Atopic dysfunction and risk of central nervous system tumours in children

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Abstract

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, CI95%: 0.58–0.97), though this was not observed for eczema (OR 0.94, CI95%: 0.74–1.18). Individuals who had suffered both asthma and eczema showed the most significant reduction in risk (OR 0.48, CI95%: 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.

Introduction

Central nervous system (CNS) tumours comprise approximately 20% of all childhood cancers in Europe1, making them the second most common group of childhood malignancies after leukaemia. Pathology of childhood CNS tumours is distinct from those of adults2. Attempts to identify underlying environmental risk factors have largely been unsuccessful with only ionising radiation known to confer an increased risk3. Rare genetic disorders such as neurofibromatosis I, Turcot’s syndrome and Gorlin’s syndrome can also predispose children to CNS tumours, but have been observed in less than 5% of cases4, 5.

Atopy is allergic hypersensitivity stemming from the overproduction of IgE antibodies, typically associated with a Th2 response against common environmental allergens, resulting from an imbalance between the Th1 and the Th2 driven immune responses6. Atopy has a complex genetic component 7 and is also influenced by environmental exposures8.

Atopic individuals are at increased risk of allergic diseases such as asthma, eczema and allergic rhinitis (hay fever), any or all of which can be indicators of atopic dysfunction. The prevalence of asthma 9, eczema and allergic rhinitis10 has increased in developed countries in recent years, with the UK consistently found to have among the highest levels worldwide9, 10, 11. The reasons behind this relatively recent trend are not fully understood, though the hygiene hypothesis has some support12. This proposes that lower levels of microbial and viral exposure early in life are responsible for the increase in prevalence of allergic disease.

Possible links between atopy and cancer have been widely investigated 13. Consistent negative associations have been observed with adult brain tumours14, 15, 16, 17, 18, 19, 20. Decreased risk of neuroblastoma in children has also been associated with atopy, although results did not attain significance21. However, there is a lack of published studies addressing the issue of atopy and the risk of childhood CNS tumours, the present study seeks to address this by utilising data from the UK Childhood Cancer Study (UKCCS).

Section snippets

Patients and methods

The UKCCS is a population-based case–control study set up with the aim of identifying risk factors for childhood cancer. Full details are described elsewhere22. Briefly, UK children diagnosed with cancer before 15 years of age were eligible for the study, which recruited subjects from 1991 to 1994 in Scotland and 1992–1996 in England and Wales. Following histopathological review CNS tumours were categorised into subgroups according to ICD-O morphology codes22; details are in Table 1.

Two

Results

There were 683 CNS cases and 7598 controls available. The participation rate was 82% for cases and 64% for controls. Children under the age of 2 years at diagnosis or diagnosis of their matched case were excluded (n = 108 cases, 1306 controls). Demographic information on cases and controls is given in Table 1.

Of the remaining 575 cases, 90 (15.7%) completed the January 1992 questionnaire, as did 474 (7.5%) of the 6292 controls before the revised January 1993 version was introduced. Consequently,

Discussion

The results from our study find that the risk of developing a CNS tumour of any type is significantly reduced in children reported to have suffered from asthma or both asthma and eczema. The associations are strongly driven by findings for the PNET subgroup of tumours, despite the small numbers. To our knowledge, this is the first report of inverse associations between CNS tumours and allergies in children. Similar findings have been reported for adult onset brain tumours14, 15, 16, 17, 18, 19,

Conflict of interest statement

None declared.

Acknowledgements

UKCCS Management committee – K.K Cheng, Central region; N. Day, East Anglia region; R Cartwright, A Craft, North East region; J.M. Birch, O.B. Eden, North West region; P.A. McKinney, Scotland; J. Peto, South East region; V. Beral, E. Roman, South Midlands region; P. Elwood, South Wales region; F.E. Alexander, South West region; C.E.D. Chilvers, Trent region; R. Doll, Epidemiological Studies Unit, University of Oxford, Oxford; C.M. Taylor Immunogenetics Laboratory, University of Manchester,

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