Letter to the Editor | Open | Published:

Infections in early life and risk of childhood ALL

British Journal of Cancer volume 100, page 863 (10 March 2009) | Download Citation


This article has been updated


Cardwell et al (2008) report that a survey of GP records, detailing recorded infections in the first year of life, finds no evidence to support the hypothesis by Greaves (2006) that deficient infectious exposure in infancy may be a risk factor for developing the common form of childhood acute lymphoblastic leukaemia (ALL). This study therefore confirms the earlier report by Roman et al (2007). These data indeed provide no support for the hypothesis. However, the authors’ underlying premise bears examination. Nowhere in the ‘Greaves’ (‘delayed infection’) hypothesis does it state or predict that the relevant ‘protective’, infectious exposures in infancy or early childhood will necessarily elicit overt symptoms or pathology that prompt GP visitations. It is perfectly plausible that only particular, albeit common, infections are, for historical/evolutionary reasons (Greaves, 2006), competent to appropriately modulate the neonatal immune system network, and these could be essentially innocuous or ‘invisible’ infections as in the parallel ‘Old Friends’ hypothesis proposed by Rook (2007) for risk of allergies. We suspect that a large proportion of infections in infancy and early childhood are asymptomatic. Has anyone done a careful study of this? A biological measure might be more relevant for an evaluation of the hypothesis than querying GP records. The authors (Cardwell et al, 2008) also ignore a conflict of data that requires resolution. The lack of protection afforded by infectious episodes recorded in GP records is at odds with a large and growing body of data from case–control studies that indicate that attendance at playgroups in infancy is protective for childhood ALL. This latter conclusion is a consistent finding from the largest studies designed to address the question (Gilham et al, 2005; Ma et al, 2005; Kamper-Jørgensen et al, 2007). Day care attendance is an accepted surrogate indicator for all types of infections transmitted through personal contact and is currently the best test of the ‘Greaves’ hypothesis as it makes no assumptions about microbial species or associated pathology/symptoms. The authors of the recent reports (Roman et al, 2007; Cardwell et al, 2008) are correct to conclude that their data provide no support for the ‘delayed infection’ hypothesis, but neither do they negate it.

Change history

  • 16 November 2011


  1. , , , (2008) Infections in early life and childhood leukaemia risk: a UK case–control study of general practitioner records. Br J Cancer 99: 1529–1533

  2. , , , , , , , for the UKCCS Investigators (2005) Day care in infancy and risk of childhood acute lymphoblastic leukaemia: findings from a UK case–control study. BMJ 330: 1294–1297

  3. (2006) Infection, immune responses and the aetiology of childhood leukaemia. Nat Rev Cancer 6: 193–203

  4. , , , , , , (2007) Childcare in the first 2 years of life reduces the risk of childhood acute lymphoblastic leukemia. Leukemia 22: 189–193

  5. , , , , , , , (2005) Ethnic difference in daycare attendance, early infections, and risk of childhood acute lymphoblastic leukemia. Cancer Epidemiol Biomarkers Prev 14: 1928–1934

  6. , , , , , , , , (2007) Childhood acute lymphoblastic leukemia and infections in the first year of life: a report from the United Kingdom Childhood Cancer Study. Am J Epidemiol 165: 496–504

  7. (2007) The hygiene hypothesis and the increasing prevalence of chronic inflammatory disorders. Trans R Soc Trop Med Hyg 101: 1072–1074

Download references

Author information


  1. Section of Haemato-Oncology, The Institute of Cancer Research, London, UK

    • M Greaves
  2. Division of Epidemiology, School of Public Health, University of California, Berkeley, CA, USA

    • P A Buffler


  1. Search for M Greaves in:

  2. Search for P A Buffler in:

Corresponding author

Correspondence to M Greaves.

About this article

Publication history




Further reading