Regular Article

BJC Open article

British Journal of Cancer (1999) 80, 585–590. doi:10.1038/sj.bjc.6690395
Published online 9 April 1999

Association of childhood leukaemia with factors related to the immune system

J Schüz1, U Kaletsch1, R Meinert1, P Kaatsch1 and J Michaelis1

1Institut für Medizinische Statistik und Dokumentation der Johannes Gutenberg-Universtität Mainz, D-55101 Mainz, Germany

Received 1 May 1998; Revised 30 October 1998; Accepted 11 November 1998



The childhood peak of common acute lymphoblastic leukaemia has been proposed as being a rare response to delayed exposure to a common infection. In this context, factors related to the child’s immune system are of special interest. Information on such factors was obtained in a recent German case-control study comprising more than 1000 children with acute leukaemia. Neither being the first-born child, nor a short duration of breastfeeding, indicators of a deficit in viral contacts during infancy or the number of infectious diseases, were significant risk factors. We observed a strong association with fewer routine immunizations with a 3.2-fold increase for those children getting less than four immunizations, but this association could partly be explained by reporting bias. While tonsillectomy or appendectomy increased the risk of leukaemia in our studies, a protective effect of allergies could be seen. In summary, we found only weak support for the delayed exposure hypothesis. To some extent this may be due to the chosen surrogate markers which reflect, rather indirectly, immunological isolation in infancy and delayed exposure to common viruses. However, the significant findings for routine immunizations, tonsillectomy and allergies of the child or its parents merit further investigation.


case-control study; childhood leukaemia; Germany; immune system; infections



  1. Alexander, F. (1997). Is mycoplasma pneunomia associated with childhood acute lymphoblastic leukemia? Cancer Causes Control 8: 803–811.
  2. Brookmeyer, R., Liang, K. Y. & Linet, M. (1986). Matched case-control designs and overmatched analyses. Am J Epidemiol 124: 693–701.
  3. Buckley, J. D., Buckley, C. M., Ruccione, K., Sather, H. N., Waskerwitz, M. J., Woods, W. G. & Robison, L. L. (1994). Epidemiological characteristics of childhood acute lymphocytic leukemia. Analysis by immunophenotype. The Children’s Cancer Group. Leukemia 8: 856–864. | PubMed | CAS |
  4. Daniels, S. E., Bhattacharrya, S., James, A., Leaves, N. I., Young, A., Hill, M. R., Faux, J. A., Ryan, G. F., le Souef, P. N., Lathrop, G. M., Musk, A. W. & Cookson, W. O. (1996). A genome-wide search for quantitative trait loci underlying asthma. Nature 383: 247–250. | Article | PubMed | ISI | CAS |
  5. Greaves, M. F. (1988). Speculations on the cause of childhood acute lymphoblastic leukemia. Leukemia 2: 120–125. | PubMed | ISI | CAS |
  6. Greaves, M. F. (1997). Aetiology of acute leukaemia. Lancet 349: 344–349. | Article | PubMed | ISI | CAS |
  7. Greaves, M. F. & Alexander, F. E. (1993). An infectious etiology for common acute lymphoblastic leukemia in childhood? Leukemia 7: 349–360. | PubMed | ISI | CAS |
  8. Hartley, A. L., Birch, J. M., McKinney, P. A., Blair, V., Teare, M. D., Carrette, J., Mann, J. R., Stiller, C. A., Draper, G. J. & Johnston, H. E. (1988). The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC): past medical history in children with cancer. J Epidemiol Community Health 42: 235–242.
  9. Kaatsch, P., Haaf, G. & Michaelis, J. (1995). Childhood malignancies in Germany – methods and results of a nationwide registry. Eur J Cancer 31A: 993–999.
  10. Kaatsch, P., Kaletsch, U., Krummenauer, F., Meinert, R., Miesner, A., Haaf, G. & Michaelis, J. (1996). Case control study on childhood leukemia in Lower Saxony, Germany. Basic considerations, methodology, and summary of results. Klin Pädiatr 208: 179–185. | Article | PubMed | CAS |
  11. Kaatsch, P., Kaletsch, U., Meinert, R., Miesner, A., Hoisl, M., Schüz, J. & Michaelis, J. (1998). German case control study on childhood leukemia – basic considerations, methodology, and summary of the results. Klin Pädiatr 210: 185–191.
  12. Kneale, G. W., Stewart, A. M. & Wilson, L. M. (1986). Immunizations against infectious diseases and childhood cancers. Cancer Immunol Immunother 21: 129–132.
  13. McMahon, B. & Newill, V. A. (1962). Birth characteristics of children dying of malignant neoplasms. J Natl Cancer Inst 28: 231–244. | PubMed | CAS |
  14. Meinert, R., Kaatsch, P., Kaletsch, U., Krummenauer, F., Miesner, A. & Michaelis, J. (1996). Childhood leukaemia and exposure to pesticides: results of a case-control study in northern Germany. Eur J Cancer 32A: 1943–1948.
  15. Michaelis, J., Keller, B., Haaf, G. & Kaatsch, P. (1992). Incidence of childhood malignancies in the vicinity of west German nuclear power plants. Cancer Causes Control 3: 255–263. | Article | PubMed | ISI | CAS |
  16. Michaelis, J., Schüz, J., Meinert, R., Menger, M., Grigat, J. P., Kaatsch, P., Kaletsch, U., Miesner, A., Stamm, A., Brinkmann, K. & Kärner, H. (1997). Childhood leukemia and electromagnetic fields: results of a population-based case control study in Germany. Cancer Causes Control 8: 167–174.
  17. Nishi, M. & Miyake, H. (1989). A case-control study of non-T cell acute lymphoblastic leukaemia of children in Hokkaido, Japan. J Epidemiol Community Health 43: 352–355.
  18. Petridou, E., Kassimos, D., Kalmanti, M., Kosmidis, H., Haidas, S., Flytzani, V., Tong, D. & Trichopoulos, D. (1993). Age of exposure to infections and risk of childhood leukaemia. Br Med J 307: 774
  19. Petridou, E., Trichopoulos, D., Kalapothaki, V., Pourtsidis, A., Kogevinas, M., Kalmanti, M., Koliouskas, D., Kosmidis, H., Panagiotou, J. P., Piperopoulou, F. & Tzortzatou, F. (1997). The risk profile of childhood leukemia in Greece: a nationwide case-control study. Br J Cancer 76: 1241–1247. | Article | PubMed | ISI | CAS |
  20. Pui, C. (1995). Childhood leukemias. N Engl J Med 332: 1618–1630. | Article | PubMed | ISI | CAS |
  21. Robison, L. L., Codd, M., Gunderson, P., Neglia, J. P., Smithson, W. A. & King, F. L. (1987). Birth weight as a risk factor for childhood acute lymphoblastic leukemia. Pediatr Hematol Oncol 4: 63–72. | PubMed | CAS |
  22. Ross, J. A., Potter, J. D., Shu, X-O, Reaman, G. H., Lampkin, B. & Robison, L. L. (1997). Evaluating the relationships among maternal reproductive history, birth characteristics, and infant leukemia: a report from the Children’s Cancer Group. Ann Epidemiol 7: 172–179. | Article | PubMed | CAS |
  23. Shu, X. O., Gao, Y. T., Brinton, L. A., Linet, M. S., Tu, J. T., Zheng, W. & Fraumeni, J. F. (1988). A population-based case-control study of childhood leukemia in Shanghai. Cancer 62: 635–644. | Article | PubMed | CAS |
  24. Shu, X. O., Clemens, J., Zheng, W., Ying, D. M., Ji, B. T. & Jin, F. (1995). Infant breastfeeding and the risk of childhood lymphoma and leukaemia. Int J Epidemiol 24: 27–32. | PubMed | CAS |
  25. Stark, C. R. & Mantel, N. (1966). Effects of maternal age and birth order on the risk of mongolism and leukemia. J Natl Cancer Inst 37: 687–698. | PubMed |
  26. Van Duijn, C. M., Van Steensel-Moll, H. A., Van der Does vd Berg, A., Van Wering, E. R., Van Zanen, G. E., Valkenburg, H. A. & Rammeloo, J. A. (1988). Infant feeding and childhood cancer. Lancet 2: 796–797. | PubMed | CAS |
  27. Van Steensel-Moll, H. A., Valkenburg, H. A., Vandenbroucke, J. P. & Van Zanen, G. E. (1986). Are maternal fertility problems related to childhood leukaemia? Int J Epidemiol 14: 555–559.
  28. Zheng, W., Linet, M. S., Shu, X. O., Pan, R. P., Gao, Y. T. & Fraumeni, J. F. Jr (1993). Prior medical conditions and the risk of adult leukemia in Shanghai, People’s Republic of China. Cancer Causes Control 4: 361–368. | Article | PubMed | ISI | CAS |
BJC Open article

From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License.
To view a copy of this license, visit