Abstract
While there is a well-established link between ionizing radiation and cancer, there are uncertainties with effects following low doses delivered at low dose rates. To address these gaps, the ongoing Million Person Study of Radiation Workers and Veterans (MPS) is investigating the likelihood of a variety of cancer and non-cancer effects following chronic exposure to low dose-rate ionizing radiation. One challenge is and will be combining and harmonizing diverse cohorts with widely different measures of socio-economic status, birth cohorts, dose distributions and sex ratios. Herein, we have evaluated non-cancer mortality in three cohorts for which dose reconstructions have been completed: Rocketdyne (Atomics International, California, 1948-2008), Mound (Dayton, Ohio, 1944-2009) and nuclear weapons test participants (Atomic Veterans, 1945-2012). These three cohorts represent a small fraction of the overall MPS but provide valuable insight into methods of combining and harmonizing data from multiple diverse cohorts that can later be considered for all MPS cohorts. Heart disease mortality, including both underlying and contributing causes of death, was chosen for illustrating the statistical approaches. In all three cohorts, radiation dose estimates were distributed very differently by different measures of socio-economic status. Further, the effect of birth cohort was significantly different for heart disease mortality in all three cohorts, with all studies showing that later birth cohorts have lower rates of heart disease mortality than the earlier. The goal of this paper is not to quantify radiation effects based on these combined cohorts and it would be inappropriate to do so. Rather these cohorts are used to illustrate approaches for combining multiple data sets that incorporate the full set of individual confounder and cofactor information available from each cohort, though widely different. We identified five different methods to combine the results of these three datasets: the simple pooled analysis (PA), PA including study interactions, traditional stratified analysis, and both fixed and random effects meta-analysis. We describe the similarities and differences between the combined results using these approaches.
| Original language | English |
|---|---|
| Article number | 021502 |
| Journal | Journal of Radiological Protection |
| Volume | 45 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jun 1 2025 |
Funding
The workers at Mound and Rocketdyne and the atomic veterans are components of the Million Person Study supported in part by a research Grant from the U.S. Department of Energy (DOE) (Grant No. DE-SC0008944) awarded to the National Council on Radiation Protection and Measurements, which included interagency support from the U.S. Nuclear Regulatory Commission (NRC), the U.S. Environmental Protection Agency and the National Aeronautics and Space Administration (NASA)); and a Discovery Grant from the Vanderbilt-lngram Cancer Center (Center no. 404-357-9682). The study of atomic veterans also was supported by a Grant from the National Cancer Institute (Grant No. U01 CA137026). We acknowledge Dr Paul Blake, Chief, Nuclear Test Personnel Review, Defense Threat Reduction Agency, U.S. Department of Defense and his staff for their technical support of the atomic veterans project, and Hanson Gaugler at L-3 Services for his critical contributions to our accessing and interpreting the comprehensive data sources necessary for study conduct. Similarly, Han Kang and Tim Bullman, Environmental Epidemiology Service, U.S. Department of Veterans Affairs, were instrumental in providing support and assistance throughout the conduct of the Eight Series Study of atomic veterans. We also are indebted to the DOE (Nimi Rao), the NRC (Doris Lewis), Oak Ridge Associated Universities (Derek A Hagemeyer), Landauer, Inc. (Craig Yoder, PhD), the U.S. Army Dosimetry Center (William S Harris, Jr., CHP), the U.S. Air Force Radiation Dosimetry Laboratory (Ms. Linda Wilson), and the Naval Dosimetry Center (CDR Anthony Williams and Lt Selena Hayes) for facilitating linkages with their respective dosimetry files. The results presented herein represent the conclusions and opinions solely of the authors. Its publication does not imply endorsement by the National Council on Radiation Protection and Measurements, Vanderbilt University, Harvard University, Columbia University, Oak Ridge National Laboratory or any of the acknowledged agencies. For unrelated work, Andrew Einstein reports receiving a speaker’s fee from Ionetix, consulting for W L Gore & Associates and Artrya, authorship fees from Wolters Kluwer Healthcare—UpToDate, and serving on a scientific advisory board for Canon Medical Systems USA; his institution has Grants/Grants pending from Attralus, BridgeBio, Canon Medical Systems USA, GE HealthCare, Intellia Therapeutics, Ionis Pharmaceuticals, Neovasc, Pfizer, Roche Medical Systems, and W L Gore & Associates.
Keywords
- meta-analysis
- million person study
- pooled analysis
- radiation epidemiology
- statistical approaches to harmonization