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Childhood cancer - risk factors

This page contains information on the risk factors for childhood cancers. Very little is known about the causes of most childhood cancers. Putative risk factors can be classified as environmental and genetic, though gene-environment interactions may also be important.

Overview 

Numerous domestic and other environmental exposures have been linked with childhood cancers, but there is only limited consistency between studies for most suspected risk factors, and many studies, particularly those involving rather few cases, have been inconclusive. The interpretation of these studies is often limited by the wide range of cancers in children,, variation in the timing of exposure to risk factors, the small number of exposed subjects in many studies and the lack of information on specific substances.

These problems have led to an increased emphasis on large national or international studies such as the UK Childhood Cancer Study (UKCCS)1 and the SEARCH collaborative study of childhood brain tumours,2 and also to the analysis of pooled data from several pre-existing studies.

section reviewed 01/11/10
section updated 01/11/10

Ionising radiation

The increased risk of childhood cancer associated with antenatal obstetric irradiation was discovered over 40 years ago.3 Since then, obstetric x-ray examination in pregnancy has been largely superseded by ultrasound examination. There is no evidence that ultrasound causes childhood cancer.

Environmental ionising radiation could be a cause of childhood cancer, especially leukaemia, although there is little evidence of any increase in leukaemia incidence attributable to fallout from the Chernobyl nuclear power plant accident in 1986.4,5

Risk of childhood leukaemia around nuclear power stations has been extensively studied, but results are inconsistent.6-9 If there is an increased risk from living close to a nuclear power plant, it is very small and likely to account for less than 1% of all childhood leukaemia cases.6

The possibility that paternal preconception exposure to ionising radiation could lead to excesses of leukaemia in the vicinity of certain nuclear installations in Britain was supported by a small case-control study in the area around the Sellafield nuclear reprocessing plant.10 A review of the evidence from two large, overlapping studies of UK radiation workers employed at Sellafield and elsewhere, however, concluded that there was unlikely to be any simple causal relationship.11-13

It has been suggested that inhalation of radon, a radioactive gas that is occurs naturally in varying concentrations, may result in irradiation of the bone marrow and thereby increase the risk of leukaemia. The UKCCS and earlier studies did not show a link between indoor radon levels and risk of childhood leukaemia,14,15 but a large French study found an increased risk of acute myeloid leukaemia with higher levels of radon in houses.16

The UKCCS and French study found no evidence to link higher levels of natural background gamma radiation with childhood cancer.16,17

section reviewed 01/11/10
section updated 01/11/10

Non-ionising radiation

There has been much public concern about the possible health effects of electromagnetic fields arising from electrical sources such as power lines and domestic wiring. Analyses of pooled data from case-control studies have shown no evidence for raised risk of childhood leukaemia with exposure to power frequency (50-60Hz) fields at the levels experienced by over 95% of children in western countries.18,19

A doubling of risk has been found at the very highest exposure levels but the reasons for this are unknown and it remains possible that it is partly due to bias or confounding factors. An increased risk of leukaemia has also been shown for children living within 200 metres of a high-voltage power line, but given that the typical electromagnetic field at this distance is lower than the background field found in the average home, it is possible that this result is due to confounding or chance.20

Excessive exposure to the ultraviolet component of sunlight increases the risk of skin cancer, predominantly in adults, and this might explain the relatively high incidence of childhood melanoma in Australia and New Zealand.21 There is no conclusive evidence that other non-ionising radiation can cause cancer.

section reviewed 01/11/10
section updated 01/11/10

Infections

Worldwide, the most important examples of childhood cancers caused by infections are Burkitt’s lymphoma, Hodgkin lymphoma and nasopharyngeal carcinoma (all associated with Epstein-Barr virus), liver carcinoma (hepatitis B) and Kaposi sarcoma (HHV8) 22 but together these associations account for a very small proportion of childhood cancer in western countries.

The early childhood peak of leukaemia incidence in affluent western populations and the persistently lower incidence in socio-economically disadvantaged groups and less developed countries generally has suggested that Acute lymphoblastic leukaemia (ALL) could be associated with an abnormal response to a common infectious agent.23

Two hypotheses suggest that abnormal response to infection has a key role in the development of leukaemia. Under the ‘delayed infection’ hypothesis, ALL can result from lack of exposure to infection and consequent failure of immune system modulation during infancy.24 This model is supported by epidemiological studies showing that children with ALL tend to have had relatively few infections in the first months of life, fewer immunisations in infancy and a shorter period of breastfeeding, and are more likely to be first born or only children.25

Under the ‘impaired herd immunity’ hypothesis, leukaemia is a rare response to a common infection in particularly susceptible children. This is supported by a series of studies in which high levels of population mixing, often (but not always) as a result of migration, were accompanied by increased incidence of leukaemia.26

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section updated 01/11/10

Allergies

Several studies have shown a reduced risk of childhood ALL for individuals reporting a history of allergies particularly eczema and hay fever.27-31

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section updated 01/11/10

Drugs and medication

There have been reports of the possible carcinogenic effects of many different drugs taken by mothers during pregnancy. The only one firmly established as a transplacental carcinogen is diethylstilboestrol (DES), a hormone which in some countries used to be given to pregnant women with threatened miscarriage.

Exposure to DES in utero caused clear cell adenocarcinoma of the vagina or cervix mostly in young women, though a few cases were observed in girls aged under 15;32 however, as its use was discontinued about 30 years ago, and there is no direct evidence for a transgenerational effect, it is unlikely that further childhood cancers attributable to DES will be seen.

Much controversy and public concern was generated by a study that found that intramuscular vitamin K given to infants to prevent vitamin K deficiency bleeding was associated with a doubling of the risk of childhood cancer.33 A pooled analysis of six case-control studies, including the one which gave rise to the controversy, found little evidence for raised risk of leukaemia or other cancer among children recorded as having received intramuscular vitamin K, though interpretation was rendered difficult by the poor quality of much of the vitamin K data.34

section reviewed 01/11/10
section updated 01/11/10

Parental occupation

Many associations have been reported between parental occupation and childhood cancer. When 48 studies were reviewed, there was rather little consistency between them, though a few biologically plausible associations found in more than one study would merit further investigation.35

The UKCCS was typical of more recent studies in finding no strong evidence to link parental occupational exposures with an increased risk of childhood cancer.36

section reviewed 01/11/10
section updated 01/11/10

Smoking

In 2009, the International Agency for Research on Cancer (IARC) classified parental smoking, during pregnancy, or during the period prior to conception, as a cause of hepatoblastoma in offspring, based on four recent studies.46 One of these studies, the UKCCS, showed the highest risk increase (almost five-fold) when both parents smoke.38 In addition, IARC stated that there is limited evidence that parental smoking increases risk of leukaemia in childhood.46 An earlier meta-analysis of more than 30 studies showed a 10% increase in risk of all neoplasms with maternal smoking during pregnancy but no evidence for an increased risk of any specific cancer.37

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section updated 01/11/10

Parental age

The evidence points to a higher risk of ALL with increasing age of either parent,25,39,40 although not all studies have shown an association.41-43

section reviewed 01/11/10
section updated 01/11/10

Birthweight

Higher birthweight is associated with an increased risk of childhood cancer overall, a large Nordic cohort study showed.[47]. Risks are increased for ALL (14% increased risk per 1kg increment in birthweight, or 24% increased risk for large versus normal for gestational age), osteosarcoma (35% risk increase for high versus average birthweight), Wilms tumour (36% increased risk for high versus average birthweight), and neuroblastoma (13% increased risk per 1kg increment above 2.5kg), meta-analyses show.44,48-51 However there appears to be no association between birthweight and lymphoma risk,49 and AML risk may be higher in children with either higher or lower than average birthweight.47,52

Low birthweight is thought to explain the increased risk of hepatoblastoma found in a British cohort study of children born following assisted conception; overall no association was found between cancer risk and being born following assisted conception.53

section reviewed 06/12/13
section updated 06/12/13

Breastfeeding

There is a very small reduction in risk of ALL in children who have been breastfed, and a slightly larger reduction for children breastfed for six months or longer.45

section reviewed 01/11/10
section updated 01/11/10

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References for childhood cancer risk factors

  1. UK Childhood Cancer Study Investigators. Childhood cancer and residential proximity to power lines. Br J Cancer 2000;83:1573-80.
  2. McCredie M, Little J, Cotton S, et al. SEARCH international case-control study of childhood brain tumours: role of index pregnancy and birth, and mother's reproductive history. Paediatr Perinat Epidemiol 1999;13:325-41.
  3. Stewart A, Webb J, Hewitt D. A survey of childhood malignancies. Br Med J 1958;1:1495-508.
  4. Parkin DM, Clayton D, Black RJ, et al. Childhood leukaemia in Europe after Chernobyl: 5 year follow-up. Br J Cancer 1996;73:1006-12.
  5. International Consortium for Research on the Health Effects of Radiation Writing Committee and Study Team, Davis S, Day RW, et al. Childhood leukaemia in Belarus, Russia, and Ukraine following the Chernobyl power station accident: results from an international collaborative population-based case-control study. Int J Epidemiol 2006;35:386-96.
  6. Spix C, Schmiedel S, Kaatsch P, et al. Case-control study on childhood cancer in the vicinity of nuclear power plants in Germany 1980-2003. Eur J Cancer 2008;44:275-84.
  7. Bithell JF, Dutton SJ, Draper GJ, et al. Distribution of childhood leukaemias and non-Hodgkin's lymphomas near nuclear installations in England and Wales. BMJ 1994;309:501-5.
  8. White-Koning ML, Hemon D, Laurier D, et al. Incidence of childhood leukaemia in the vicinity of nuclear sites in France, 1990-1998. Br J Cancer 2004;91:916-22.
  9. Mangano JJ, Sherman J, Chang C, et al. Elevated childhood cancer incidence proximate to U.S. nuclear power plants. Arch Environ Health 2003;58:74-82.
  10. Gardner MJ, Snee MP, Hall AJ, et al. Results of case-control study of leukaemia and lymphoma among young people near Sellafield nuclear plant in West Cumbria. BMJ 1990;300:423-9.
  11. Draper GJ, Little MP, Sorahan T, et al. Cancer in the offspring of radiation workers: a record linkage study. BMJ 1997;315:1181-8.
  12. Roman E, Doyle P, Maconochie N, et al. Cancer in children of nuclear industry employees: report on children aged under 25 years from nuclear industry family study. BMJ 1999;318:1443-50.
  13. Committee on Medical Aspects of Radiation in the Environment (COMARE). Seventh Report. Parents occupationally exposed to radiation prior to the conception of their children. A review of the evidence concerning the incidence of cancer in their children: National Radiological Protection Board; 2002.
  14. Laurier D, Valenty M, Tirmarche M. Radon exposure and the risk of leukemia: a review of epidemiological studies. Health Phys 2001;81:272-88.
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  16. Evrard AS, Hemon D, Billon S, et al. Childhood leukemia incidence and exposure to indoor radon, terrestrial and cosmic gamma radiation. Health Phys 2006;90:569-79.
  17. Investigators UKCCS.  The United Kingdom Childhood Cancer Study of exposure to domestic sources of ionising radiation: 2: gamma radiation. Br J Cancer 2002;86:1727-31.
  18. Greenland S, Sheppard AR, Kaune WT, et al. A pooled analysis of magnetic fields, wire codes, and childhood leukemia. Childhood Leukemia-EMF Study Group. Epidemiology 2000;11:624-34.
  19. Ahlbom A, Day N, Feychting M, et al. A pooled analysis of magnetic fields and childhood leukaemia. Br J Cancer 2000;83:692-8.
  20. Draper G, Vincent T, Kroll ME, et al. Childhood cancer in relation to distance from high voltage power lines in England and Wales: a case-control study. BMJ 2005;330:1290.
  21. A report of the Royal College of Physicians. Links between exposure to ultraviolet radiation and skin cancer. J R Coll Physicians Lond 1987;21:91-6.
  22. Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer 2006;118:3030-44.
  23. Smith MA, Simon R, Strickler HD, et al. Evidence that childhood acute lymphoblastic leukemia is associated with an infectious agent linked to hygiene conditions. Cancer Causes Control 1998;9:285-98.
  24. Greaves M. Childhood leukaemia. BMJ 2002;324:283-7.
  25. Dockerty JD, Draper G, Vincent T, et al. Case-control study of parental age, parity and socioeconomic level in relation to childhood cancers. Int J Epidemiol 2001;30:1428-37.
  26. Kinlen LJ. Epidemiological evidence for an infective basis in childhood leukaemia. Br J Cancer 1995;71:1-5.
  27. Hughes AM, Lightfoot T, Simpson J, et al.  Allergy and risk of childhood leukaemia: results from the UKCCS. Int J Cancer 2007;121:819-24.
  28. Rosenbaum PF, Buck GM, Brecher ML. Allergy and infectious disease histories and the risk of childhood acute lymphoblastic leukaemia. Paediatr Perinat Epidemiol 2005;19:152-64.
  29. Jourdan-Da Silva N, Perel Y, Mechinaud F, et al. Infectious diseases in the first year of life, perinatal characteristics and childhood acute leukaemia. Br J Cancer 2004;90:139-45.
  30. Schuz J, Morgan G, Bohler E, et al. Atopic disease and childhood acute lymphoblastic leukemia. Int J Cancer 2003;105:255-60.
  31. Wen W, Shu XO, Linet MS, et al. Allergic disorders and the risk of childhood acute lymphoblastic leukemia (United States). Cancer Causes Control 2000;11:303-7.
  32. Giusti RM, Iwamoto K, Hatch EE. Diethylstilbestrol revisited: a review of the long-term health effects. Ann Intern Med 1995;122:778-88.
  33. Golding J, Greenwood R, Birmingham K, et al. Childhood cancer, intramuscular vitamin K, and pethidine given during labour. BMJ 1992;305:341-6.
  34. Roman E, Fear NT, Ansell P, et al. Vitamin K and childhood cancer: analysis of individual patient data from six case-control studies. Br J Cancer 2002;86:63-9.
  35. Colt JS, Blair A. Parental occupational exposures and risk of childhood cancer. Environ Health Perspect 1998;106 Suppl 3:909-25.
  36. McKinney PA, Fear NT, Stockton D, Investigators UKCCS. Parental occupation at periconception: findings from the United Kingdom Childhood Cancer Study. Occup Environ Med 2003;60:901-9.
  37. Boffetta P, Tredaniel J, Greco A. Risk of childhood cancer and adult lung cancer after childhood exposure to passive smoke: A meta-analysis. Environ Health Perspect 2000;108:73-82.
  38. Pang D, McNally R, Birch JM. Parental smoking and childhood cancer: results from the United Kingdom Childhood Cancer Study. Br J Cancer 2003;88:373-81.
  39. Yip BH, Pawitan Y, Czene K. Parental age and risk of childhood cancers: a population-based cohort study from Sweden. Int J Epidemiol 2006;35:1495-503.
  40. Reynolds P, Von Behren J, Elkin EP. Birth characteristics and leukemia in young children. Am J Epidemiol 2002;155:603-13.
  41. Murray L, McCarron P, Bailie K, et al. Association of early life factors and acute lymphoblastic leukaemia in childhood: historical cohort study. BR J Cancer 2002;86:356-61.
  42. Shaw G, Lavey R, Jackson R, et al. Association of childhood leukemia with maternal age, birth order, and paternal occupation. A case-control study. Am J Epidemiol 1984;119:788-95.
  43. Zack M, Adami HO, Ericson A. Maternal and perinatal risk factors for childhood leukemia. Cancer Res 1991;51:3696-701.
  44. Hjalgrim LL, Westergaard T, Rostgaard K, et al. Birth weight as a risk factor for childhood leukemia: a meta-analysis of 18 epidemiologic studies. Am J Epidemiol 2003;158:724-35.
  45. Martin RM, Gunnell D, Owen CG, et al. Breast-feeding and childhood cancer: A systematic review with metaanalysis. Int J Cancer 2005;117:1020-31.
  46. Secretan B, Straif K, Baan R, et al. A review of human carcinogens--Part E: tobacco, areca nut, alcohol, coal smoke, and salted fish. Lancet Oncol 2009;10:1033-4.
  47. Bjorge T, Sorensen HT, Grotmol T, et al. Fetal growth and childhood cancer: a population-based study. Pediatrics. 2013 Nov;132(5):e1265-75.
  48. Milne E, Greenop KR, Metayer C, et al. Fetal growth and childhood acute lymphoblastic leukemia: findings from the childhood leukemia international consortium. Int J Cancer. 2013 Dec 15;133(12):2968-79.
  49. Mirabello L, Pfeiffer R, Murphy G, et al. Height at diagnosis and birth-weight as risk factors for osteosarcoma. Cancer Causes Control. 2011 Jun;22(6):899-908.
  50. Chu A, Heck JE, Ribeiro KB, et al. Wilms' tumour: a systematic review of risk factors and meta-analysis. Paediatr Perinat Epidemiol. 2010 Sep;24(5):449-69.
  51. Harder T, Plagemann A, Harder A. Birth weight and risk of neuroblastoma: a meta-analysis. Int J Epidemiol. 2010 Jun;39(3):746-56.
  52. Caughey RW, Michels KB. Birth weight and childhood leukemia: a meta-analysis and review of the current evidence. Int J Cancer. 2009 Jun 1;124(11):2658-70.
  53. Williams CL, Bunch KJ, Stiller CA, et al. Cancer risk among children born after assisted conception. N Engl J Med. 2013 Nov 7;369(19):1819-27.
Updated: 2 November 2010