Cancer Causes & Control

, 20:129 | Cite as

Infectious exposure in the first year of life and risk of central nervous system tumors in children: analysis of day care, social contact, and overcrowding

  • N. J. Harding
  • J. M. Birch
  • S. J. Hepworth
  • P. A. McKinneyEmail author
Original Paper


Little is known regarding the aetiology of central nervous system tumors in children. Recent studies have speculated on a potential infectious aetiology, but no clear associations have been found. This article uses parent reported questionnaire data from the UK Childhood Cancer Study (UKCCS), a population-based case–control study, to examine the relationship between the infectious exposure in the first year of life and the likelihood of developing a CNS tumor. The variables representing infectious exposure were social contact (including social contact with other infants and attendance at informal and formal day care), sharing a bedroom with another child, birth order, and exposure to a school-age child within the home. Children reported to have had no social contact with other infants in the first year of life displayed an increased risk of developing a CNS tumor when compared to those who had (OR 1.37, 95% CI 1.08–1.75). This effect was most prominent in the primitive neuroectodermal tumor/medulloblastoma subgroup (OR 1.78, 95% CI 1.12–2.83). Those who had attended informal (OR 0.86, 95% CI 0.68–1.09) or formal day care (OR 0.93, 95% CI 0.68–1.26) showed slightly non-statistically significant reduced risks when compared to those reporting social contact only. No association with any of the other variables was observed. Overall, the inconsistent findings by variable and tumor subtype suggest that an early exposure to infections is not strongly implicated in the aetiology of CNS tumors. However, the effect for social contact outside the home, particularly for PNET/medulloblastomas warrants further investigation.


Childhood cancer Childhood neoplasms CNS tumors Brain tumors Infectious exposure Social contact UKCCS 



UKCCS Management committee—KK Cheng, Central region; N Day, East Anglia region; R Cartwright, A Craft, North East region; JM Birch, OB Eden, North West region; PA McKinney, Scotland; J Peto, South East region; V Beral, E Roman, South Midlands region; P Elwood, South Wales region; FE Alexander, South West region; CED Chilvers, Trent region; R Doll, Epidemiological Studies Unit, University of Oxford, Oxford; CM Taylor Immunogenetics Laboratory, University of Manchester, Manchester; M Greaves, Leukaemia Research Fund Centre, Institute of Cancer Research; D Goodhead, Radiation and Genome Stability Unit, Medical Research Council, Harwell; FA Fry, National Radiological Protection Board; G Adams, UK Coordinating Committee for Cancer Research. Writing Committee—N Day, J Skinner, East Anglia region; E Roman, South Midlands region; SG Allen, MP Maslanyj, TJ Mee, National Radiological Protection Board. Regional Investigators—KK Cheng, E Gilman, Central region; N Day, J Skinner, D Williams, East Anglia region; R Carwright, A Craft, North East region; JM Birch, O B Eden, North West region; PA McKinney, Scotland; J Deacon, J Peto, South East region; V Beral, E Roman, South Midlands region; P Elwood, South Wales region; FE Alexander, M Mott, South West region; CED Chilvers, K Muir, Trent region. Leukaemia Research Fund Data Management Processing Group—R Cartwright, G Law, J Simpson, E Roman. A complete list of investigators is given in: The United Kingdom Childhood Cancer Study: objectives, material, and methods. Br J Cancer.

The UKCCS was sponsored and administered by the United Kingdom Coordinating Committee on Cancer Research and was supported by the Childhood Cancer and Leukaemia Group (formerly UKCCSG), paediatric oncologists, and by the National Radiological Protection Board. Financial support was provided by: Cancer Research UK, Leukaemia Research Fund, and Medical Research Council through grants to their units; Leukaemia Research Fund for the UKCCS data centre at the University of York; Leukaemia Research Fund, Department of Health, member companies of the Electricity Association, Irish Electricity Supply Board, National Grid Company PLC, and Westlakes Research (Trading) Ltd for general expenses of the study; Kay Kendall Leukaemia Fund for associated laboratories studies; and Foundation of Children with Leukaemia for study of electrical fields. The investigation in Scotland was funded by the Scottish Office, Scottish Power PLC, Scottish Hydro-electric plc, and Scottish Nuclear Ltd. We thank the members of the UKCCSG for their support, the staff of the local hospitals, the family physicians, and their practice staff. We especially thank the families of the children included in the study for their help. The analyses for this paper were supported by Cancer Research UK. JM Birch is a Cancer Research UK Professorial Fellow.


  1. 1.
    Linet MS, Wacholder S, Zahm SH (2003) Interpreting epidemiologic research: lessons from studies of childhood cancer. Pediatrics 112(1 Pt 2):218–232PubMedGoogle Scholar
  2. 2.
    Baldwin RT, Preston-Martin S (2004) Epidemiology of brain tumors in childhood—a review. Toxicol Appl Pharmacol 199(2):118–131. doi: 10.1016/j.taap.2003.12.029 PubMedCrossRefGoogle Scholar
  3. 3.
    Buckley JD et al (1996) Concordance for childhood cancer in twins. Med Pediatr Oncol 26(4):223–229. doi:10.1002/(SICI)1096-911X(199604)26:4<223::AID-MPO1>3.0.CO;2-LPubMedCrossRefGoogle Scholar
  4. 4.
    Bondy ML et al (1991) Genetic epidemiology of childhood brain tumors. Genet Epidemiol 8(4):253–267. doi: 10.1002/gepi.1370080406 PubMedCrossRefGoogle Scholar
  5. 5.
    Little J (1999) Epidemiology of childhood cancer, International Agency for Research on Cancer, IARC Scientific Publications No. 149. IARC Scientific Publications, LyonGoogle Scholar
  6. 6.
    McNally RJ et al (2002) An infectious aetiology for childhood brain tumours? Evidence from space-time clustering and seasonality analyses. Br J Cancer 86(7):1070–1077. doi: 10.1038/sj.bjc.6600228 PubMedCrossRefGoogle Scholar
  7. 7.
    McNally RJ et al (2004) Further clues concerning the aetiology of childhood central nervous system tumours. Eur J Cancer 40(18):2766–2772. doi: 10.1016/j.ejca.2004.08.020 PubMedCrossRefGoogle Scholar
  8. 8.
    Dickinson HO, Nyari TA, Parker L (2002) Childhood solid tumours in relation to infections in the community in Cumbria during pregnancy and around the time of birth. Br J Cancer 87(7):746–750. doi: 10.1038/sj.bjc.6600530 PubMedCrossRefGoogle Scholar
  9. 9.
    Nyari TA et al (2003) Childhood solid tumours in relation to population mixing around the time of birth. Br J Cancer 88(9):1370–1374. doi: 10.1038/sj.bjc.6600880 PubMedCrossRefGoogle Scholar
  10. 10.
    Fear NT et al (2001) Malignant neoplasms of the brain during childhood: the role of prenatal and neonatal factors (United Kingdom). Cancer Causes Control 12(5):443–449. doi: 10.1023/A:1011201524589 PubMedCrossRefGoogle Scholar
  11. 11.
    Linos A et al (1998) Reported influenza in pregnancy and childhood tumour. Eur J Epidemiol 14(5):471–475. doi: 10.1023/A:1007437200858 PubMedCrossRefGoogle Scholar
  12. 12.
    Harding NJ et al (2007) Breastfeeding and risk of childhood CNS tumours. Br J Cancer 96(5):815–817. doi: 10.1038/sj.bjc.6603638 PubMedCrossRefGoogle Scholar
  13. 13.
    Harding NJ et al (2008) Atopic dysfunction and risk of central nervous system tumours in children. Eur J Cancer 44(1):92–99. doi: 10.1016/j.ejca.2007.10.007 PubMedCrossRefGoogle Scholar
  14. 14.
    Bach JF (2002) The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med 347(12):911–920. doi: 10.1056/NEJMra020100 PubMedCrossRefGoogle Scholar
  15. 15.
    McDade TW et al (2001) Prenatal undernutrition, postnatal environments, and antibody response to vaccination in adolescence. Am J Clin Nutr 74(4):543–548PubMedGoogle Scholar
  16. 16.
    Kramer U et al (1999) Age of entry to day nursery and allergy in later childhood. Lancet 353(9151):450–454. doi: 10.1016/S0140-6736(98)06329-6 PubMedCrossRefGoogle Scholar
  17. 17.
    McKinney PA et al (2000) Early social mixing and childhood type 1 diabetes mellitus: a case–control study in Yorkshire, UK. Diabetes Med 17(3):236–242. doi: 10.1046/j.1464-5491.2000.00220.x CrossRefGoogle Scholar
  18. 18.
    Ponsonby AL et al (2005) Exposure to infant siblings during early life and risk of multiple sclerosis. JAMA 293(4):463–469. doi: 10.1001/jama.293.4.463 PubMedCrossRefGoogle Scholar
  19. 19.
    McNally RJ, Eden TO (2004) An infectious aetiology for childhood acute leukaemia: a review of the evidence. Br J Haematol 127(3):243–263. doi: 10.1111/j.1365-2141.2004.05166.x PubMedCrossRefGoogle Scholar
  20. 20.
    Hughes AM et al (2007) Allergy and risk of childhood leukaemia: results from the UKCCS. Int J Cancer 121(4):819–824. doi: 10.1002/ijc.22702 PubMedCrossRefGoogle Scholar
  21. 21.
    Wald ER et al (1988) Frequency and severity of infections in day care. J Pediatr 112(4):540–546. doi: 10.1016/S0022-3476(88)80164-1 PubMedCrossRefGoogle Scholar
  22. 22.
    Wald ER, Guerra N, Byers C (1991) Frequency and severity of infections in day care: three-year follow-up. J Pediatr 118(4 Pt 1):509–514PubMedGoogle Scholar
  23. 23.
    Louhiala PJ et al (1995) Form of day care and respiratory infections among Finnish children. Am J Public Health 85(8 Pt 1):1109–1112PubMedCrossRefGoogle Scholar
  24. 24.
    Holmes SJ, Morrow AL, Pickering LK (1996) Child-care practices: effects of social change on the epidemiology of infectious diseases and antibiotic resistance. Epidemiol Rev 18(1):10–28PubMedGoogle Scholar
  25. 25.
    Rosenbaum PF, Buck GM, Brecher ML (2000) Early child-care and preschool experiences and the risk of childhood acute lymphoblastic leukemia. Am J Epidemiol 152(12):1136–1144. doi: 10.1093/aje/152.12.1136 PubMedCrossRefGoogle Scholar
  26. 26.
    Ma X et al (2002) Daycare attendance and risk of childhood acute lymphoblastic leukaemia. Br J Cancer 86(9):1419–1424. doi: 10.1038/sj.bjc.6600274 PubMedCrossRefGoogle Scholar
  27. 27.
    Neglia JP et al (2000) Patterns of infection and day care utilization and risk of childhood acute lymphoblastic leukaemia. Br J Cancer 82(1):234–240. doi: 10.1054/bjoc.1999.0905 PubMedCrossRefGoogle Scholar
  28. 28.
    Gilham C et al (2005) Day care in infancy and risk of childhood acute lymphoblastic leukaemia: findings from UK case–control study. BMJ 330(7503):1294. doi: 10.1136/bmj.38428.521042.8F PubMedCrossRefGoogle Scholar
  29. 29.
    Chang ET et al (2004) Childhood social environment and Hodgkin’s lymphoma: new findings from a population-based case–control study. Cancer Epidemiol Biomarkers Prev 13(8):1361–1370PubMedGoogle Scholar
  30. 30.
    Menegaux F et al (2004) Day care, childhood infections, and risk of neuroblastoma. Am J Epidemiol 159(9):843–851. doi: 10.1093/aje/kwh111 PubMedCrossRefGoogle Scholar
  31. 31.
    Shaw AK, Li P, Infante-Rivard C (2006) Early infection and risk of childhood brain tumors (Canada). Cancer Causes Control 17(10):1267–1274. doi: 10.1007/s10552-006-0066-y PubMedCrossRefGoogle Scholar
  32. 32.
    UK Childhood Cancer Study Investigators (2000) The United Kingdom Childhood Cancer Study: objectives, materials and method. UK Childhood Cancer Study Investigators. Br J Cancer 82(5):1073–1102. doi: 10.1054/bjoc.1999.1045 CrossRefGoogle Scholar
  33. 33.
    Arvin AM, Koropchak CM, Wittek AE (1983) Immunologic evidence of reinfection with varicella-zoster virus. J Infect Dis 148(2):200–205PubMedGoogle Scholar
  34. 34.
    Birch JM, Marsden HB (1987) A classification scheme for childhood cancer. Int J Cancer 40(5):620–624. doi: 10.1002/ijc.2910400508 PubMedCrossRefGoogle Scholar
  35. 35.
    Fritz A (2000) International classification of diseases for oncology, vol vii, 3rd edn. World Health Organization, Geneva 240 ppGoogle Scholar
  36. 36.
    Townsend PPP, Beattie A (1988) Health and deprivation: inequality and the North. Croom Helm, LondonGoogle Scholar
  37. 37.
    Peris-Bonet R et al (2006) Childhood central nervous system tumours—incidence and survival in Europe (1978–1997): report from Automated Childhood Cancer Information System project. Eur J Cancer 42(13):2064–2080. doi: 10.1016/j.ejca.2006.05.009 PubMedCrossRefGoogle Scholar
  38. 38.
    McNally RJ et al (2001) Temporal increases in the incidence of childhood solid tumors seen in Northwest England (1954–1998) are likely to be real. Cancer 92(7):1967–1976. doi:10.1002/1097-0142(20011001)92:7<1967::AID-CNCR1716>3.0.CO;2-#PubMedCrossRefGoogle Scholar
  39. 39.
    Kleihues P, Cavenee WK, International Agency for Research on Cancer (2000) Pathology and genetics of tumours of the nervous system. IARC Press, Lyon 314 ppGoogle Scholar
  40. 40.
    McKinney PA (2005) Central nervous system tumours in children: epidemiology and risk factors. Bioelectromagnetics Suppl 7:S60–S68. doi: 10.1002/bem.20149 PubMedCrossRefGoogle Scholar
  41. 41.
    McKinney PA et al (1999) Pre- and perinatal risk factors for childhood leukaemia and other malignancies: a Scottish case control study. Br J Cancer 80(11):1844–1851. doi: 10.1038/sj.bjc.6690609 PubMedCrossRefGoogle Scholar
  42. 42.
    Linet MS et al (1996) Maternal and perinatal risk factors for childhood brain tumors (Sweden). Cancer Causes Control 7(4):437–448. doi: 10.1007/BF00052670 PubMedCrossRefGoogle Scholar
  43. 43.
    Law GR, Smith AG, Roman E (2002) The importance of full participation: lessons from a national case–control study. Br J Cancer 86(3):350–355. doi: 10.1038/sj.bjc.6600092 PubMedCrossRefGoogle Scholar
  44. 44.
    Greaves MF (1997) Aetiology of acute leukaemia. Lancet 349(9048):344–349. doi: 10.1016/S0140-6736(96)09412-3 PubMedCrossRefGoogle Scholar
  45. 45.
    Greaves MF, Alexander FE (1993) An infectious etiology for common acute lymphoblastic leukemia in childhood? Leukemia 7(3):349–360PubMedGoogle Scholar
  46. 46.
    Office for National Statistics (2003) Day care places for children. In: Summerfield C, Babb P (eds) Social trends, vol 33. HMSO, LondonGoogle Scholar
  47. 47.
    Heuch JM et al (1998) Risk of primary childhood brain tumors related to birth characteristics: a Norwegian prospective study. Int J Cancer 77(4):498–503. doi:10.1002/(SICI)1097-0215(19980812)77:4<498::AID-IJC4>3.0.CO;2-PPubMedCrossRefGoogle Scholar
  48. 48.
    Von Behren J, Reynolds P (2003) Birth characteristics and brain cancers in young children. Int J Epidemiol 32(2):248–256. doi: 10.1093/ije/dyg057 CrossRefGoogle Scholar
  49. 49.
    McCredie M et al (1999) SEARCH international case–control study of childhood brain tumours: role of index pregnancy and birth, and mother’s reproductive history. Paediatr Perinat Epidemiol 13(3):325–341. doi: 10.1046/j.1365-3016.1999.00195.x PubMedCrossRefGoogle Scholar
  50. 50.
    Strachan DP (2000) Family size, infection and atopy: the first decade of the “hygiene hypothesis”. Thorax 55(Suppl 1):S2–S10. doi: 10.1136/thorax.55.suppl_1.S2 PubMedCrossRefGoogle Scholar
  51. 51.
    Stiller CA, Nectoux J (1994) International incidence of childhood brain and spinal tumours. Int J Epidemiol 23(3):458–464. doi: 10.1093/ije/23.3.458 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • N. J. Harding
    • 1
  • J. M. Birch
    • 2
  • S. J. Hepworth
    • 1
  • P. A. McKinney
    • 1
    Email author
  1. 1.Paediatric Epidemiology Group, Centre for Epidemiology and BiostatisticsUniversity of LeedsLeedsUK
  2. 2.Cancer Research UK Paediatric and Familial Cancer Research GroupCentral Manchester and Manchester Children’s University Hospitals NHS TrustManchesterUK

Personalised recommendations