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Effect of follow-up period on minimal-significant dose in the atomic-bomb survivor studies.

ABSTRACT: It was recently suggested that earlier reports on solid-cancer mortality and incidence in the Life Span Study of atomic-bomb survivors contain still-useful information about low-dose risk that should not be ignored, because longer follow-up may lead to attenuated estimates of low-dose risk due to longer time since exposure. Here it is demonstrated, through the use of all follow-up data and risk models stratified on period of follow-up (as opposed to sub-setting the data by follow-up period), that the appearance of risk attenuation over time may be the result of less-precise risk estimation-in particular, imprecise estimation of effect-modification parameters-in the earlier periods. Longer follow-up, in addition to allowing more-precise estimation of risk due to larger numbers of radiation-related cases, provides more-precise adjustment for background mortality or incidence and more-accurate assessment of risk modification by age at exposure and attained age. It is concluded that the latest follow-up data are most appropriate for inferring low-dose risk. Furthermore, if researchers are interested in effects of time since exposure, the most-recent follow-up data should be considered rather than the results of earlier reports.

SUBMITTER: Cologne J

PROVIDER: S-EPMC5816089 | biostudies-other | 2018 Mar

REPOSITORIES: biostudies-other

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Effect of follow-up period on minimal-significant dose in the atomic-bomb survivor studies.

Cologne John J Preston Dale L DL Grant Eric J EJ Cullings Harry M HM Ozasa Kotaro K

Radiation and environmental biophysics 20171121 1

It was recently suggested that earlier reports on solid-cancer mortality and incidence in the Life Span Study of atomic-bomb survivors contain still-useful information about low-dose risk that should not be ignored, because longer follow-up may lead to attenuated estimates of low-dose risk due to longer time since exposure. Here it is demonstrated, through the use of all follow-up data and risk models stratified on period of follow-up (as opposed to sub-setting the data by follow-up period), tha ...[more]

PMID: 29164324

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Project description:Dosimetric measurement error is known to potentially bias the magnitude of the dose response, and can also affect the shape of dose response. In this report, generalized relative and absolute rate models are fitted to the latest Japanese atomic bomb survivor solid cancer, leukemia and circulatory disease mortality data (followed from 1950 through 2003), with the latest (DS02R1) dosimetry, using Bayesian techniques to adjust for errors in dose estimates and assessing other model uncertainties. Linear-quadratic models are fitted and used to assess lifetime mortality risks for contemporary UK, USA, French, Russian, Japanese and Chinese populations. For a test dose of 0.1 Gy absorbed dose weighted by neutron relative biological effectiveness, solid cancer, leukemia and circulatory disease mortality risks for a UK population using a generalized linear-quadratic relative rate model were estimated to be 3.88% Gy-1 [95% Bayesian credible interval (BCI): 1.17, 6.97], 0.35% Gy-1 (95% BCI: -0.03, 0.78) and 2.24% Gy-1 (95% BCI: -0.17, 13.76), respectively. Using a generalized absolute rate linear-quadratic model at 0.1 Gy, the lifetime risks for these three end points were estimated to be 3.56% Gy-1 (95% BCI: 0.54, 6.78), 0.41% Gy-1 (95% BCI: 0.01, 0.86) and 1.56% Gy-1 (95% BCI: -1.10, 7.21), respectively. There was substantial evidence of curvature for solid cancer (in particular, the group of solid cancers excluding lung, breast and stomach cancers) and leukemia, so that for solid cancer and leukemia, estimates of excess risk per unit dose were nearly doubled by increasing the dose from 0.01 to 1.0 Gy, with most of the increase occurring in the interval from 0.1 to 1.0 Gy. For circulatory disease, the dose-response curvature was inverse, so that risk per unit dose was nearly halved by going from 0.01 t o 1.0 Gy weighted absorbed dose, although there were substantial uncertainties. In general, there were higher radiation risks for females compared to males. This was true for solid cancer and circulatory disease overall, as well as for lung, breast, stomach and the group of other solid cancers, and was the case whether relative or absolute rate projection models were employed; however, for leukemia this pattern was reversed. Risk estimates varied somewhat between populations, with lower cancer risks in aggregate for China and Russia, but higher circulatory disease risks for Russia, particularly using the relative rate model. There was more pronounced variation for certain cancer sites and certain types of projection models, so that breast cancer risk was markedly lower in China and Japan using a relative rate model, but the opposite was the case for stomach cancer. There was less variation between countries using the absolute rate models for stomach cancer and breast cancer, but this was not the case for lung cancer and the group of other solid cancers, or for circulatory disease.

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Effect of follow-up period on minimal-significant dose in the atomic-bomb survivor studies.

Publications

Effect of follow-up period on minimal-significant dose in the atomic-bomb survivor studies.

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