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Spatial clustering and space–time clusters of leukemia among children in Germany, 1987–2007

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Abstract

Leukemia is the most frequent malignancy in children under the age of 15 years. The question of whether childhood leukemia has a tendency for clustering or forms clusters has been studied for several decades. The environmental risk factor discussed most often is infection, which might result in spatial clustering and space–time clusters. The German Childhood Cancer Registry provided data on 11,946 children with leukemia diagnosed during 1987–2007, as classified in the International Classification for Childhood Cancer (third edition), aggregated by municipality. We used the Potthoff–Whittinghill model to test for a general trend for clustering and the spatial scan statistic to search for localized clusters. No evidence of global clustering was found, neither for the whole study population nor in sub-groups by age, period or population density, or for different types of leukemia. A similar result was found for localized clusters. The analysis shows no evidence of a tendency to clustering, however, aggregation of data at the municipality level might have diluted small localized clusters. The results of this study do not provide support for the hypothesis of an infectious or a spatial environmental etiology of childhood leukemia.

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Abbreviations

ALL:

Acute lymphoblastic leukemia

AML:

Acute myeloblastic leukemia

COMARE:

Committee on Medical Aspects of Radiation in the Environment

ICCC:

International Classification of Childhood Cancer

CI:

Confidence interval

References

  1. Greaves M. Science, medicine, and the future: childhood leukaemia. BMJ. 2002;324(7332):283–7.

    Article  PubMed  Google Scholar 

  2. Kellett CE. Acute myeloid leukaemia in one of identical twins. Arch Dis Child. 1937;12(70):239–52.

    Article  Google Scholar 

  3. Besag J, Newell J. The detection of clusters in rare diseases. J R Stat Soc Ser A. 1991;154(1):143–55.

    Article  Google Scholar 

  4. Ward G. The infective theory of acute leukaemia. Br J Child Dis. 1917;24:10–20.

    Google Scholar 

  5. Kinlen LJ. Evidence for an infective cause of childhood leukaemia: comparison of a Scottish new town with nuclear reprocessing sites in Britain. Lancet. 1988;2(8624):1323–7.

    Article  CAS  PubMed  Google Scholar 

  6. Knudson AG Jr. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA. 1971;68(4):820–3.

    Article  PubMed  Google Scholar 

  7. Smith M. Considerations on a possible viral etiology for B-precursor acute lymphoblastic leukemia of childhood. J Immunother. 1997;20(2):89–100.

    Article  CAS  PubMed  Google Scholar 

  8. Muir KR, Parkes SE, Mann JR, Stevens MC, Cameron AH, Raafat F, Darbyshire PJ, Ingram DR, Davis A, Gascoigne D. Clustering’—real or apparent? Probability maps of childhood cancer in the West Midlands Health Authority Region. Int J Epidemiol. 1990;19(4):853–9.

    Article  CAS  PubMed  Google Scholar 

  9. Hjalmars U, Kulldorff M, Gustafsson G, Nagarwalla N. Childhood leukaemia in Sweden: using GIS and a spatial scan statistic for cluster detection. Stat Med. 1996;15(7–9):707–15.

    Article  CAS  PubMed  Google Scholar 

  10. Mosavi-Jarrahi A, Moini M, Mohagheghi MA, Alebouyeh M, Yazdizadeh B, Shahabian A, Nahvijo A, Alizadeh R. Clustering of childhood cancer in the inner city of Tehran metropolitan area: a GIS-based analysis. Int J Hyg Environ Health. 2007;210(2):113–9.

    Article  PubMed  Google Scholar 

  11. Westermeier T, Michaelis J. Applicability of the Poisson distribution to model the data of the German Children’s Cancer Registry. Radiat Environ Biophys. 1995;34(1):7–11.

    Article  CAS  PubMed  Google Scholar 

  12. Knox EG, Gilman EA. Spatial clustering of childhood cancers in Great Britain. J Epidemiol Community Health. 1996;50(3):313–9.

    Article  CAS  PubMed  Google Scholar 

  13. Petridou E, Alexander FE, Trichopoulos D, Revinthi K, Dessypris N, Wray N, Haidas S, Koliouskas D, Kosmidis H, Piperopoulou F, Tzortzatou F. Aggregation of childhood leukemia in geographic areas of Greece. Cancer Causes Control. 1997;8(2):239–45.

    Article  CAS  PubMed  Google Scholar 

  14. Alexander FE, Chan LC, Lam TH, Yuen P, Leung NK, Ha SY, Yuen HL, Li CK, Li CK, Lau YL, Greaves MF. Clustering of childhood leukaemia in Hong Kong: association with the childhood peak and common acute lymphoblastic leukaemia and with population mixing. Br J Cancer. 1997;75(3):457–63.

    CAS  PubMed  Google Scholar 

  15. Alexander FE, Boyle P, Carli PM, Coebergh JW, Draper GJ, Ekbom A, Levi F, McKinney PA, McWhirter W, Michaelis J, Peris-Bonet R, Petridou E, Pompe-Kirn V, Plìsko I, Pukkala E, Rahu M, Storm H, Terracini B, Vatten L, Wray N. Spatial clustering of childhood leukaemia: summary results from the EUROCLUS project. Br J Cancer. 1998;77(5):818–24.

    CAS  PubMed  Google Scholar 

  16. Dockerty JD, Sharples KJ, Borman B. An assessment of spatial clustering of leukaemias and lymphomas among young people in New Zealand. J Epidemiol Community Health. 1999;53(3):154–8.

    Article  CAS  PubMed  Google Scholar 

  17. McNally RJQ, Alexander FE, Vincent TJ, Murphy MF. Spatial clustering of childhood cancer in Great Britain during the period 1969–1993. Int J Cancer. 2009;124(4):932–6.

    Article  CAS  PubMed  Google Scholar 

  18. Gilman EA, Knox EG. Childhood cancers: space–time distribution in Britain. J Epidemiol Community Health. 1995;49(2):158–63.

    Article  CAS  PubMed  Google Scholar 

  19. Gustafsson B, Carstensen J. Space–time clustering of childhood lymphatic leukaemias and non-Hodgkin’s lymphomas in Sweden. Eur J Epidemiol. 2000;16(12):1111–6.

    Article  CAS  PubMed  Google Scholar 

  20. Birch JM, Alexander FE, Blair V, Eden OB, Taylor GM, McNally RJQ. Space–time clustering patterns in childhood leukaemia support a role for infection. Br J Cancer. 2000;82(9):1571–6.

    Article  CAS  PubMed  Google Scholar 

  21. McNally RJQ, Alexander FE, Birch JM. Space–time clustering analyses of childhood acute lymphoblastic leukaemia by immunophenotype. Br J Cancer. 2002;87(5):513–5.

    Article  CAS  PubMed  Google Scholar 

  22. Bellec S, Hémon D, Rudant J, Goubin A, Clavel J. Spatial and space–time clustering of childhood acute leukaemia in France from 1990 to 2000: a nationwide study. Br J Cancer. 2006;94(5):763–70.

    CAS  PubMed  Google Scholar 

  23. Committee on Medical Aspects of Radiation in the Environment (COMARE). Eleventh report. The distribution of childhood leukaemia and other childhood cancer in Great Britain 1969–1993. Health Protection Agency; 2006.

  24. McNally RJQ, Eden TO. An infectious aetiology for childhood acute leukaemia: a review of the evidence. Br J Haematol. 2004;127(3):243–63.

    Article  PubMed  Google Scholar 

  25. Raaschou-Nielsen O. Indoor radon and childhood leukaemia. Radiat Prot Dosimetry. 2008;132(2):175–81.

    Article  CAS  PubMed  Google Scholar 

  26. Whitworth KW, Symanski E, Coker AL. Childhood lymphohematopoietic cancer incidence and hazardous air pollutants in southeast Texas, 1995–2004. Environ Health Perspect. 2008;116(11):1576–80.

    Article  PubMed  Google Scholar 

  27. Rudant J, Menegaux F, Leverger G, Baruchel A, Nelken B, Bertrand Y, Patte C, Pacquement H, Vérité C, Robert A, Michel G, Margueritte G, Gandemer V, Hémon D, Clavel J. Household exposure to pesticides and risk of childhood hematopoietic malignancies: the ESCALE study (SFCE). Environ Health Perspect. 2007;115(12):1787–93.

    Article  PubMed  Google Scholar 

  28. Kaatsch P, Spix C. German Childhood Cancer Registry. Annual report 2006/2007. University Mainz; 2007.

  29. Steliarova-Foucher E, Kaatsch P, Lacour B, Pompe-Kirn V, Eser S, Miranda A, Danzon A, Ratiu A, Parkin DM. Quality, comparability and methods of analysis of data on childhood cancer in Europe (1978–1997): report from the ACCIS project. Eur J Cancer. 2006;42(13):1915–51.

    Article  CAS  PubMed  Google Scholar 

  30. Steliarova-Foucher E, Stiller C, Lacour B, Kaatsch P. International Classification of Childhood Cancer, third edition. Cancer. 2005;103(7):1457–67.

    Article  PubMed  Google Scholar 

  31. Fisher RA. The significance of deviations from expectation in a Poisson series. Biometrics. 1964;20(2):265–72.

    Article  Google Scholar 

  32. Potthoff RF, Whittinghill M. Testing for homogeneity. I. The binomial and multinomial distribution. Biometrika. 1966;53(1):167–82.

    CAS  PubMed  Google Scholar 

  33. Potthoff RF, Whittinghill M. Testing for homogeneity. II. The Poisson distribution. Biometrika. 1966;53(1):183–90.

    CAS  PubMed  Google Scholar 

  34. Muirhead CR. Methods for detecting disease clustering, with consideration of childhood leukaemia. Stat Meth Med Res. 2006;15(4):363–83.

    Article  Google Scholar 

  35. R Development Core Team. R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna. ISBN 3900051070. http://www.R-project.org (2009).

  36. Kulldorff M. A spatial scan statistic. Commun Statist Theory Meth. 1997;26(6):1481–96.

    Article  Google Scholar 

  37. Kulldorff M. SatScanTMv5.1: Software for the spatial and space–time scan statistics. Information Management Services 2004 Inc. http://www.SatScan.org/S.

  38. Song C, Kulldorff M. Power evaluation of disease clustering tests. Int J Health Geogr. 2003;2(1):9.

    Article  PubMed  Google Scholar 

  39. Kaatsch P, Spix C, Schulze-Rath R, Schmiedel S, Blettner M. Leukaemia in young children living in the vicinity of German nuclear power plants. Int J Cancer. 2008;122(4):721–6.

    Article  CAS  PubMed  Google Scholar 

  40. Spix C, Schmiedel S, Kaatsch P, Schulze-Rath R, Blettner M. Case–control study on childhood cancer in the vicinity of nuclear power plants in Germany 1980–2003. Eur J Cancer. 2008;44(2):275–84.

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank Claudia Spix and Irene Jung at the German Childhood Cancer Registry for extracting data. We also thank Jørgen Olsen and Finn Diderichsen for the support and Richard Feltbower for the useful discussion on methodology. Sven Schmiedel is supported by an international PhD stipend from the The Danish Strategic Research Council (Grant number 645-06-0479).

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Authors and Affiliations

  1. Institute for Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, 2100, Copenhagen, Denmark

    Sven Schmiedel & Joachim Schüz

  2. Institute for Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Centre of the Johannes Gutenberg-University Mainz, 55101, Mainz, Germany

    Sven Schmiedel & Maria Blettner

  3. German Childhood Cancer Registry, Institute for Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Centre of the Johannes Gutenberg-University Mainz, 55101, Mainz, Germany

    Peter Kaatsch

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  1. Sven Schmiedel
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Correspondence to Sven Schmiedel.

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Schmiedel, S., Blettner, M., Kaatsch, P. et al. Spatial clustering and space–time clusters of leukemia among children in Germany, 1987–2007. Eur J Epidemiol 25, 627–633 (2010). https://doi.org/10.1007/s10654-010-9488-7

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  • DOI: https://doi.org/10.1007/s10654-010-9488-7

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