Dose–responses from multi-model inference for the non-cancer disease mortality of atomic bomb survivors

Abstract

The non-cancer mortality data for cerebrovascular disease (CVD) and cardiovascular diseases from Report 13 on the atomic bomb survivors published by the Radiation Effects Research Foundation were analysed to investigate the dose–response for the influence of radiation on these detrimental health effects. Various parametric and categorical models (such as linear-no-threshold (LNT) and a number of threshold and step models) were analysed with a statistical selection protocol that rated the model description of the data. Instead of applying the usual approach of identifying one preferred model for each data set, a set of plausible models was applied, and a sub-set of non-nested models was identified that all fitted the data about equally well. Subsequently, this sub-set of non-nested models was used to perform multi-model inference (MMI), an innovative method of mathematically combining different models to allow risk estimates to be based on several plausible dose–response models rather than just relying on a single model of choice. This procedure thereby produces more reliable risk estimates based on a more comprehensive appraisal of model uncertainties. For CVD, MMI yielded a weak dose–response (with a risk estimate of about one-third of the LNT model) below a step at 0.6 Gy and a stronger dose–response at higher doses. The calculated risk estimates are consistent with zero risk below this threshold-dose. For mortalities related to cardiovascular diseases, an LNT-type dose–response was found with risk estimates consistent with zero risk below 2.2 Gy based on 90% confidence intervals. The MMI approach described here resolves a dilemma in practical radiation protection when one is forced to select between models with profoundly different dose–responses for risk estimates.Electronic supplementary materialThe online version of this article (doi:10.1007/s00411-012-0410-4) contains supplementary material, which is available to authorized users.

Circulatory disease mortality in the Massachusetts tuberculosis fluoroscopy cohort study

“…As such this does not represent a true noeffect dose threshold. Schollnberger et al [52], analyzing somewhat older Japanese atomic bomb survivor data, concluded that for CeVD and cardiovascular disease, risk estimates are compatible with no risk below threshold doses of 0.62 and 2.19 Gy respectively. However, this analysis is controversial [53].…”

Transcriptomic profiling suggests a role for IGFBP5 in premature senescence of endothelial cells after chronic low dose rate irradiation

“…Recently, a new method of analysis by fi tting multiple dose-response models on LSS data has been proposed by Sch ö llnberger and co-workers to produce more reliable risk estimates. Th eir fi ndings support a linear nonthreshold type of response for mortalities related to CVD in the LSS cohort, with risk estimates consistent with zero risk below 2.2 Gy based on 90% confi dence intervals (Schollnberger et al 2012). Regarding cardiovascular risks related to protracted exposures, major sources of information are occupational cohorts and cohorts living in areas with high level background radiation (Hendry et al 2009).…”

“…Major sources of information are the Life Span Study (LSS) cohort and the Adult Health Study (AHS) cohort from Japanese atomic bomb survivors, which revealed an excess risk of stroke and heart disease following exposure to lower doses of ionizing radiation (Shimizu et al 2010, Schollnberger et al 2012. However, there is still considerable uncertainty about the dose-risk relationship, in particular for low ( Ͻ 0.5 Gy) and moderate (0.5 -5 Gy) doses (Shimizu et al 2010).…”

Low dose radiation and circulatory diseases: a brief narrative review

“…At high radiation doses (>5 Gy), a variety of other well established effects are observed; in particular, damage to the structures of the heart and to the coronary, carotid, and other large arteries [10]. Several recent reviews have suggested an excess radiation-induced risk at occupational and environmental dose levels (<0.5 Gy 1 ) [2,[11][12][13][14][15], although the presence and magnitude of low-dose risk is still unclear, with some advocating for the use of a threshold [16,17]. The results of a recent meta-analysis suggest that if the risks were applied to various current populations that overall radiation-related mortality would be about twice that currently estimated based on estimates for cancer endpoints alone [13].…”