Abstract
Radiation-related risks of cancer can be transported from one population to another population at risk, for the purpose of calculating lifetime risks from radiation exposure. Transfer via excess relative risks (ERR) or excess absolute risks (EAR) or a mixture of both (i.e., from the life span study (LSS) of Japanese atomic bomb survivors) has been done in the past based on qualitative weighting. Consequently, the values of the weights applied and the method of application of the weights (i.e., as additive or geometric weighted means) have varied both between reports produced at different times by the same regulatory body and also between reports produced at similar times by different regulatory bodies. Since the gender and age patterns are often markedly different between EAR and ERR models, it is useful to have an evidence-based method for determining the relative goodness of fit of such models to the data. This paper identifies a method, using Akaike model weights, which could aid expert judgment and be applied to help to achieve consistency of approach and quantitative evidence-based results in future health risk assessments. The results of applying this method to recent LSS cancer incidence models are that the relative EAR weighting by cancer solid cancer site, on a scale of 0–1, is zero for breast and colon, 0.02 for all solid, 0.03 for lung, 0.08 for liver, 0.15 for thyroid, 0.18 for bladder and 0.93 for stomach. The EAR weighting for female breast cancer increases from 0 to 0.3, if a generally observed change in the trend between female age-specific breast cancer incidence rates and attained age, associated with menopause, is accounted for in the EAR model. Application of this method to preferred models from a study of multi-model inference from many models fitted to the LSS leukemia mortality data, results in an EAR weighting of 0. From these results it can be seen that lifetime risk transfer is most highly weighted by EAR only for stomach cancer. However, the generalization and interpretation of radiation effect estimates based on the LSS cancer data, when projected to other populations, are particularly uncertain if considerable differences exist between site-specific baseline rates in the LSS and the other populations of interest. Definitive conclusions, regarding the appropriate method for transporting cancer risks, are limited by a lack of knowledge in several areas including unknown factors and uncertainties in biological mechanisms and genetic and environmental risk factors for carcinogenesis; uncertainties in radiation dosimetry; and insufficient statistical power and/or incomplete follow-up in data from radio-epidemiological studies.
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Acknowledgments
Dr. Walsh would like to thank Prof. Richard Wakeford (University of Manchester, U.K.) for drawing her attention to the current situation regarding the subjective nature of the weighting of ERR and EAR models for the calculation of lifetime risks of cancer from radiation exposure. The authors would also like to thank Prof. Donald A. Pierce, Dr. Elke A. Nekolla, Dr Charles Land, Dr. Roy Shore, Dr Michaela Kreuzer, Dr. Jan C. Kaiser and Dr. Peter Jacob for useful discussions. They would also like to thank two anonymous reviewers for their careful considerations and for providing many interesting points for the discussion section. This work was partly supported by the seventh framework program of the European Union, FP-7-EU-ANDANTE (Multidisciplinary evaluation of the cancer risk from neutrons relative to photons using stem cells and the analysis of second malignant neoplasms following paediatric radiation therapy). This work makes use of the data obtained from the Radiation Effects Research Foundation (RERF) in Hiroshima, Japan. RERF is a private foundation funded equally by the Japanese Ministry of Health and Welfare and the US Department of Energy through the US National Academy of Sciences. The conclusions in this work are those of the authors and do not necessarily reflect the scientific judgement of RERF or its funding agencies.
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Walsh, L., Schneider, U. A method for determining weights for excess relative risk and excess absolute risk when applied in the calculation of lifetime risk of cancer from radiation exposure. Radiat Environ Biophys 52, 135–145 (2013). https://doi.org/10.1007/s00411-012-0441-x
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DOI: https://doi.org/10.1007/s00411-012-0441-x