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Epidemiology

Childhood cancer research in oxford III: The work of CCRG on ionising radiation

British Journal of Cancervolume 119pages771778 (2018) | Download Citation

Abstract

Background

High doses of ionising radiation are a known cause of childhood cancer and great public and professional interest attaches to possible links between childhood cancer and lower doses, particularly of man-made radiation. This paper describes work done by the Childhood Cancer Research Group (CCRG) on this topic

Methods

Most UK investigations have made use of the National Registry of Childhood Tumours and associated controls. Epidemiological investigations have included national incidence and mortality analyses, geographical investigations, record linkage and case-control studies. Dosimetric studies use biokinetic and dosimetric modelling.

Results

This paper reviews the work of the CCRG on the association between exposure to ionising radiation and childhood cancer, 1975–2014.

Conclusion

The work of CCRG has been influential in developing understanding of the causes of 'clusters' of childhood cancer and the risks arising from exposure to ionising radiation both natural and man-made. Some clusters around nuclear installations have certainly been observed, but ionising radiation does not seem to be a plausible cause. The group’s work has also been instrumental in discounting the hypothesis that paternal preconception irradiation was a cause of childhood cancers and has demonstrated an increased leukaemia risk for children exposed to higher levels of natural gamma-ray radiation.

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Note: This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License.)

References

  1. 1.

    Bithell J. F., Draper G. J., Sorahan T., Stiller C. A. Childhood Cancer Research in Oxford I: The Oxford Survey of Childhood Cancers. Br J Cancer 2018; Submitted.

  2. 2.

    Draper G. J., et al Childhood Cancer Research in Oxford II: The Childhood Cancer Research Group. Br J Cancer 2018; Submitted.

  3. 3.

    United Nations Scientific Committee on the Effects of Atomic Radiation. Sources, Effects and Risks of Ionising radiation. UNSCEAR 2016 Report to the General Assembly, with Scientific Annexes. United Nations, New York, 2013.

  4. 4.

    Bithell, J. F. & Stewart, A. M. Pre-natal irradiation and childhood malignancy: a review of British data from the Oxford Survey. Br. J. Cancer 31, 271–287 (1975).

  5. 5.

    Berrington de Gonzalez, A. et al. Relationship between paediatric CT scans and subsequent risk of leukaemia and brain tumours: assessment of the impact of underlying conditions. Br. J. Cancer 114, 388–394 (2016).

  6. 6.

    Smith, G. M. What is a low dose? J. Radiol. Prot. 30, 93–94 (2010).

  7. 7.

    Oatway, W. B., Jones, A. L., Holmes, S., Watson, S. & Cabianca, T. PHE-CRCE-026: Ionising Radiation Exposure of the UK Population: 2010 Review. (CRCE, Public Health England, Chilton, 2016).

  8. 8.

    Webb, G. A. M., Anderson, R. W. & Gaffney, M. J. S. Classification of events with an off-site radiological impact at the Sellafield site between 1950 and 2000, using the International Nuclear Event Scale. J. Radiol. Prot. 26, 33–49 (2006).

  9. 9.

    Arnold, L. Windscale 1957 Anatomy of a Nuclear Accident. Third Edition, (Palgrave Macmillan, Basingstoke, 2007).

  10. 10.

    Black, D. Investigation of the Possible Increased Incidence of Cancer in West Cumbria. Report of the Independent Advisory Group. (HMSO, London, 1984).

  11. 11.

    Heasman, M. A., Kemp, I. W., Urquhart, J. D. & Black, R. Childhood leukaemia in northern Scotland. Lancet 327, 266 (1986).

  12. 12.

    Laurier, D. et al. Epidemiological studies of leukaemia in children and young adults around nuclear facilities: a critical review. Radiat. Prot. Dosim. 132, 182–190 (2008).

  13. 13.

    Committee on Medical Aspects of Radiation in the Environment (COMARE). Second Report. Investigation of the possible increased incidence of leukaemia in young people near the Dounreay Nuclear Establishment, Caithness, Scotland. (HMSO, London, 1988). 1988.

  14. 14.

    Grufferman, S. Clustering and aggregation of exposures in Hodgkins disease. Cancer causes & control: CCC 39, (1829–1833 (1977).

  15. 15.

    Glass, A. G., Hill, J. A. & Miller, R. W. Significance of leukemia clusters. J. Pediatr. 73, 101–107 (1968).

  16. 16.

    Stather, J. R., Wrixon, A. D. & Simmonds, J. R. NRPB-R171: The risk of leukaemia and other cancers in Seascale from radiation exposure. (National Radiological Protection Board: Chilton, UK, 1986.

  17. 17.

    Simmonds, J. R., Robinson, C. A., Phipps, A., Muirhead, C. R. I. & Fry, F. A. NRPB R276: Risks of leukaemia and other cancers in Seascale from all sources of ionising radiation exposure. (HMSO, London, 1995). 1995.

  18. 18.

    Committee on Medical Aspects of Radiation in the Environment (COMARE). Fourth Report. The incidence of cancer and leukaemia in young people in the vicinity of the Sellafield site, West Cumbria: Further studies and an update of the situation since the publication of the report of the Black Advisory Group in 1984. (Department of Health, Wetherby, 1996). 1996.

  19. 19.

    Draper, G. J., Stiller, C. A., Cartwright, R. A., Craft, A. W., & Vincent, T. J. Cancer in Cumbria and in the vicinity of the Sellafield nuclear installation, 1963–90. Br. Med. J. 306, 89–94 (1993).

  20. 20.

    Bithell, J. F., Dutton, S. J., Draper, G. J. & Neary, N. M. Distribution of childhood leukaemias and non-Hodgkin’s lymphomas near nuclear installations in England and Wales. BMJ 309, 501–505 (1994).

  21. 21.

    Committee on Medical Aspects of Radiation in the Environment (COMARE). COMARE 10th report: the incidence of childhood cancer around nuclear installations in Great Britain. (Health Protection Agency, Chilton, Didcot, 2005). 9/2005.

  22. 22.

    Evrard, A.-S. et al. Childhood leukaemia incidence around French nuclear installations using geographic zoning based on gaseous discharge dose estimates. Br. J. Cancer 94, 1342–1347 (2006).

  23. 23.

    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 122, 721–726 (2008).

  24. 24.

    Spycher, B. D. et al. Childhood cancer and nuclear power plants in Switzerland: a census-based cohort study. Int. J. Epidemiol. 40, 1247–1260 (2011).

  25. 25.

    Grosche, B., Kaatsch, P., Heinzow, B. & Wichmann, H. E. The Krümmel (Germany) Childhood Leukaemia Cluster: a review and update. J. Radiol. Prot. 37, R43 (2017).

  26. 26.

    Bithell, J. F., Keegan, T. J., Kroll, M. E., Murphy, M. F. G. & Vincent, T. J. Childhood leukaemia near British Nuclear installations: methodological issues and recent results. Radiat. Prot. Dosim. 132, 191–197 (2008).

  27. 27.

    Bithell, J. F., Keegan, T. J., Kroll, M. E., Murphy, M. F. G. & Vincent, T. J. Response to Korblein and Fairlie: correction and extensions to the calculation in “childhood leukaemia near British Nuclear Installations: methodology issues and recent results”. Radiat. Prot. Dosim. 138, 89–91 (2010).

  28. 28.

    Committee on Medical Aspects of Radiation in the Environment (COMARE). COMARE 14th report: Further consideration of the incidence of childhood leukaemia around nuclear power plants in Great Britain. (Chilton, Didcot, 2011).

  29. 29.

    Bithell, J. F. et al. Leukaemia in young children in the vicinity of British nuclear power plants: a case-control study. Br. J. Cancer 109, 2880–2885 (2013).

  30. 30.

    Bunch, K. J. et al. Updated investigations of cancer excesses in individuals born or resident in the vicinity of Sellafield and Dounreay. Br. J. Cancer 111, 1814–1823 (2014).

  31. 31.

    Fairlie, I. A hypothesis to explain childhood cancers near nuclear power plants. J. Environ. Radioact. 133(Supplement C), 10–17 (2014).

  32. 32.

    Wakeford, R., Darby, S. C. & Murphy, M. F. G. Temporal trends in childhood leukaemia incidence following exposure to radioactive fallout from atmospheric nuclear weapons testing. Radiat. Environ. Biophys. 49, 213–227 (2010).

  33. 33.

    UNSCEAR. United Nations Scientific Committee on the Effects of Atomic Radiation 2008 Report. Annex D. Health Effects due to radiation from the Chernobyl accident. (United Nations, New York, 2010).

  34. 34.

    Cardis, E. et al. Cancer consequences of the Chernobyl accident: 20 years on. J. Radiol. Prot. 26, 127–140 (2006).

  35. 35.

    Parkin, D. M. et al. Childhood leukaemia in Europe after Chernobyl: 5 year follow-up. Br. J. Cancer 73, 1006–1012 (1996).

  36. 36.

    Committee on Medical Aspects of Radiation in the Environment (COMARE). COMARE 15th report: Radium contamination in the area around Dalgety Bay. (Chilton, Didcot, OX11 0RQ, 2014).

  37. 37.

    Bithell, J. F. & Draper, G. J. Uranium-235 and childhood leukaemia around Greenham Common airfield. J. Radiol. Prot. 19, 253–259 (1999).

  38. 38.

    Gardner, M. J. et al. Results of case-control study of leukaemia and lymphoma among young people near Sellafield nuclear plant in West Cumbria. Br. Med. J. 300, 423–429 (1990).

  39. 39.

    Draper, G. J. An overview of reports and current research concerning childhood leukaemia and cancer around nuclear installations in the UK. Sci. Total Environ. 127, 9–12 (1992).

  40. 40.

    Stewart, A., Webb, J. & Hewitt, D. A survey of childhood malignancies. Br. Med. J. 1, 1495–1508 (1958).

  41. 41.

    Kinlen, L. J., Clarke, K. & Balkwill, A. Paternal preconceptional radiation exposure in the nuclear industry and leukaemia and non-Hodgkin’s lymphoma in young people in Scotland. Br. Med. J. 306, 1153–1158 (1993).

  42. 42.

    Draper, G. J. et al. Cancer in the offspring of radiation workers: a record linkage study. Br. Med. J. 315, 1181–1188 (1997).

  43. 43.

    Sorahan, T. et al. Cancer in the offspring of radiation workers: an investigation of employment timing and a reanalysis using updated dose information. Br. J. Cancer 89, 1215–1220 (2003).

  44. 44.

    Draper, G. J. et al. NRPB-R298: Cancer in the Offspring of Radiation Workers - a Record Linkage Study. (NRPB, Didcot, 1997). NRPB-R298ed.

  45. 45.

    Bunch, K. J. et al. Cancer in the offspring of female radiation workers: a record linkage study. Br. J. Cancer 100, 213–218 (2009).

  46. 46.

    Kendall, G. M. & Smith, T. J. Doses from radon and its decay products to children. J. Radiol. Prot. 25, 241–256 (2005).

  47. 47.

    Kendall, G. M., Hughes, J. S., Oatway, W. B. & Jones, A. L. Variations in radiation exposures of adults and children in the UK. J. Radiol. Prot. 26, 257–276 (2006).

  48. 48.

    Kendall, G. M. & Phipps, A. W. Effective and organ doses from thoron decay products at different ages. J. Radiol. Prot. 27, 427–435 (2007).

  49. 49.

    Kendall, G. M., Fell, T. P. & Harrison, J. D. Dose to red bone marrow of infants, children and adults from radiation of natural origin. J. Radiol. Prot. 29, 123–138 (2009).

  50. 50.

    Kendall, G. M. & Fell, T. P. Doses to the red bone marrow of young people and adults from radiation of natural origin. J. Radiol. Prot. 31, 329–335 (2011).

  51. 51.

    Wakeford, R., Kendall, G. M. & Little, M. P. The proportion of childhood leukaemia incidence in Great Britain that may be caused by natural background ionizing radiation. Leukemia 23, 770–776 (2009).

  52. 52.

    Little, M. P., Wakeford, R. & Kendall, G. M. Updated estimates of the proportion of childhood leukaemia incidence in Great Britain that may be caused by natural background ionising radiation. J. Radiol. Prot. 29, 467–482 (2009).

  53. 53.

    Kendall, G. M., Little, M. P. & Wakeford, R. Numbers and proportions of leukemias in young people and adults induced by radiation of natural origin. Leuk. Res. 35, 1039–1043 (2011).

  54. 54.

    Wakeford, R., Little, M. P. & Kendall, G. M. Risk of childhood leukemia after low-level exposure to ionizing radiation. Expert Rev. Hematol. 3, 251–254 (2010).

  55. 55.

    Little, M. P., Wakeford, R., Lubin, J. H. & Kendall, G. M. The statistical power of epidemiological studies analyzing the relationship between exposure to ionizing radiation and cancer, with special reference to childhood leukemia and natural background radiation. Radiat. Res. 174, 387–402 (2010).

  56. 56.

    Kendall, G. M. et al. Levels of naturally occurring gamma radiation measured in British homes and their prediction in particular residences. Radiat. Environ. Biophys. 55, 103–124 (2016).

  57. 57.

    Morgenstern, H. Ecologic studies in epidemiology: concepts, principles and methods. Annu. Rev. Public Health 16, 61–81 (1995).

  58. 58.

    Muirhead, C. R., Butland, B. K., Green, B. M. R. & Draper, G. J. Childhood leukaemia and natural radiation. Lancet 337, 503–504 (1991).

  59. 59.

    Muirhead, C. R., Butland, B. K., Green, B. M. R. & Draper, G. J. An analysis of childhood leukaemia and natural radiation in Britain. Radiat. Prot. Dosim. 45, 657–660 (1992).

  60. 60.

    Richardson, S., Monfort, C., Green, M., Draper, G. J. & Muirhead, C. Spatial variation of natural radiation and childhood leukaemia incidence in Great Britain. Stat. Med. 14, 2487–2501 (1995).

  61. 61.

    Kendall, G. M. et al. A record-based case-control study of natural background radiation and the incidence of childhood leukaemia and other cancers in Great Britain during 1980–2006. Leukemia 27, 3–9 (2013).

  62. 62.

    Kendall, G. M. et al. Report of a record-based case-control study of natural background radiation and incidence of childhood cancer in Great Britain. (Health Protection Agency, Chilton,Didcot, 2013). 2013.

  63. 63.

    Carstairs, V. & Morris, R. Deprivation and Health in Scotland. (Aberdeen University Press, Aberdeen, 1991).

  64. 64.

    Wrixon, A. D. et al. NRPB-R190. Natural radiation exposure in UK dwellings. (National Radiological Protection Board, Chilton,Didcot,Oxon, 1988). 1988.

  65. 65.

    Miles, J. C. H. & Appleton, J. D. Mapping variation in radon potential both between and within geological units. J. Radiol. Prot. 25, 257–276 (2005).

  66. 66.

    Pearce, M. S. et al. Radiation exposures from CT scans in childhood and subsequent risk of leukaemia and brain tumours, an historical cohort study. Lancet 380, 499–505 (2012).

  67. 67.

    Hawkins, M. M., Draper, G. J. & Kingston, J. E. Incidence of second primary tumours among childhood cancer survivors. Br. J. Cancer 56, 339–347 (1987).

  68. 68.

    Hawkins, M. M. et al. Radiotherapy, alkylating agents, and risk of bone cancer after childhood cancer. J. Natl. Cancer Inst. 88, 270–278 (1996).

  69. 69.

    Hawkins, M. M. et al. Epipodophyllotoxins, alkylating agents, and radiation and risk of secondary leukaemia after childhood cancer. Br. Med. J. 304, 951–958 (1992).

  70. 70.

    Little, M. P., Hawkins, M. M., Shore, R. E., Charles, M. W. & Hildreth, N. G. Time variations in the risk of cancer following irradiation in childhood. Radiat. Res. 126, 304–316 (1991).

  71. 71.

    Little, M. P., de Vathaire, F., Charles, M. W., Hawkins, M. M. & Muirhead, C. R. Variations with time and age in the relative risks of solid cancer incidence after radiation exposure. J. Radiol. Prot. 17, 159–177 (1997).

  72. 72.

    Hawkins, M. M. et al. The British Childhood Cancer Survivor Study: objectives, methods, population structure, response rates and initial descriptive information. Pediatr. Blood. Cancer 50, 1018–1025 (2008).

  73. 73.

    Hamlet, R. A brief history of the Committee on Medical Aspects of Radiation in the Environment (COMARE). (COMARE Secretariat, Chilton, Didcot, 2011).

  74. 74.

    Smith, G. Review of COMARE’s 17th Report. J. Radiol. Prot. 37, 558–563 (2017).

  75. 75.

    Greaves, M. F. Speculations on the cause of childhood acute lymphoblastic leukemia. Leukemia 2, 120–125 (1988).

  76. 76.

    Kinlen, L. J. Evidence for an infective cause of childhood leukaemia: comparison of a Scottish new town with nuclear reprocessing sites in Britain. Lancet 332, 1323–1327 (1988).

  77. 77.

    McNally, R. J. Q. & Eden, T. O. B. An infectious aetiology for childhood acute leukaemia: a review of the evidence. Br. J. Haematol. 127, 243–263 (2004).

  78. 78.

    Bithell J. F. Leukemia clusters. 2014. http://onlinelibrary.wiley.com/doi/10.1002/9781118445112.stat05297/full. Last accessed date on 23 July 2018.

  79. 79.

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

  80. 80.

    Greaves, M. F. & Alexander, F. E. An infectious etiology for common acute lymphoblastic leukemia in childhood? Leukemia 7, 349–360 (1993).

  81. 81.

    Gilham, C. et al. Day care in infancy and risk of childhood acute lymphoblastic leukaemia: findings from UK case-control study. BMJ 330, 1294–1297 (2005).

  82. 82.

    Kinlen, L. J. An examination, with a meta-analysis, of studies of childhood leukaemia in relation to population mixing. Br. J. Cancer 107, 1163–1168 (2012).

  83. 83.

    Committee on Medical Aspects of Radiation in the Environment (COMARE). Seventeenth Report: Further consideration of the incidence of cancers around the nuclear installations at Sellafield and Dounreay. (Public Health England, Chilton, Didcot, Oxon, 2016).

  84. 84.

    Kinlen, L. J. Epidemiological evidence for an infective basis in childhood leukaemia. Br. J. Cancer 71, 1–5 (1995).

  85. 85.

    Stiller, C. A. & Boyle, P. J. Effect of population mixing and socioeconomic status in England and Wales, 1979-85, on lymphoblastic leukaemia in children. Br. Med. J. 313, 1297–1300 (1996).

  86. 86.

    Stiller, C. A., Kroll, M. E., Boyle, P. J. & Feng, Z. Population mixing, socioeconomic status and incidence of childhood acute lymphoblastic leukaemia in England and Wales: analysis by census ward. Br. J. Cancer 98, 1006–1011 (2008).

  87. 87.

    Dickinson, H. O. & Parker, L. Quantifying the effect of population mixing on childhood leukaemia risk: the Seascale cluster. Br. J. Cancer 81, 144–151 (1999).

  88. 88.

    Dickinson, H. O., Hammal, D. M., Bithell, J. F. & Parker, L. Population mixing and childhood leukaemia and non-Hodgkin’s lymphoma in census wards in England and Wales, 1966-87. Br. J. Cancer 86, 1411–1413 (2002).

  89. 89.

    Doll, R. The epidemiology of childhood leukaemia. J. R. Stat. Soc. Ser. A. Stat. Soc. 152, 341–351 (1989).

  90. 90.

    Greaves, M. F., Pegram, S. M. & Chan, L. C. Collaborative group study of the epidemiology of acute lymphoblastic leukaemia subtypes: background and first report. Leuk. Res. 9, 715–733 (1985).

  91. 91.

    Stewart, A. Aetiology of childhood malignancies congenitally determined leukaemias. Br. Med. J. 1, 452–460 (1961).

  92. 92.

    Stewart, A. & Kneale, G. W. Role of local infections in the recognition of haemopoietic neoplasms. Nature 223, 741–742 (1969).

  93. 93.

    Kroll, M. E., Stiller, C. A., Richards, S., Mitchell, C. & Carpenter, L. M. Evidence for under-diagnosis of childhood acute lymphoblastic leukaemia in poorer communities within Great Britain. Br. J. Cancer 106, 1556–1559 (2012).

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Acknowledgements

The work of the Childhood Cancer Research Group has involved collaboration with many colleagues in the UK and abroad. There are far too many to list individually, but we would like to record our thanks to them all.

Author contributions

All authors contributed to the planning, writing and/or revision of this paper.

Author information

Affiliations

  1. Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Oxford, OX3 7LF, UK

    • Gerald M. Kendall
  2. Department of Statistics, University of Oxford, 24-29 St Giles’, Oxford, OX1 3LB, UK

    • John F. Bithell
    •  & Gerald J. Draper
  3. National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Oxford, OX3 7LF, UK

    • Kathryn J. Bunch
    •  & Mary E. Kroll
  4. Formerly of Childhood Cancer Research Group, University of Oxford, Oxford, UK

    • Tim J. Vincent
  5. Nuffield Department of Women’s and Reproductive Health John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK

    • Michael F. G. Murphy
  6. National Cancer Registration and Analysis Service, Public Health England, Chancellor Court, Oxford Business Park South, Oxford, OX4 2GX, UK

    • Charles A. Stiller

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Competing interests

The authors declare no competing interests.

Funding

The work of the CCRG was supported by the Department of Health for England and Wales and the Scottish Government. Funding also came from CHILDREN with CANCER (UK), Cancer Research UK, the Leukaemia Research Fund, The Kay Kendall Leukaemia Research Fund, The Health and Safety Executive and the National Cancer Institute (USA).

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This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

Corresponding author

Correspondence to Gerald M. Kendall.

Appendix

Appendix

Infective mechanisms and clusters of childhood leukaemia

Two main hypotheses concerning infectious mechanisms in the aetiology of childhood leukaemia have been advanced: Greaves’s Delayed Infection hypothesis75 and Kinlen’s Population Mixing Hypothesis76. The Population Mixing Hypothesis has been extended by other researchers. In addition it has been suggested by workers from CCRG that under-diagnosis of childhood leukaemia, varying both with calendar period and with SES might play a role.

The steady increase in support for these infection-based hypotheses and the dwindling of support for alternatives has left them as widely regarded as the most plausible explanations for clustering and as responsible for many features of childhood leukaemia. However, the available evidence does not allow a clear choice between them. McNally and Eden reviewed the evidence77 and concluded 'It is very important to realize that the Greaves (1988) and Kinlen population mixing hypotheses are not mutually exclusive. Elements of both may be involved in individual cases.'

For more recent reviews of clustering see ref.2,78.

Greaves’s delayed infection hypothesis

Greaves suggested that precursor B-cell Acute Lymphoblastic Leukaemia might require two independent mutations75,79. Infection was postulated to have a crucial role in promoting, through the immune response, the crucial second or postnatal genetic error. Greaves pointed out that absence or diminution of infections early in life is a feature of more affluent ‘hygienic’ societies. This has produced substantial benefits in terms of reduced infant mortality. However, such infectious insulation might predispose the immune system to aberrant or pathological responses following subsequent or ‘delayed’ exposure.

Greaves and Alexander80 published a comprehensive review of theories of an infectious aetiology for childhood leukaemia. The Greaves hypothesis receives support from, for example, an investigation from the UKCCS into day care in infancy and the risk of ALL81 which showed that increasing levels of social activity were associated with consistent reductions in risk of ALL.

Kinlen’s population mixing hypothesis

A possible explanation for clusters of childhood leukaemia around nuclear sites (and elsewhere) has been suggested by Kinlen76,82 who proposed a population mixing hypothesis under which

  • Some childhood leukaemia is a rare response to an as yet unidentified infection;

  • Individuals in isolated or rural areas would be less likely to have been exposed to this agent in early life and would be susceptible to infection by it later;

  • Marked influxes of people into rural areas would lead to mini-epidemics of subclinical infections by this agent; such infections are mainly immunizing but in rare cases lead to childhood leukaemia.

This hypothesis does not involve ionising radiation but it is frequently discussed in the context of clusters. Several studies have been published that support this idea82 and it has been gaining acceptance83. The NRCT has provided data to test it84.

Extended population mixing hypothesis

Some studies have considered population mixing in a broader sense than that defined by Kinlen82. In Kinlen’s sense, population mixing requires striking increases of population in rural areas. These other studies examine childhood leukaemia rates in the context of variables such as immigration rates in areas where there is no such dramatic influx into an isolated rural community.

Thus Stiller and co-workers85,86 using NRCT data found increased levels of childhood leukaemia in areas with greater levels of population influx both for CDs and for Census wards. Dickinson and co-workers, using data partly from the NRCT, found elevated levels of childhood ALL in electoral wards with the highest levels of population mixing87. They applied these ideas to studies of cancers (particularly LNHL) in the children of Cumbrian nuclear workers where measures of population mixing were again associated with childhood cancer. CCRG staff were again involved in some of this work88.

Pre-emptive infection

Another way in which infection might affect childhood cancer rates, possibly including the Sellafield cluster, is that ‘pre-emptive infection’ might be a mechanism explaining increasing time trends in recorded childhood acute lymphoblastic leukaemia incidence, and relatively low rates in children from more deprived communities89,90,91,92. Under this hypothesis, acute leukaemia in children pre-disposes to fatal infection, and does not always have obvious clinical symptoms. Some children might die of such infections without leukaemia ever being diagnosed. In Britain, this would probably have been more frequent in the 1970s and 80s and in more deprived communities. Clinical evidence from the 1980s and 90s supports this suggestion in the context of the socioeconomic gradient93. Greater awareness of the possibility of cancer around nuclear installations might have resulted in a smaller chance of leukaemias being missed than in other areas and under-diagnosis is likely to have been greater in the 1960s. However, it is highly implausible that such an effect could be large enough to explain the Sellafield cluster fully.

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