Systematic Review and Meta-Analysis of Circulatory Disease from Exposure to Low-Level Ionizing Radiation and Estimates of Potential Population Mortality Risks
Mark P. Little,1 Tamara V. Azizova,2 Dimitry Bazyka,3 Simon D. Bouffler,4 Elisabeth Cardis,5 Sergey Chekin,6 Vadim V. Chumak,3 Francis A. Cucinotta,7 Florent de Vathaire,8 Per Hall,9 John D. Harrison,4 Guido Hildebrandt,10,11 Victor Ivanov,6 Valeriy V. Kashcheev,6 Sergiy V. Klymenko,3 Michaela Kreuzer,12 Olivier Laurent,13 Kotaro Ozasa,14 Thierry Schneider,15 Soile Tapio,16 Andrew M. Taylor,17 Ioanna Tzoulaki,18 Wendy L. Vandoolaeghe,18 Richard Wakeford,19 Lydia B. Zablotska,20 Wei Zhang,4 and Steven E. Lipshultz21
1Radiation Epidemiology Branch, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland, USA; 2Southern Urals Biophysics Institute, Ozyorsk, Russia; 3Research Center for Radiation Medicine, Kyiv, Ukraine; 4Health Protection Agency, Centre for Radiation, Chemical and Environmental Hazards, Chilton, United Kingdom; 5Center for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; 6Medical Radiological Research Center of Russian Academy of Medical Sciences, Obninsk, Russia; 7NASA Johnson Space Center, Space Radiation Program, Houston, Texas, USA; 8Radiation Epidemiology Group, INSERM (Institut National de la Santé et de la Recherche Médicale) Unité U1018, Institut Gustave Roussy, Villejuif, France; 9Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; 10Department of Radiotherapy and Radiation Oncology, University of Leipzig, Leipzig, Germany; 11Department of Radiotherapy and Radiation Oncology, University of Rostock, Rostock, Germany; 12Federal Office for Radiation Protection, Department of Radiation Protection and Health, Oberschleissheim, Germany; 13Laboratoire d’Epidémiologie, Institut de Radioprotection et de Sûreté Nucleaire, Fontenay-aux-Roses, France; 14Department of Epidemiology, Radiation Effects Research Foundation, Hiroshima City, Japan; 15CEPN (Nuclear Evaluation Protection Center), Fontenay-aux-Roses, France; 16Helmholtz Zentrum München, German Research Centre for Environmental Health, Institute of Radiation Biology (ISB), Radiation Proteomics, Oberschleissheim, Germany; 17University College London Institute of Cardiovascular Sciences & Great Ormond Street Hospital for Children, London, United Kingdom; 18Department of Epidemiology and Biostatistics, Imperial College Faculty of Medicine, London, United Kingdom; 19Dalton Nuclear Institute, University of Manchester, Manchester, United Kingdom; 20Department of Epidemiology and Biostatistics, University of California San Francisco School of Medicine, San Francisco, California, USA; 21Department of Pediatrics, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida, USA
Background: Although high doses of ionizing radiation have long been linked to circulatory disease, evidence for an association at lower exposures remains controversial. However, recent analyses suggest excess relative risks at occupational exposure levels.
Objectives: We performed a systematic review and meta-analysis to summarize information on circulatory disease risks associated with moderate- and low-level whole-body ionizing radiation exposures.
Methods: We conducted PubMed/ISI Thomson searches of peer-reviewed papers published since 1990 using the terms “radiation” AND “heart” AND “disease,” OR “radiation” AND “stroke,” OR “radiation” AND “circulatory” AND “disease.” Radiation exposures had to be whole-body, with a cumulative mean dose of < 0.5 Sv, or at a low dose rate (< 10 mSv/day). We estimated population risks of circulatory disease from low-level radiation exposure using excess relative risk estimates from this meta-analysis and current mortality rates for nine major developed countries.
Results: Estimated excess population risks for all circulatory diseases combined ranged from 2.5%/Sv [95% confidence interval (CI): 0.8, 4.2] for France to 8.5%/Sv (95% CI: 4.0, 13.0) for Russia.
Conclusions: Our review supports an association between circulatory disease mortality and low and moderate doses of ionizing radiation. Our analysis was limited by heterogeneity among studies (particularly for noncardiac end points), the possibility of uncontrolled confounding in some occupational groups by lifestyle factors, and higher dose groups (> 0.5 Sv) generally driving the observed trends. If confirmed, our findings suggest that overall radiation-related mortality is about twice that currently estimated based on estimates for cancer end points alone (which range from 4.2% to 5.6%/Sv for these populations).
Key words: cancer, circulatory disease, heart disease, radiation, stroke.
Environ Health Perspect 120:1503–1511 (2012). http://dx.doi.org/10.1289/ehp.1204982 [Online 22 June 2012]
Address correspondence to M.P. Little, Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza South, 6120 Executive Blvd. MSC 7238, Rockville, MD 20852-7238 USA. Telephone: (301) 402-9138 (office); (301) 875-3413 (mobile). Fax: (301) 402-0207. E-mail: firstname.lastname@example.org
Supplemental Material is available online (http://dx.doi.org/10.1289/ehp.1204982).
We are grateful for the detailed and helpful comments of K. Mabuchi, A. Berrington de González, M. Cook, B. Graubard, B. Bridges, D. Stram, J. Hendry, S. Schultz-Hector, F. Stewart, B. Jones, the two referees, and an editor.
This work was funded partially by the European Commission (EC) under contract FP6-036465 [NOn-Targeted Effects of ionising radiation (NOTE) integrated project]. This research was also supported by the Intramural Research Program of the National Institutes of Health (NIH) and the National Cancer Institute. This report makes use of data obtained from the Radiation Effects Research Foundation (RERF), Hiroshima and Nagasaki, Japan. RERF is a private, nonprofit foundation funded by the Japanese Ministry of Health, Labour and Welfare and the U.S. Department of Energy, the latter through the National Academy of Sciences.
Neither the EC nor the NIH had any role in study design and the collection, analysis, and interpretation of data or the writing of the article and the decision to submit it for publication; all researchers are independent of all funders and sponsors. The conclusions of the report are those of the authors and do not necessarily reflect the scientific judgment of RERF or its funding agencies.
The authors declare they have no actual or potential competing financial interests.
Received 16 January 2012; Accepted 22 June 2012; Online 22 June 2012.
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