Leukaemia and myeloid malignancy among people exposed to low doses (<100 mSv) of ionising radiation during childhood: a pooled analysis of nine historical cohort studies
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Background Substantial evidence links exposure to moderate or high doses of ionising radiation, particularly in childhood, with increased risk of leukaemia. The association of leukaemia with exposure to low-dose (<100 mSv) radiation is less certain, although this is the dose range most relevant to the general population. We aimed to estimate the risk of leukaemia associated with low-dose radiation exposure in childhood (age <21 years).Methods In this analysis of historical cohort studies, we pooled eligible cohorts reported up to June 30, 2014. We evaluated leukaemia and myeloid malignancy outcomes in these cohorts with the relevant International Classification of Diseases and International Classification of Diseases for Oncology definitions. The cohorts included had not been treated for malignant disease, had reported at least five cases of the relevant haematopoietic neoplasms, and estimated individual active bone marrow (ABM) doses. We restricted analysis to individuals who were younger than 21 years at first irradiation who had mean cumulative ABM doses of less than 100 mSv. Dose-response models were fitted by use of Poisson regression. The data were received in fully anonymised form by the statistical analyst.Findings We identified nine eligible cohorts from Canada, France, Japan, Sweden, the UK, and the USA, including 262 573 people who had been exposed to less than 100 mSv enrolled between June 4, 1915, and Dec 31, 2004. Mean follow-up was 19·63 years (SD 17·75) and mean cumulative ABM dose was 19·6 mSv (SD 22·7). 154 myeloid malignancies were identified (which included 79 acute myeloid leukaemias, eight myelodysplastic syndromes, and 36 chronic myeloid leukaemias, in addition to other unspecified myeloid malignancies) and 40 acute lymphoblastic leukaemias, with 221 leukaemias (including otherwise unclassified leukaemias but excluding chronic lymphocytic leukaemia) identified overall. The fitted relative risks at 100 mSv were 3·09 (95% CI 1·41-5·92; p trend=0·008) for acute myeloid leukaemia and myelodysplastic syndromes combined, 2·56 (1·09-5·06; p trend=0·033) for acute myeloid leukaemia, and 5·66 (1·35-19·71; p trend=0·023) for acute lymphoblastic leukaemia. There was no clear dose-response for chronic myeloid leukaemia, which had a relative risk at 100 mSv of 0·36 (0·00-2·36; p trend=0·394). There were few indications of between-cohort heterogeneity or departure from linearity. For acute myeloid leukaemia and myelodysplastic syndromes combined and for acute lymphoblastic leukaemia, the dose-responses remained significant for doses of less than 50 mSv. Excess absolute risks at 100 mSv were in the range of 0·1-0·4 cases or deaths per 10 000 person-years.Interpretation The risks of acute myeloid leukaemia and acute lymphoblastic leukaemia were significantly increased after cumulative doses of ionising radiation of less than 100 mSv in childhood or adolescence, with an excess risk also apparent for cumulative radiation doses of less than 50 mSv for some endpoints. These findings support an increased risk of leukaemia associated with low-dose exposure to radiation and imply that the current system of radiological protection is prudent and not overly protective.Funding National Cancer Institute Intramural Research Program, National Cancer Institute, and US National Institutes for Health.
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Our leukemia risk estimate is compatible with those derived in a recent combined analysis of data on individuals exposed before age 21 and ABM dose <100 mGy (ERR/100 mGy 0.84-4.66, depending on leukemia subtype).
“Indeed, our leukemia risk estimate is compatible with those derived in a recent combined analysis of data on individuals exposed before the age of 21 years and ABM dose <100 mGy (ERR/100 mGy 0.84–4.66, depending on leukemia subtype)38.”
From Risk of hematological malignancies from CT radiation exposure in children, adolescents and young adults (2023) · cites this paper as [38]
The Results report fitted relative risks of 1.84 for leukaemia excluding chronic lymphocytic leukaemia and 5.66 for acute lymphoblastic leukaemia at 100 mSv; subtracting 1 gives the cited excess-relative-risk endpoints of 0.84 and 4.66. The Methods (Procedures, Radiation dosimetry) say doses were expressed as equivalent doses in mSv, not absorbed doses in mGy, so the cited dose unit is not established by this paper. (LLM, conf=0.84)
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The Evidence for Excess Risk of Cancer and Non-Cancer Disease at Low Doses and Dose Rates
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Therapy-Related Myeloid Neoplasms in 109 Patients Following Radiation Monotherapy
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Lifetime attributable risk of cancer incidence and mortality in routine digital radiology procedures
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Birth characteristics and childhood leukemia in Switzerland: a register-based case–control study
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Integration of multi-omics and benchmark dose modeling to support adverse outcome pathways
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Minimum latency effects for cancer associated with exposures to radiation or other carcinogens
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Preleukemic Fusion Genes Induced via Ionizing Radiation
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A generalisation of the method of regression calibration
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- Authors
- Little, M. P., Wakeford, R., Borrego, D., French, B., Zablotska, L. B., Adams, M. J., Allodji, R., de Vathaire, F., Lee, C., Brenner, A. V., Miller, J. S., Campbell, D., Pearce, M. S., Doody, M. M., Holmberg, E., Lundell, M., Sadetzki, S., Linet, M. S., & Berrington de González, A.
- Affiliations
- National Institutes of Health (US)
- University of Manchester (GB)
- National Cancer Institute (US)
- Radiation Effects Research Foundation (JP)
- University of California, San Francisco (US)
- University of Rochester Medicine (US)
- Inserm (FR)
- Information Management Services (US)
- National Institute for Health and Care Research (GB)
- Sahlgrenska University Hospital (SE)
- Karolinska University Hospital (SE)
- Tel Aviv University (IL)
- Corresponding author
- Little, Mark P
- ORCID
- Venue
- The Lancet Haematology
- Publisher
- Elsevier BV
- Published
- 2018-08
- Volume
- 5
- Issue
- 8
- Pages
- e346-e358
- ISSN
- 2352-3026 (ISSN-L)
- PMC
- PMC6130888
- OpenAlex
- W2883741998
- Cited by
- 152
- References
- 41
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 23 · 2023: 17 · 2022: 23 · 2021: 30 · 2020: 21 · 2019: 13 · 2018: 3
- FWCI
- 11.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The Lancet Haematology (acceptedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity) (cc-by-nc-nd)
- Funders
- National Academy of Sciences
- Foundation for the National Institutes of Health (R01CA197422, R03CA188614)
- Division of Cancer Epidemiology and Genetics, National Cancer Institute
- Ministry of Health, Labour and Welfare
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiation Dose and Imaging
- Health Sciences › Health Professions › Radiological and Ultrasound Technology › Radioactivity and Radon Measurements
- Keywords
- pediatric radiation exposure, low-dose radiation, leukemia, myeloid neoplasms, acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia, myelodysplastic syndrome, dose-response relationship, radiation-induced cancer risk, historical cohort study, pooled analysis
- MeSH terms
- Adult, Aged, Child, Female, Humans, Leukemia, Male, Middle Aged, Neoplasms, Radiation-Induced, Radiation Dosage, Risk, Cohort Studies, Bone Marrow Neoplasms, Young Adult
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