Radiation and the Risk of Chronic Lymphocytic and Other Leukemias among Chornobyl Cleanup Workers

Lydia B. Zablotska,¹ Dimitry Bazyka,² Jay H. Lubin,³ Nataliya Gudzenko,² Mark P. Little,³ Maureen Hatch,³ Stuart Finch,⁴ Irina Dyagil,² Robert F. Reiss,^5,6 Vadim V. Chumak,² Andre Bouville,³ Vladimir Drozdovitch,³ Victor P. Kryuchkov,⁷ Ivan Golovanov,⁷ Elena Bakhanova,² Nataliya Babkina,² Tatiana Lubarets,² Volodymyr Bebeshko,² Anatoly Romanenko,² and Kiyohiko Mabuchi³

¹Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco, San Francisco, California, USA; ²National Research Center for Radiation Medicine, Kyiv, Ukraine; ³Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA; ⁴Robert Wood Johnson Medical School, Camden, New Jersey, USA; ⁵Department of Pathology and Cell Biology, and ⁶Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, USA; ⁷Burnasyan Federal Medical Biophysical Centre, Moscow, Russia


Abstract

Background: Risks of most types of leukemia from exposure to acute high doses of ionizing radiation are well known, but risks associated with protracted exposures, as well as associations between radiation and chronic lymphocytic leukemia (CLL), are not clear.


Objectives: We estimated relative risks of CLL and non-CLL from protracted exposures to low-dose ionizing radiation.


Methods: A nested case–control study was conducted in a cohort of 110,645 Ukrainian cleanup workers of the 1986 Chornobyl nuclear power plant accident. Cases of incident leukemia diagnosed in 1986–2006 were confirmed by a panel of expert hematologists/hematopathologists. Controls were matched to cases on place of residence and year of birth. We estimated individual bone marrow radiation doses by the Realistic Analytical Dose Reconstruction with Uncertainty Estimation (RADRUE) method. We then used a conditional logistic regression model to estimate excess relative risk of leukemia per gray (ERR/Gy) of radiation dose.


Results: We found a significant linear dose response for all leukemia [137 cases, ERR/Gy = 1.26 (95% CI: 0.03, 3.58]. There were nonsignificant positive dose responses for both CLL and non-CLL (ERR/Gy = 0.76 and 1.87, respectively). In our primary analysis excluding 20 cases with direct in-person interviews < 2 years from start of chemotherapy with an anomalous finding of ERR/Gy = –0.47 (95% CI: < –0.47, 1.02), the ERR/Gy for the remaining 117 cases was 2.38 (95% CI: 0.49, 5.87). For CLL, the ERR/Gy was 2.58 (95% CI: 0.02, 8.43), and for non-CLL, ERR/Gy was 2.21 (95% CI: 0.05, 7.61). Altogether, 16% of leukemia cases (18% of CLL, 15% of non-CLL) were attributed to radiation exposure.


Conclusions: Exposure to low doses and to low dose-rates of radiation from post-Chornobyl cleanup work was associated with a significant increase in risk of leukemia, which was statistically consistent with estimates for the Japanese atomic bomb survivors. Based on the primary analysis, we conclude that CLL and non-CLL are both radiosensitive.


Key words: Chernobyl nuclear accident, Chornobyl, Ukraine, chronic lymphocytic leukemia, leukemia, matched case–control study, radiation, radiation dose–response relationship, radiation-induced leukemia. 


Environ Health Perspect 121:59–65 (2013). http://dx.doi.org/10.1289/ehp.1204996 [Online 8 November 2012]


Address correspondence to L.B. Zablotska, Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco, 3333 California St., Suite 280, San Francisco, CA 94118 USA. Telephone: (415) 476-4673. Fax: (415) 563-4602. E-mail: lydia.zablotska@ucsf.edu


Supplemental Material is available online (http://dx.doi.org/10.1289/ehp.1204996).


We thank the staff of the National Research Center for Radiation Medicine (Kyiv, Ukraine), and especially study epidemiologists and interviewers, for their dedication and commitment to the success of the study. We express our deep appreciation of the work of the members of the International Hematology Panel: B.J. Bain, L. Peterson, P. McPhedran, S.N. Gaidukova, and D.F. Gluzman; likewise, the members of the Leukemia Advisory Group for their wise counsel: F.L. Wong, H. Checkoway, K. Eckerman, B. Chabner, and B. Cheson. We acknowledge G.R. Howe, one of the original principal investigators of the study, for his contributions to setting up this study and for his foresight in recognizing the future need for accurate cancer diagnosis information and his significant efforts to computerize the Ukrainian Cancer Registry. We also acknowledge the late E. Ron, who played a major role in the conduct of this study. We are greatly saddened by her death, and her wisdom and guidance will be greatly missed. We thank D.L. Preston for his review of the draft of the manuscript and helpful discussions.


Funding for this study was provided by the National Cancer Institute (NCI grant CA132918 and contract NO1-CP-21178 to L.B.Z. and the Intramural Research Program of the Division of Cancer Epidemiology and Genetics to J.H.L., M.P.L., M.H., A.B., V.D., and K.M.). Radiation dose reconstruction was partially supported by an intra-agency agreement between the National Institute of Allergy and Infectious Diseases (NIAID) and the NCI (NIAID agreement Y2-Al-5077 and NCI agreement Y3-CO-5117). At earlier stages of the study, the U.S. Department of Energy (contract HHSN 261 2004 55796C), the Nuclear Regulatory Commission, and the French Institute for Radiological Protection and Nuclear Safety contributed additional funding.


The authors declare they have no actual or potential competing financial interests.


Received 21 January 2012; Accepted 24 October 2012; Online 8 November 2012.