Abstract
Background
Many high-dose groups demonstrate increased leukaemia risks, with risk greatest following childhood exposure; risks at low/moderate doses are less clear.
Methods
We conducted a pooled analysis of the major radiation-associated leukaemias (acute myeloid leukaemia (AML) with/without the inclusion of myelodysplastic syndrome (MDS), chronic myeloid leukaemia (CML), acute lymphoblastic leukaemia (ALL)) in ten childhood-exposed groups, including Japanese atomic bomb survivors, four therapeutically irradiated and five diagnostically exposed cohorts, a mixture of incidence and mortality data. Relative/absolute risk Poisson regression models were fitted.
Results
Of 365 cases/deaths of leukaemias excluding chronic lymphocytic leukaemia, there were 272 AML/CML/ALL among 310,905 persons (7,641,362 person-years), with mean active bone marrow (ABM) dose of 0.11 Gy (range 0–5.95). We estimated significant (P < 0.005) linear excess relative risks/Gy (ERR/Gy) for: AML (n = 140) = 1.48 (95% CI 0.59–2.85), CML (n = 61) = 1.77 (95% CI 0.38–4.50), and ALL (n = 71) = 6.65 (95% CI 2.79–14.83). There is upward curvature in the dose response for ALL and AML over the full dose range, although at lower doses (<0.5 Gy) curvature for ALL is downwards.
Discussion
We found increased ERR/Gy for all major types of radiation-associated leukaemia after childhood exposure to ABM doses that were predominantly (for 99%) <1 Gy, and consistent with our prior analysis focusing on <100 mGy.
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Data availability
The data are available from the first author upon request.
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Funding
This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics. The Radiation Effects Research Foundation (RERF), Hiroshima and Nagasaki, Japan is a public interest foundation funded by the Japanese Ministry of Health, Labour and Welfare (MHLW) and the US Department of Energy (DOE). The research was also funded in part through DOE award DE-HS0000031 to the National Academy of Sciences. Dr Zablotska’s work was supported by the National Cancer Institute of the National Institutes of Health under the R01CA197422 award. This publication was supported by RERF Research Protocol A1-16. The views of the authors do not necessarily reflect those of the two governments.
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All authors contributed to the study’s conception and design. Material preparation, data collection and analysis were performed by Mark Little with assistance from Jeremy Miller and David Campbell. The first draft of the manuscript was written by Mark Little and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Richard Wakeford is a member of the Technical Working Party of the UK Compensation Scheme for Radiation-Linked Diseases (http://www.csrld.org.uk), for which he is paid a consultancy fee. The Technical Working Party is unaware of the contents of this article, which are entirely independent of any views held by other members of the Technical Working Party. The remaining authors declare no competing interests.
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Little, M.P., Wakeford, R., Zablotska, L.B. et al. Radiation exposure and leukaemia risk among cohorts of persons exposed to low and moderate doses of external ionising radiation in childhood. Br J Cancer 129, 1152–1165 (2023). https://doi.org/10.1038/s41416-023-02387-8
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DOI: https://doi.org/10.1038/s41416-023-02387-8