Recommendations on statistical approaches to account for dose uncertainties in radiation epidemiologic risk models.

Purpose: Epidemiological studies of stochastic radiation health effects such as cancer, meant to estimate risks of the adverse effects as a function of radiation dose, depend largely on estimates of the radiation doses received by the exposed group under study. Those estimates are based on dosimetry that always has uncertainty, which often can be quite substantial. Studies that do not incorporate statistical methods to correct for dosimetric uncertainty may produce biased estimates of risk and incorrect confidence bounds on those estimates.

A Historical Survey of Key Epidemiological Studies of Ionizing Radiation Exposure.

In this article we review the history of key epidemiological studies of populations exposed to ionizing radiation. We highlight historical and recent findings regarding radiation-associated risks for incidence and mortality of cancer and non-cancer outcomes with emphasis on study design and methods of exposure assessment and dose estimation along with brief consideration of sources of bias for a few of the more important studies. We examine the findings from the epidemiological studies of the Japanese atomic bomb survivors, persons exposed to radiation for diagnostic or therapeutic purposes, those exposed to environmental sources including Chornobyl and other reactor accidents, and occupationally exposed cohorts.

The Use of Joint Models in Analysis of Aggregate Endpoints in RERF Cohort Studies.

In radiation risk estimation based on the Radiation Effects Research Foundation (RERF) cohort studies, one common analysis is Poisson regression on radiation dose and background and effect modifying variables of an aggregate endpoint such as all solid cancer incidence or all non-cancer mortality. As currently performed, these analyses require selection of a surrogate radiation organ dose, (e.g.

Congenital Malformations and Perinatal Deaths Among the Children of Atomic Bomb Survivors: A Reappraisal.

From 1948 to 1954, the Atomic Bomb Casualty Commission conducted a study of pregnancy outcomes among births to atomic bomb survivors (Hiroshima and Nagasaki, Japan) who had received radiation doses ranging from 0 Gy to near-lethal levels. Past reports (1956, 1981, and 1990) on the cohort did not identify significant associations of radiation exposure with untoward pregnancy outcomes, such as major congenital malformations, stillbirths, or neonatal deaths, individually or in aggregate. We reexamined the risk of major congenital malformations and perinatal deaths in the children of atomic bomb survivors (n = 71,603) using fully reconstructed data to minimize the potential for bias, using refined estimates of the gonadal dose from Dosimetry System 2002 and refined analytical methods for characterizing dose-response relationships.

Dosimetric Impact of a New Computational Voxel Phantom Series for the Japanese Atomic Bomb Survivors: Methodological Improvements and Organ Dose Response Functions.

Owing to recent advances in computational dosimetry tools, an update is warranted for the dosimetry system for atomic bomb survivors that was established by the Joint U.S.Japan Working Group on the Reassessment of Atomic Bomb Dosimetry in 2002 (DS02).

Lifetime Mortality Risk from Cancer and Circulatory Disease Predicted from the Japanese Atomic Bomb Survivor Life Span Study Data Taking Account of Dose Measurement Error.

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.

Modifying Effect of Chronic Atrophic Gastritis on Radiation Risk for Noncardia Gastric Cancer According to Histological Type.

The findings from previously published studies have suggested that radiation exposure is associated with increased mortality and incidence of gastric cancer. However, few cohort studies have incorporated risk factors such as Helicobacter pylori (H. pylori) infection or chronic atrophic gastritis (CAG).

Epidemiological Studies of Low-Dose Ionizing Radiation and Cancer: Rationale and Framework for the Monograph and Overview of Eligible Studies.

Whether low-dose ionizing radiation can cause cancer is a critical and long-debated question in radiation protection. Since the Biological Effects of Ionizing Radiation report by the National Academies in 2006, new publications from large, well-powered epidemiological studies of low doses have reported positive dose-response relationships. It has been suggested, however, that biases could explain these findings.

Strengths and Weaknesses of Dosimetry Used in Studies of Low-Dose Radiation Exposure and Cancer.

Background: A monograph systematically evaluating recent evidence on the dose-response relationship between low-dose ionizing radiation exposure and cancer risk required a critical appraisal of dosimetry methods in 26 potentially informative studies.

Methods: The relevant literature included studies published in 2006-2017. Studies comprised case-control and cohort designs examining populations predominantly exposed to sparsely ionizing radiation, mostly from external sources, resulting in average doses of no more than 100 mGy.

Dosimetric Impact of a New Computational Voxel Phantom Series for the Japanese Atomic Bomb Survivors: Pregnant Females.

An important cohort of the atomic bomb survivors are women who were pregnant when exposed to the photon and neutron fields at both Hiroshima and Nagasaki, as well as their children who were exposed . Estimates of organ dose to the developing fetus allow for the development of dose-dependent and gestational age-dependent models of deterministic (e.g.

Assessing the Relative Biological Effectiveness of Neutrons across Organs of Varying Depth among the Atomic Bomb Survivors.

When assessing radiation-related risk among the atomic bomb survivors, choices in modeling approach can have an important impact on the results, which are then used to inform radiation protection standards throughout the world. The atomic bombings of Hiroshima and Nagasaki produced a mixed-field radiation exposure from two sources: neutrons and gamma rays. Neutrons are more densely ionizing and cause greater biological damage per unit absorbed dose, resulting in greater relative biological effectiveness (RBE) than gamma rays.

Effect of Heterogeneity in Background Incidence on Inference about the Solid-Cancer Radiation Dose Response in Atomic Bomb Survivors.

A recent analysis of solid cancer incidence in the Life Span Study of atomic bomb survivors (Hiroshima and Nagasaki, Japan) found evidence of a nonlinear, upwardly curving radiation dose response among males but not among females. Further analysis of this new and unexpected finding was necessary. We used two approaches to investigate this finding.

Association of Weight Fluctuation With Mortality in Japanese Adults.

Importance: Weight cycling is associated with the risk of mortality from heart disease, but many studies have not distinguished between simple nonlinear (monotone) weight changes and more complex changes that reflect fluctuations.

Objective: To assess whether extreme body weight variation is associated with mortality after controlling for nonlinear weight changes.

Design, Setting, And Participants: In this prospective clinical cohort study, 4796 Japanese atomic bomb survivors were examined in the clinic as part of a biennial health examination and research program.

Correction to: Dose-responses for mortality from cerebrovascular and heart diseases in atomic bomb survivors: 1950-2003.

The article Dose-responses for mortality from cerebrovascular and heart diseases in atomic bomb survivors: 1950-2003, written by Helmut Schöllnberger.

Dosimetric Impact of a New Computational Voxel Phantom Series for the Japanese Atomic Bomb Survivors: Children and Adults.

One of the largest sources of data on radiation exposure in humans is the study of the atomic bomb survivors at Hiroshima and Nagasaki, Japan performed by the Radiation Effects Research Foundation (RERF). As part of their retrospective dosimetry efforts for the atomic bomb survivors, RERF published two core systems: Dosimetry System 1986 (DS86) and Dosimetry System 2002 (DS02). Due to computing limitations at the time, only three stylized phantoms (an infant, child and adult) were used in DS86 and DS02 to represent the entire Japanese population.