© The Author 2006. Published by Oxford University Press.
CORRESPONDENCE |
Re: Childhood Leukemia Incidence in Britain, 1974–2000: Time Trends and Possible Relation to Influenza Epidemics
Affiliations of authors: School of Clinical Medical Sciences (Child Health) and Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK (RJQM); Academic Unit of Paediatric and Adolescent Oncology, Christie Hospital NHS Trust and Central Manchester and Manchester Children's University Hospitals Trust, Manchester, UK (TOBE)
Correspondence to: Richard J. Q. McNally, PhD, Sir James Spence Institute, Newcastle University, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK (e-mail: richard.mcnally{at}ncl.ac.uk).
Kroll et al. (1) recently reported incidence time trends for childhood leukemia in Britain during 1974–2000 and suggested that small peaks in incidence may be associated with influenza epidemics. The authors observed an overall increase in childhood leukemia during this period that they attributed to precursor B-cell subtype of acute lymphoblastic leukemia (ALL). This finding is largely confirmatory of a previous, albeit smaller, study from Northwest England (2).
A number of previous epidemiologic studies have suggested that infectious disease may be involved in the etiology of childhood leukemia, and other studies have found that, as would be expected from such an etiology, cases of childhood leukemia display a propensity to cluster in space and time (3,4). Such an unusual pattern suggests that the putative infections occur in "mini-epidemics." By contrast, ubiquitous or endemic infections would not be predicted to lead to such space–time clustering. Our studies from Northwest England found that space–time clustering was limited to leukemia of precursor B-cell subtype (5). This observation provides additional evidence that epidemic infections may be involved with this subtype specifically. Finally, cyclical, epidemic-like patterns in the magnitude of the space–time clustering for childhood ALL have been observed (6), which suggests the involvement of one or more common infections in etiology.
There are a number of apparent limitations to the study by Kroll et al. (1). One is that it is not clear why the authors focused on influenza in particular. Several of other infectious agents, including measles, chicken pox, and adenovirus, are equally plausible candidates for an association with leukemia. The authors' suggestion that incidence peaks are linked to influenza appears to be based entirely on the observation that two small peaks in incidence of ALL occurred in the 2 years immediately following influenza epidemics. Although the authors note that the coincidence of two small peaks in ALL with influenza may be attributable to chance, they made no formal attempt to assess the statistical significance of this observation. Moreover, the proportion of extra ALL cases that occurred in the peak years that immediately followed the influenza epidemics is far less than the proportion of extra influenza cases. Thus, if influenza is involved in the etiology of childhood ALL, it must be involved for only a limited number of individuals. A large case–control study from the United Kingdom has suggested that infections may be involved in cases of ALL in patients who have a particular pattern of immune response genes (7). A more plausible hypothesis than the one of Kroll et al. is that it is the individual's response to infection rather than any specific infection that precipitates leukemia, but certain infections are more likely to stimulate a cytokine-driven proliferation. Finally, Kroll et al. analyzed data based on the time of diagnosis. However, an infection occurring in utero or around the time of birth would be predicted to generate an epidemic pattern based on time of birth, rather than time of diagnosis.
More research is needed to enhance understanding of the role that infections, including influenza, may play in the etiology of childhood ALL. Further studies on immune response genes as well as linkage to infectious disease patterns are required. Ultimately, such studies should lead to better understanding of leukemia etiology.
REFERENCES
(1) Kroll ME, Draper GJ, Stiller CA, Murphy MFG. Childhood leukemia incidence in Britain, 1974–2000: time trends and possible relation to influenza epidemics. J Natl Cancer Inst 2006;98:417–20.
(2) McNally RJQ, Birch JM, Taylor GM, Eden OB. Temporal increase in the incidence of childhood peak precursor B-cell acute lymphoblastic leukaemia seen in North West England. Lancet 2000;356:485–6.[CrossRef][ISI][Medline]
(3) McNally RJQ, Eden TOB. An infectious aetiology for childhood acute leukaemia: a review of the evidence. Br J Haematol 2004;127:243–63.[CrossRef][ISI][Medline]
(4) McNally RJQ, Alexander FE, Bithell JF. Space-time clustering of childhood cancer in Great Britain: a national study, 1969–1993. Int j Cancer 2006;118:2840–6.[CrossRef][ISI][Medline]
(5) McNally RJQ, Alexander FE, Birch JM. Space-time clustering analyses of childhood acute lymphoblastic leukaemia by immunophenotype. Br J Cancer 2002;87:513–5.[CrossRef][ISI][Medline]
(6) McNally RJQ, Birch JM, Taylor GM, Eden OB. Temporal trends in childhood leukaemia in North West England: 1954–1997. Eur J Cancer 1999;35:S277.
(7) Taylor GM, Dearden S, Ravetto P, Ayres M, Watson P, Hussain A, et al, UKCCS Investigators. United Kingdom Childhood Cancer Study. Genetic susceptibility to childhood common acute lymphoblastic leukaemia is associated with polymorphic peptide-binding pocket profiles in HLA-DPB1*0201. Hum Mol Genet 2002;11:1585–97.
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J Natl Cancer Inst 2006 98: 1746-1747.
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