Abstract
Breast cancer risk from radiation exposure has been analyzed in the cohort of Japanese a-bomb survivors using empirical models and mechanistic two-step clonal expansion (TSCE) models with incidence data from 1958 to 1998. TSCE models rely on a phenomenological representation of cell transition processes on the path to cancer. They describe the data as good as empirical models and this fact has been exploited for risk assessment. Adequate models of both types have been selected with a statistical protocol based on parsimonious parameter deployment and their risk estimates have been combined using multi-model inference techniques. TSCE models relate the radiation risk to cell processes which are controlled by age-increasing rates of initiating mutations and by changes in hormone levels due to menopause. For exposure at young age, they predict an enhanced excess relative risk (ERR) whereas the preferred empirical model shows no dependence on age at exposure. At attained age 70, the multi-model median of the ERR at 1 Gy decreases moderately from 1.2 Gy−1 (90% CI 0.72; 2.1) for exposure at age 25 to a 30% lower value for exposure at age 55. For cohort strata with few cases, where model predictions diverge, uncertainty intervals from multi-model inference are enhanced by up to a factor of 1.6 compared to the preferred empirical model. Multi-model inference provides a joint risk estimate from several plausible models rather than relying on a single model of choice. It produces more reliable point estimates and improves the characterization of uncertainties. The method is recommended for risk assessment in practical radiation protection.
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Notes
William of Occam’s (* 1287 near London, \(\dag\) 1347 in Munich) principle of parsimony or Occam’s razor is often phrased as pluralitas non est ponenda sine necessitate (plurality should not be posited without necessity).
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Acknowledgments
This report makes use of data obtained from the Radiation Effects Research Foundation (RERF) in Hiroshima and Nagasaki, Japan. RERF is a private, non-profit foundation funded by the Japanese Ministry of Health, Labour and Welfare (MHLW) and the US Department of Energy (DOE), the latter in part through the National Academy of Sciences. The data include information obtained from the Hiroshima City, Hiroshima Prefecture, Nagasaki City, and Nagasaki Prefecture Tumor Registries and the Hiroshima and Nagasaki Tissue Registries. The conclusions in this report are those of the authors and do not necessarily reflect the scientific judgment of RERF or its funding agencies. The work has been supported by the German Federal Ministry of Environment, Nature Protection and Reactor Safety under contract number StSch4451. We would like to thank Linda Walsh for sharing ideas on multi-model inference, Markus Eidemüller for his computer code on LHS sampling and Helmut Schöllnberger for discussions on mechanistic models.
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Kaiser, J.C., Jacob, P., Meckbach, R. et al. Breast cancer risk in atomic bomb survivors from multi-model inference with incidence data 1958–1998. Radiat Environ Biophys 51, 1–14 (2012). https://doi.org/10.1007/s00411-011-0387-4
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DOI: https://doi.org/10.1007/s00411-011-0387-4