposure mitigation in the UK. For instance, inelevated-exposure homes where net currents are higher than usual, if it is possible to reducethe net currents, then the exposure could be reduced for a sizeable proportion of thesehomes. Further investigations would be necessary to determine whether this is feasible.

Response to Kheifets et al. on “Comment concerning ‘childhood leukemia and residential magnetic fields: are pooled analyses more valid than the original studies?’”

BioelectromagneticsVolume 27, Issue 8 p. 675-676 ResponseFree Access Response to Kheifets et al. on “Comment concerning ‘childhood leukemia and residential magnetic fields: are pooled analyses more valid than the original studies?’” J. Mark Elwood, Corresponding Author J. Mark Elwood mark.elwood@cancervic.org.au Melbourne, AustraliaEpidemiologist, 1 Rathdowne St., Carlton 3053, Victoria, Australia.Search for more papers by this author J. Mark Elwood, Corresponding Author J. Mark Elwood mark.elwood@cancervic.org.au Melbourne, AustraliaEpidemiologist, 1 Rathdowne St., Carlton 3053, Victoria, Australia.Search for more papers by this author First published: 17 August 2006 https://doi.org/10.1002/bem.20256AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. REFERENCES Ahlbom A, Day N, Feychting M, Roman E, Skinner J, Dockerty J, Linet M, McBride M, Michaelis J, Olsen J, et al. 2000. A pooled analysis of magnetic fields and childhood leukemia. Br J Cancer 83: 692– 698. M Egger, G Davey Smith, DG Altman, editors. 2001. Systemic reviews in health care: Meta-analysis in context. London: BMJ Publishing Group. Elwood JM. 2006. Childhood leukemia and residential magnetic fields: Are pooled analyses more valid than the original studies? Bioelectromagnetics 27: 112– 118. Greenland S, Sheppard AR, Kaune WT, Poole C, Kelsh MA. 2000. A pooled analysis of magnetic fields, wire codes, and childhood leukemia. Epidemiology 11: 624– 634. Kheifets L, Mezei G, Greenland S. 2006. Comment concerning “Childhood leukemia and residential magnetic fields: Are pooled analyses more valid than the original studies?” Bioelectromagnetics 27: 674– 675. Linet MS, et al. 1997. Residential exposure to magnetic fields and acute lymphoblastic leukemia in children. N Engl J Med 337: 1– 7. McBride ML, et al. 1999. Power-frequency electric and magnetic fields and risk of childhood leukemia in Canada. Am J Epidemiol 149: 831– 842. Petitti DB. 2000. Meta-analysis, decision analysis, and cost-effectiveness analysis. Methods for quantitative synthesis in medicine. New York: Oxford University Press. The Cochrane Collaboration. 2005. Glossary of terms in the cochrane collaboration (updated May 2005). www.cochrane.org. UK Childhood Cancer Study Investigators. 1999. Exposure to power-frequency magnetic fields and the risk of childhood cancer. Lancet 354: 1925– 1931. Volume27, Issue8December 2006Pages 675-676 ReferencesRelatedInformation

Childhood Cancer and Social Contact: the Role of Paternal Occupation (United Kingdom)*

To investigate the relationship between childhood cancer (particularly leukaemia) and paternal occupational social contact (a proxy for potential exposure to infections) using the UK Childhood Cancer Study. Using a national population-based case-control study, self-reported occupational data from fathers of 3596 children diagnosed with cancer between 1991 and 1996 under 15 years of age (cases) and fathers of 7011 children without cancer (controls) were analysed. Associations were assessed using odds ratios (OR) calculated by time of exposure (birth, diagnosis), diagnostic group (all cancers, leukaemia, acute lymphoblastic leukaemia (ALL), central nervous system tumours, other cancers), level of occupational social contact (high, medium, low), urban-rural status at diagnosis and occupational title. From 371 occupations, 75 (20%) were classified as having high levels of occupational social contact, 31 (8%) as medium and the remaining 265 (71%) as low. No associations were apparent for fathers' occupational social contact overall, for any time period or diagnostic group. OR for leukaemia and high levels of paternal occupational social contact at birth and diagnosis being 1.02 (95% confidence interval (CI) = 0.88-1.18) and 0.91 (95% CI = 0.79-1.06), respectively. Analyses by urban-rural status at diagnosis and by occupational title revealed no notable associations. The analyses of paternal occupational histories do not support the suggested association between high levels of paternal occupational social contact and an increased risk of childhood leukaemia. However, the role of participation bias should not be discounted.

Power to confuse

Ever since Nancy Wertheimer of the University of Colorado reported her 1979 findings of an excess of cancer in children living near overhead power lines, seldom has a year passed...

Breastfeeding and childhood cancer.

The relationship between childhood cancer and having been breastfed in infancy was investigated in the UK Childhood Cancer Study (UKCCS), a national, population-based case-control study. Analyses included 3500 children with cancer (cases) of whom 1637 were diagnosed with leukaemia, 114 with Hodgkin's disease, 228 with non-Hodgkin's lymphoma and 1521 with other cancer and 6964 controls. 62% cases and 64% controls were reported to have ever been breastfed. There was weak evidence, of borderline statistical significance, that having been breastfed was associated with a small reduction in the odds ratios for leukaemia (odds ratio = 0.89, 95% Cl 0.80–1.00, P = 0.06), and for all cancers combined (odds ratio = 0.92, 95% Cl 0.84–1.00, P = 0.05). Combining data from the UKCCS with results from other published studies showed a small reduction in the odds ratios for leukaemia, Hodgkin's disease, non-haematological cancers, and all childhood cancers combined, associated with ever having been breastfed. It is unclear whether the apparent small reduction in the odds ratio for these various types of childhood cancer is a generalized effect of breastfeeding or whether it reflects some systematic bias in the majority of studies that have investigated the question. © 2001 Cancer Research Campaign http://www.bjcancer.com

Attitudes and impressions of participants in a study of the causes of childhood cancer.

Researchers and ethics committees are increasingly concerned about the perceived emotional impact on individuals following participation in epidemiologic studies. This attitudinal survey was designed to investigate this issue among 751 of the parents who had already given an interview in the UK Childhood Cancer Study (UKCCS), one of the largest case-control studies ever undertaken to investigate the aetiology of cancer in children. Information was collected by postal questionnaire on their reasons for agreeing to take part in the UKCCS, on whether questions had caused distress or difficulty and what their feelings were immediately after the interview and at the time of this survey. Parents were asked if they felt they had benefited in any way by taking part and control parents were asked if they would have taken part without prior consent of their doctor. 90% of both cases and controls felt glad to have taken part immediately after the interview and few reported any anxiety at having done so; 95% of both cases and controls felt satisfied that they had made a worthwhile contribution. Although 18% of cases felt tense and 14% felt unhappy after the interview, over 90% of them felt glad that they had taken part a few weeks later. Of particular interest is that 38% of cases and 24% of controls said they had positively benefited from taking part in the UKCCS and 96% of control mothers did not mind their family doctor giving permission for them to be contacted. © 2001 Cancer Research Campaign http://www.bjcancer.com

Exposure to power-frequency magnetic fields and the risk of childhood cancer

<h2>Summary</h2><h3>Background</h3> Previous studies have suggested an association between exposure to power-frequency electromagnetic fields (EMF) and the development of childhood malignant disease, especially leukaemia and tumours of the central nervous system. We investigated the relation between all childhood cancer and exposure to power-frequency magnetic fields. <h3>Methods</h3> The UK Childhood Cancer Study was a population case-control study covering the whole of England, Wales, and Scotland. All children with a confirmed malignant disorder were potentially eligible. For each case, we matched two controls on date of birth and sex, randomly chosen from the list of the Family Health Services Authority in England and Wales or Health Board in Scotland. In the main study, 3838 cases and 7629 controls were interviewed. The EMF part of the study included only one control per case, and household EMF measurements and school measurements where relevant were taken on 2226 matched pairs. These measurements, adjusted for historical line load and appliance fields, were used to estimate average exposure in the year before the date of diagnosis, or an equivalent date for controls. Analyses were by conditional logistic regression, incorporating a census-derived deprivation index used as a measure of socioeconomic status. <h3>Findings</h3> For children with mean exposures of more than 0·2 μT compared with children with mean exposures of less than 0·1 μT, the adjusted odds ratios were 0·92 (95% CI 0·47–1·79) for acute lymphoblastic leukaemia, 0·90 (0·49–1·63) for all leukaemia, 0·46 (0·11–1·86) for central-nervous-system tumours, 0·97 (0·46–2·05) for other malignant disease, and 0·87 (0·56–1·35) for all malignant disease combined. Higher exposures (>0·4 μT) were recorded for only 17 (<0·4%) individuals (eight cases, nine controls). <h3>Interpretation</h3> This study provides no evidence that exposure to magnetic fields associated with the electricity supply in the UK increases risks for childhood leukaemia, cancers of the central nervous system, or any other childhood cancer.