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Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 1995 Apr;32(4):251–256. doi: 10.1136/jmg.32.4.251

Leukaemia and Sellafield: is there a heritable link?

E J Tawn 1
PMCID: PMC1050370  PMID: 7643351

Abstract

The demonstration of a statistical association between paternal preconceptional irradiation and childhood leukaemia appeared to provide a satisfactory explanation for the excess of cases in the village of Seascale, close to the Sellafield nuclear installation, and became the basis of two legal claims for compensation. In the ensuing scientific debate the biological plausibility of a causal interpretation of this association focused on the heritability of leukaemia and a comparison of the genetic risks implied by this finding with current information on the induction of genetic damage by irradiation. After a wide ranging review of the mechanistic issues it is concluded that there is no genetic basis for a causal relationship and this, together with recent appraisals of epidemiological studies, suggests that the association between childhood leukaemia and paternal preconceptional irradiation exposure is most likely to be a chance finding.

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Selected References

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  1. Abrahamson S. Childhood leukemia at Sellafield. Radiat Res. 1990 Aug;123(2):237–238. [PubMed] [Google Scholar]
  2. Adams J. M., Cory S. Transgenic models of tumor development. Science. 1991 Nov 22;254(5035):1161–1167. doi: 10.1126/science.1957168. [DOI] [PubMed] [Google Scholar]
  3. Baverstock K. F. DNA instability, paternal irradiation and leukaemia in children around Sellafield. Int J Radiat Biol. 1991 Oct;60(4):581–595. doi: 10.1080/09553009114552421. [DOI] [PubMed] [Google Scholar]
  4. Brenner D. J., Hall E. J. The inverse dose-rate effect for oncogenic transformation by neutrons and charged particles: a plausible interpretation consistent with published data. Int J Radiat Biol. 1990 Nov;58(5):745–758. doi: 10.1080/09553009014552131. [DOI] [PubMed] [Google Scholar]
  5. Cosgrove G. E., Selby P. B., Upton A. C., Mitchell T. J., Steele M. H., Russell W. L. Lifespan and autopsy findings in the first-generation offspring of X-irradiated male mice. Mutat Res. 1993 Sep;319(1):71–79. doi: 10.1016/0165-1218(93)90032-9. [DOI] [PubMed] [Google Scholar]
  6. Doll R., Evans H. J., Darby S. C. Paternal exposure not to blame. Nature. 1994 Feb 24;367(6465):678–680. doi: 10.1038/367678a0. [DOI] [PubMed] [Google Scholar]
  7. Draper G. J., Heaf M. M., Kinnier Wilson L. M. Occurrence of childhood cancers among sibs and estimation of familial risks. J Med Genet. 1977 Apr;14(2):81–90. doi: 10.1136/jmg.14.2.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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. BMJ. 1993 Jan 9;306(6870):89–94. doi: 10.1136/bmj.306.6870.89. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ehling U. H. Genetic risk assessment. Annu Rev Genet. 1991;25:255–280. doi: 10.1146/annurev.ge.25.120191.001351. [DOI] [PubMed] [Google Scholar]
  10. Evans H. J. Ionising radiations from nuclear establishments and childhood leukaemias--an enigma. Bioessays. 1990 Nov;12(11):541–549. doi: 10.1002/bies.950121108. [DOI] [PubMed] [Google Scholar]
  11. Felix C. A., D'Amico D., Mitsudomi T., Nau M. M., Li F. P., Fraumeni J. F., Jr, Cole D. E., McCalla J., Reaman G. H., Whang-Peng J. Absence of hereditary p53 mutations in 10 familial leukemia pedigrees. J Clin Invest. 1992 Aug;90(2):653–658. doi: 10.1172/JCI115907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ford A. M., Ridge S. A., Cabrera M. E., Mahmoud H., Steel C. M., Chan L. C., Greaves M. In utero rearrangements in the trithorax-related oncogene in infant leukaemias. Nature. 1993 May 27;363(6427):358–360. doi: 10.1038/363358a0. [DOI] [PubMed] [Google Scholar]
  13. Gardner M. J., Hall A. J., Downes S., Terrell J. D. Follow up study of children born to mothers resident in Seascale, West Cumbria (birth cohort). Br Med J (Clin Res Ed) 1987 Oct 3;295(6602):822–827. doi: 10.1136/bmj.295.6602.822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gardner M. J., Hall A. J., Snee M. P., Downes S., Powell C. A., Terrell J. D. Methods and basic data of case-control study of leukaemia and lymphoma among young people near Sellafield nuclear plant in West Cumbria. BMJ. 1990 Feb 17;300(6722):429–434. doi: 10.1136/bmj.300.6722.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gardner M. J., Snee M. P., Hall A. J., Powell C. A., Downes S., Terrell J. D. Results of case-control study of leukaemia and lymphoma among young people near Sellafield nuclear plant in West Cumbria. BMJ. 1990 Feb 17;300(6722):423–429. doi: 10.1136/bmj.300.6722.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hawkins M. M., Draper G. J., Smith R. A. Cancer among 1,348 offspring of survivors of childhood cancer. Int J Cancer. 1989 Jun 15;43(6):975–978. doi: 10.1002/ijc.2910430604. [DOI] [PubMed] [Google Scholar]
  17. Heisterkamp N., Jenster G., Kioussis D., Pattengale P. K., Groffen J. Human bcr-abl gene has a lethal effect on embryogenesis. Transgenic Res. 1991 Dec;1(1):45–53. doi: 10.1007/BF02512996. [DOI] [PubMed] [Google Scholar]
  18. Huson S. M., Compston D. A., Clark P., Harper P. S. A genetic study of von Recklinghausen neurofibromatosis in south east Wales. I. Prevalence, fitness, mutation rate, and effect of parental transmission on severity. J Med Genet. 1989 Nov;26(11):704–711. doi: 10.1136/jmg.26.11.704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Jones K. P., Wheater A. W. Obstetric outcomes in West Cumberland Hospital: is there a risk from Sellafield? J R Soc Med. 1989 Sep;82(9):524–527. doi: 10.1177/014107688908200906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kinlen L. J. Can paternal preconceptional radiation account for the increase of leukaemia and non-Hodgkin's lymphoma in Seascale? BMJ. 1993 Jun 26;306(6894):1718–1721. doi: 10.1136/bmj.306.6894.1718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kinlen L. J. Epidemiological evidence for an infective basis in childhood leukaemia. Br J Cancer. 1995 Jan;71(1):1–5. doi: 10.1038/bjc.1995.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Little M. P., Charles M. W., Wakeford R. A review of the risks of leukemia in relation to parental pre-conception exposure to radiation. Health Phys. 1995 Mar;68(3):299–310. doi: 10.1097/00004032-199503000-00001. [DOI] [PubMed] [Google Scholar]
  23. Mules E. H., Testa J. R., Thomas G. H., Abbey H., Cohen B. H. Cancer in relatives of leukemic patients with chromosomal rearrangements at rare (heritable) fragile-site locations in their malignant cells. Am J Hum Genet. 1989 Jun;44(6):811–819. [PMC free article] [PubMed] [Google Scholar]
  24. Mulvihill J. J., Myers M. H., Connelly R. R., Byrne J., Austin D. F., Bragg K., Cook J. W., Hassinger D. D., Holmes F. F., Holmes G. F. Cancer in offspring of long-term survivors of childhood and adolescent cancer. Lancet. 1987 Oct 10;2(8563):813–817. doi: 10.1016/s0140-6736(87)91012-9. [DOI] [PubMed] [Google Scholar]
  25. Narod S. A. Radiation, genetics and childhood leukaemia. Eur J Cancer. 1990;26(6):661–664. doi: 10.1016/0277-5379(90)90111-6. [DOI] [PubMed] [Google Scholar]
  26. Neel J. V., Lewis S. E. The comparative radiation genetics of humans and mice. Annu Rev Genet. 1990;24:327–362. doi: 10.1146/annurev.ge.24.120190.001551. [DOI] [PubMed] [Google Scholar]
  27. Neel J. V., Schull W. J., Awa A. A., Satoh C., Kato H., Otake M., Yoshimoto Y. The children of parents exposed to atomic bombs: estimates of the genetic doubling dose of radiation for humans. Am J Hum Genet. 1990 Jun;46(6):1053–1072. [PMC free article] [PubMed] [Google Scholar]
  28. Neel J. V. Update on the genetic effects of ionizing radiation. JAMA. 1991 Aug 7;266(5):698–701. [PubMed] [Google Scholar]
  29. Nomura T. Paternal exposure to radiation and offspring cancer in mice: reanalysis and new evidence. J Radiat Res. 1991 Dec;32 (Suppl 2):64–72. doi: 10.1269/jrr.32.supplement2_64. [DOI] [PubMed] [Google Scholar]
  30. Parker L., Craft A. W., Smith J., Dickinson H., Wakeford R., Binks K., McElvenny D., Scott L., Slovak A. Geographical distribution of preconceptional radiation doses to fathers employed at the Sellafield nuclear installation, West Cumbria. BMJ. 1993 Oct 16;307(6910):966–971. doi: 10.1136/bmj.307.6910.966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Russell W. L., Kelly E. M. Mutation frequencies in male mice and the estimation of genetic hazards of radiation in men. Proc Natl Acad Sci U S A. 1982 Jan;79(2):542–544. doi: 10.1073/pnas.79.2.542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sankaranarayanan K. Genetic effects of ionising radiation in man. Ann ICRP. 1991;22(1):75–94. doi: 10.1016/0146-6453(91)90037-H. [DOI] [PubMed] [Google Scholar]
  33. Sankaranarayanan K. Ionizing radiation and genetic risks. III. Nature of spontaneous and radiation-induced mutations in mammalian in vitro systems and mechanisms of induction of mutations by radiation. Mutat Res. 1991 Jul;258(1):75–97. doi: 10.1016/0165-1110(91)90029-u. [DOI] [PubMed] [Google Scholar]
  34. Stather J. W., Dionian J., Brown J., Fell T. P., Muirhead C. R. The risk of leukemia in Seascale from radiation exposure. Health Phys. 1988 Aug;55(2):471–481. doi: 10.1097/00004032-198808000-00049. [DOI] [PubMed] [Google Scholar]
  35. Stiller C. A., McKinney P. A., Bunch K. J., Bailey C. C., Lewis I. J. Childhood cancer and ethnic group in Britain: a United Kingdom children's Cancer Study Group (UKCCSG) study. Br J Cancer. 1991 Sep;64(3):543–548. doi: 10.1038/bjc.1991.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sutherland G. R., Simmers R. N. No statistical association between common fragile sites and nonrandom chromosome breakpoints in cancer cells. Cancer Genet Cytogenet. 1988 Mar;31(1):9–15. doi: 10.1016/0165-4608(88)90004-0. [DOI] [PubMed] [Google Scholar]
  37. Weinberg R. A. Tumor suppressor genes. Science. 1991 Nov 22;254(5035):1138–1146. doi: 10.1126/science.1659741. [DOI] [PubMed] [Google Scholar]

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