Children who receive a definite diagnosis of allergy in early life have a 20% reduced risk of developing acute lymphoblastic leukaemia (ALL), according to results from the first large-scale study to use contemporaneously collected primary care data to examine the association between childhood leukaemia and preceding allergy.

Several sources of evidence point to a role for abnormal immune responses as a critical determinant of childhood ALL, but most of the research in this area has focussed on infection as a potential cause rather than assessing the consequences of early allergies. The problem with investigating this issue is that parents' memories of childhood allergy are often used as the only source of information, but these reports may not give an accurate representation of actual diagnoses.

For this study, researchers from all over the UK , working as part of the UK Childhood Cancer Study, used primary care records from the time of allergy diagnosis to investigate potential mechanisms of altered ALL risk in addition to infection.

The cohort from which medical records were extracted is the largest and most comprehensive population-based case-control study of paediatric cancers, the United Kingdom Childhood Cancer Study (UKCCS), and includes children diagnosed with a cancer between 1991 and 1996, who were aged 14 or younger at the time the cancer was identified. Two controls per case were randomly selected from primary care population to complete the study group.

Using the subset of cases for which primary care records were systematically extracted, the investigators identified 839 leukaemia cases and 1337 matched controls for analysis. Information about lifetime occurrences of asthma, hayfever and eczema and prescriptions for corticosteroids, bronchodilators, and antihistamines were extracted from primary care records; recollections were also obtained from mothers using a questionnaire. Breastfeeding history and early birth order were also examined as potential confounder factors in cancer diagnosis since these features are considered to be proxies for reduced exposure to infectious agents in infancy, so might be associated with the development of atopic disease.

More than a third of cases and controls had at least one diagnosis of allergy in their medical records; of these, half had at least one definite diagnosis, assessed by a combination of number of episodes, prescriptions and parents' reports. The most common condition was eczema. A history of at least one probable allergy was associated with a 13-16% non-significant reduction in risk across all leukaemia subgroups, according to the authors. For ALL, the associations were stronger for definite allergy diagnoses than for probable casers, but this observation was not seen in for AML.

"In the UKCCS, we observed an around 20% reduction in risk for ALL and c-ALL following a definite diagnosis of allergy. The strongest association was observed with eczema and, to a lesser extent, hayfever, for which we observed statistically significant reductions in risk for total ALL and c-ALL of 30% and 40%, respectively," explain the authors.

They believe the most plausible biological explanation for these findings involve immune dysfunction. "Since both innate and adaptive immune responses are subject to genome-wide genetic variation, functional polymorphisms in key cytokine genes may result in distinct genetic susceptibility profiles that influence the nature of immune response to infectious agents," the researchers suggest.

"The way by which allergy might influence childhood leukaemia risk is not clear, although one possibility is that individuals with allergic conditions have immune systems with a greater capacity to detect and destroy aberrant cells…. Timing and chronicity of infectious exposure are likely to be critical in the relationship between ALL and allergy."

Allergy and risk of childhood leukaemia: Results from the UKCCS.
Hughes AM, Lightfoot T, Simpson J, Ansell P, McKinney PA , Kinsey SE, Mitchell CD, Eden TOB, Greaves M, Roman E on behalf of the United Kingdom Childhood Cancer Study Investigators.
International Journal of Cancer 2007; 121: 819-824

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