Studies Of Atomic Bomb Survivors Research Articles

Relationship between radiation dose and markers of insulin resistance and inflammation in atomic bomb survivors.

In recent studies of childhood cancer survivors, diabetes has been considered a late effect associated with high therapeutic doses of radiation therapy. Our recent study of atomic bomb (A-bomb) survivors also suggested an association between radiation dose and diabetes incidence, with exposure city and age at exposure as radiation dose effect modifiers. Insulin resistance mediated by systemic inflammation and abnormal body composition has been suggested as a possible primary mechanism for the incidence of diabetes after total body irradiation, however, no studies have examined low-to- moderate radiation exposure (<4 Gy) and insulin resistance in A-bomb survivors. To examine the association between radiation dose and markers of inflammation and insulin resistance. This study investigated 3,152 survivors who underwent a health examination between 2008 and 2012 and who were younger than 15 years at exposure. Multivariate linear regression analyses were used to evaluate the radiation effects on levels of markers of inflammation and insulin resistance. Radiation dose was significantly and positively associated with levels of CRP, triglycerides, homeostasis model assessment of β-cell function (HOMA-β), and HOMA of insulin resistance (HOMA-IR) after adjustment for relevant covariates including sex, city, and age at exposure. Adiponectin and HDL cholesterol levels were also associated significantly and negatively with radiation dose. However, city was not a dose modifier of the radiation response on these markers of inflammation and insulin resistance. Insulin resistance might be a possible factor in the radiation related diabetes incidence in the A-bomb survivors.

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. We also summarize results of pooled studies. These summaries are necessarily brief, but we provide references to more detailed information. We discuss possible future directions of study, to include assessment of susceptible populations, and possible new populations, data sources, study designs and methods of analysis.

If You Torture Your Data Long Enough, It Will Confess to Anything: On the Epidemiological Basis of the LNT Model.

This note deals with epidemiological data interpretation supporting the linear no-threshold model, as opposed to emerging evidence of adaptive response and hormesis from molecular biology in vitro and animal models. Particularly, the US-Japan Radiation Effects Research Foundation's lifespan study of atomic bomb survivors is scrutinized. We stress the years-long lag of the data processing after data gathering and evolving statistical models and methodologies across publications. The necessity of cautious interpretation of radiation epidemiology results is emphasized.

Further analysis of incidence of multiple myeloma among atomic-bomb survivors, 1950 to 1994.

Multiple myeloma (MM) predominantly occurs in older persons and its diagnosis depends on pathological and laboratory findings. Epidemiological studies have provided inconsistent results on relationship between radiation exposure and MM. The Life Span Study (LSS) of atomic bomb (A-bomb) survivors has not shown a statistically significant radiation risk for MM. We studied previously reported MM cases diagnosed between 1950 and 1994 in the LSS and assessed diagnostic certainty based on histological and clinical features. Among 122 incident MM cases, 67 were classified as definite, 23, probable and 32, undetermined. The incidence rate increased with attained age and was highest in the oldest age group of over 70 years. For definite MM, Poisson regression dose response analysis showed an elevated, though not statistically significant, radiation risk with an estimated excess relative risk (ERR) per Gy of 0.44 (95%CI:<-0.02, 2.4), which was markedly higher than the previously reported ERR/Gy of -0.02 (95% CI: -0.24,0.75) that included cases with undetermined diagnostic certainty. The present case series included 24 persons with MM diagnosed after participating in M-protein screening offered to a clinical subset of the LSS members. Exclusion of screen-detected cases led to a higher radiation risk estimate, which was not statistically significant. A large number of young survivors exposed before age 20 years were younger than 70 years in the current follow-up period, but will reach ages with rapidly increasing MM rates. Future follow-up data with improved diagnostic certainty will improve understanding of long-term effects of radiation exposure on MM in this cohort.

Fetal atomic bomb survivor dosimetry using the J45 series of pregnant female phantoms with realistic survivor exposure scenarios: comparisons to dose estimates in the DS02 system.

A significant source of information on radiation-induced biological effects following in-utero irradiation stems from studies of atomic bomb survivors who were pregnant at the time of exposure in Hiroshima, and to a lesser extent, from survivors in Nagasaki. Dose estimates to the developing fetus for these survivors have been assigned in prior dosimetry systems of the Radiation Effects Research Foundation as the dose to the uterine wall within the non-pregnant adult stylized phantom, originally designed for the dosimetry system DS86 and then carried forward in DS02. In a prior study, a new J45 (Japanese 1945) series of high-resolution phantoms of the adult pregnant female at 8weeks, 15weeks, 25weeks, and 38-weeks post-conception was presented. Fetal and maternal organ doses were estimated by computationally exposing the pregnant female phantom series to DS02 free-in-air cumulative photon and neutron fluences at three distances from the hypocenter at both Hiroshima and Nagasaki under idealized frontal (AP) and isotropic (ISO) particle incidence. In this present study, this work was extended using realistic angular fluences (480 directions) from the DS02 system for seven radiation source terms, nine different radiation dose components, and five shielding conditions. In addition, to explore the effects of fetal position within the womb, four new phantoms were created and the same irradiation scenarios were performed. General findings are that the current DS02 fetal dose surrogate overestimates values of fetal organ dose seen in the J45 phantoms towards the cranial end of the fetus, especially in the later stages of pregnancy. For example, for in-open exposures at 1000m in Hiroshima, the ratio of J45 fetal brain dose to DS02 uterine wall dose is 0.90, 0.82, and 0.70 at 15weeks, 25weeks, and 38-weeks, respectively, for total gamma exposures, and are 0.64, 0.44, and 0.37 at these same gestational ages for total neutron exposures. For organs in the abdominal and pelvic regions of the fetus, dose gradients across gestational age flatten and later reverse, so that DS02 fetal dosimetry begins to underestimate values of fetal organ dose as seen in the J45 phantoms. For example, for the same exposure scenario, the ratios of J45 fetal kidney dose to DS02 uterine wall dose are about 1.09 from 15 to 38weeks for total gamma dose, and are 1.30, 1.56, and 1.75 at 15weeks, 25weeks, and 38weeks, respectively, for the total neutron dose. Results using the new fetal positioning phantoms show this trend reversing for a head-up, breach fetal position. This work supports previous findings that the J45 pregnant female phantom series offers significant opportunities for gestational age-dependent assessment of fetal organ dose without the need to invoke the uterine wall as a fetal organ surrogate.

Radiation-induced bystander effect and its clinical implications.

For many years, targeted DNA damage caused by radiation has been considered the main cause of various biological effects. Based on this paradigm, any small amount of radiation is harmful to the organism. Epidemiological studies of Japanese atomic bomb survivors have proposed the linear-non-threshold model as the dominant standard in the field of radiation protection. However, there is increasing evidence that the linear-non-threshold model is not fully applicable to the biological effects caused by low dose radiation, and theories related to low dose radiation require further investigation. In addition to the cell damage caused by direct exposure, non-targeted effects, which are sometimes referred to as bystander effects, abscopal effects, genetic instability, etc., are another kind of significant effect related to low dose radiation. An understanding of this phenomenon is crucial for both basic biomedical research and clinical application. This article reviews recent studies on the bystander effect and summarizes the key findings in the field. Additionally, it offers a cross-sectional comparison of bystander effects caused by various radiation sources in different cell types, as well as an in-depth analysis of studies on the potential biological mechanisms of bystander effects. This review aims to present valuable information and provide new insights on the bystander effect to enlighten both radiobiologists and clinical radiologists searching for new ways to improve clinical treatments.

Radon-222 and Leukemia.

Leukemia was the first medically observed human cancer related to ionizing radiation in the 1945 follow-up study of atomic bomb survivors. The bone exposure and dose calculated here are based on the measured solubility of the noble gas 222 Rn in blood. A fraction of the 222 Rn gas in blood distributes as dissolved gas to all organs, with the fraction depending upon the blood flow rate to the organ. The exposure and dose calculated are for men and women based on measurements made for the blood flow rate to the femur, the largest bone in the human skeleton. The annual exposure and dose estimated for continuous 222 Rn inhalation of 100 Bq m -3 are very low and unlikely to cause leukemia. Other neurological issues, from lifetime exposure to low activity concentrations of 222 Rn alpha particle exposure in bone, are unknown.

Effect of exposure to radiation caused by an atomic bomb on endothelial function in atomic bomb survivors.

The purpose of this study was to evaluate the effects of exposure to radiation caused by an atomic bomb in atomic bomb survivors on vascular function and vascular structure and to evaluate the relationships of radiation dose from the atomic bomb with vascular function and vascular structure in atomic bomb survivors. Flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) as indices of vascular function, brachial-ankle pulse wave velocity (baPWV) as an index of vascular function and vascular structure, and brachial artery intima-media thickness (IMT) as an index of vascular structure were measured in 131 atomic bomb survivors and 1,153 control subjects who were not exposed to the atomic bomb. Ten of the 131 atomic bomb survivors with estimated radiation dose in a cohort study of Atomic Bomb Survivors in Hiroshima were enrolled in the study to evaluate the relationships of radiation dose from the atomic bomb with vascular function and vascular structure. There was no significant difference in FMD, NID, baPWV, or brachial artery IMT between control subjects and atomic bomb survivors. After adjustment of confounding factors, there was still no significant difference in FMD, NID, baPWV, or brachial artery IMT between control subjects and atomic bomb survivors. Radiation dose from the atomic bomb was negatively correlated with FMD (ρ = -0.73, P = 0.02), whereas radiation dose was not correlated with NID, baPWV or brachial artery IMT. There were no significant differences in vascular function and vascular structure between control subjects and atomic bomb survivors. Radiation dose from the atomic bomb might be negatively correlated with endothelial function.

The Association of Radiation Exposure with Stable Chromosome Aberrations in Atomic Bomb Survivors Based on DS02R1 Dosimetry and FISH Methods.

The frequency of stable chromosome aberrations (sCA) in lymphocytes is a recognized radiation biological dosimeter. Its analysis can provide insights into factors that affect individual susceptibility as well as into the adequacy of radiation dose estimates used in studies of atomic bomb survivors. We analyzed the relationship between atomic bomb radiation exposure using the most recent DS02R1 dose estimates and the frequency of sCA as determined by FISH in 1,868 atomic bomb survivors. We investigated factors that may affect the background sCA rate and the shape and magnitude of the dose response. As in previous analyses of sCA in atomic bomb survivors that were based on Giemsa staining methods and used older DS86 dose estimates, the relationship between radiation dose and sCA rate was significant (P < 0.0001) with a linear-quadratic relationship at lower doses that did not persist at higher doses. As before, age at the time of the bombing and type of radiation shielding were significant dose-effect modifiers (P < 0.0001), but in contrast the difference in dose response by city was not so pronounced (P = 0.026) with a city effect not evident at doses below 1.25Gy. Background sCA rate increased with age at the time of examination (P < 0.0001), but neither sex, city, nor smoking was significantly associated with background rate. Based on FISH methods and recent dosimetry, the relationship between radiation dose and sCA frequency is largely consistent with previous findings, although the lesser importance of city as an effect modifier may reflect better dosimetry as well as more reproducible scoring of sCA. The persisting difference in sCA dose response by shielding category points to remaining problems with the accuracy or precision of radiation dose estimates in some A-bomb survivors.

New Insights into the Understanding of Mechanisms of Radiation-Induced Heart Disease.

Cancer patients who receive high-dose thoracic radiotherapy may develop radiation-induced heart disease (RIHD). The clinical presentation of RIHD comprises coronary artery atherosclerosis, valvular disease, pericarditis, cardiomyopathy, and conduction defects. These complications have significantly reduced due to the improved radiotherapy techniques. However, such methods still could not avoid heart radiation exposure. Furthermore, people who received relatively low-dose radiation exposures have exhibited significantly elevated RIHD risks in cohort studies of atomic bomb survivors and occupational exposures. The increased potential in exposure to natural and artificial ionizing radiation sources has emphasized the necessity to understand the development of RIHD. The pathological processes of RIHD include endothelial dysfunction, inflammation, fibrosis, and hypertrophy. The underlying mechanisms may involve the changes in oxidative stress, DNA damage response, telomere erosion, mitochondrial dysfunction, epigenetic regulation, circulation factors, protein post-translational modification, and metabolites. This review will discuss the recent advances in the mechanisms of RIHD at cellular and molecular levels.

Radiation-induced hematopoietic disorders

Hematopoietic stem cells are one of the most sensitive tissues to radiation exposure. Epidemiological studies of atomic bomb survivors in Nagasaki and Hiroshima revealed a radiation dose-response relationship for acute myeloid leukemia, acute lymphoblastic leukemia, and Chronic myelogenous leukemia. In our study of myelodysplastic syndrome (MDS) in Nagasaki, the relative risk was higher in the proximal-exposed group. Additionally, the frequency of chromosome abnormalities associated with poor prognosis was higher in the proximal-exposed group than in the non-exposed group. However, no association between the exposure distance and prognosis was observed. We used next-generation sequencing to analyze the role of genetic abnormalities in the development of MDS. The results indicated that genetic mutations related to DNA methylation pathways, which are frequently observed in de novo MDS, were considerably less frequent in the proximal-exposed than in the distal-exposed group. These results suggest that the pathogenesis of MDS in atomic bomb survivors may be different from that of treatment-related and de novo MDS.

Biological Effects of Neutron Radiation: An Overview

Exposure of human body to neutrons occurs in radiotherapy using high-energy radiations. This review summarizes knowledges related to biological effects of neutrons, including those obtained in recent projects in Japan and Europe. A study of Japanese atomic bomb survivors with recently revised dosimetry indicated very high relative biological effectiveness (RBE) of 25-80 (as point estimates) regarding cancer risk. Animal studies indicate RBE of 2-100 or even higher regarding cancer induction, which seem to have a peak around ～1 MeV. Evidence suggests that these values depend on the age and sex. Reported RBE regarding the effects on the lens of the eye is in a similar range and sometimes very high. Regarding other tissue reactions, reported RBE values range from 2-10. Experiments at the cellular level have reported RBE of 1-5 regarding cell killing, 2-20 regarding induction of mutations (with a peak at ～1 MeV), and ～1 regarding induction of DNA double strand breaks. A simulation study predicted that the RBE of induction of complex DNA breaks peaks at ～1 MeV with a value of ～17. The complex breaks produced are likely to be far less in amount than simple DNA breaks, leading to a subtle increase in the yield of total DNA breaks; however, these complex damages may be very efficient in inducing mutations and cancer. Thus, the combination of the yield of complex DNA damage and its efficacy in inducing cancer is considered to underlie the high RBE of neutrons regarding cancer risk.

Lifetime Risk Assessment of Lung Cancer Incidence for Nonsmokers in Japan Considering the Joint Effect of Radiation and Smoking Based on the Life Span Study of Atomic Bomb Survivors

Background: The lifetime risk of lung cancer incidence due to radiation for nonsmokers is overestimated because of the use of the average cancer baseline risk among a mixed population, including smokers. In recent years, the generalized multiplicative (GM)-excess relative risk (ERR) model has been developed in the life span study of atomic bomb survivors to consider the joint effect of radiation and smoking. Based on this background, this paper discusses the issues of radiation risk assessment considering smoking in two parts.Materials and Methods: In Part 1, we proposed a simple method of estimating the baseline risk for nonsmokers using current smoking data. We performed sensitivity analysis on baseline risk estimation to discuss the birth cohort effects. In Part 2, we applied the GM-ERR model for Japanese smokers to calculate lifetime attributable risk (LAR). We also performed a sensitivity analysis using other ERR models (e.g., simple additive (SA)-ERR model).Results and Discussion: In Part 1, the lifetime baseline risk from mixed population including smokers to nonsmokers decreased by 54% (44%–60%) for males and 24% (18%–29%) for females. In Part 2, comparison of LAR between SA- and GM-ERR models showed that if the radiation dose was ≤200 mGy or less, the difference between these ERR models was within the standard deviation of LAR due to the uncertainty of smoking information.Conclusion: The use of mixed population for baseline risk assessment overestimates the risk for lung cancer due to low-dose radiation exposure in Japanese males.

The possible impact of passive smoke exposure on radiation-related risk estimates for lung cancer among women: the life span study of atomic bomb survivors

Purpose Analyses of the Life Span Study cohort of atomic bomb survivors have shown a statistically significant sex difference in the excess risk of incident lung cancer due to radiation exposure, with the radiation-related excess relative risk per gray (ERR/Gy) for women approximately 4 times that for men, after accounting for active smoking. We sought to determine the extent to which this risk difference could be explained by adjustment for passive smoke exposure, which is a known risk factor for lung cancer that was not measured among Life Span Study participants, and which could be particularly influential among female never-smokers. Materials and methods The Life Span Study includes survivors of the atomic bombings of Hiroshima and Nagasaki and city residents who were not in either city at the time of the bombings, matched to survivors on city, sex, and age. First primary lung cancers were identified from population-based cancer registries between 1958 and 2009. Data on active smoking were obtained from mailed surveys and in-person questionnaires (1965–1991). We calculated passive smoke exposure for female never-smokers by attributing smoking pack-years at various intensities (5–50%) based on smoking patterns among men, stratified by city, birth year, radiation dose, and lung cancer status. Poisson regression models with additive and multiplicative interactions between radiation dose and smoking were used to estimate sex-specific radiation-related excess relative risks for lung cancer. Results During the study period, 2,446 first primary lung cancers were identified among 105,444 study participants. On average, male smokers started smoking 19.5 cigarettes per day at 21.5 years old. Partially attributing male smoking patterns to female never-smokers—to approximate passive smoke exposure—yielded lower radiation-related ERR/Gy estimates for women under a multiplicative radiation-smoking interaction model, leading to a lower female-to-male ratio of ERR/Gy estimates; however, this difference was evident only at very high passive smoke intensities. Under an additive radiation-smoking interaction model, the results were unchanged. Conclusions Our results are consistent with the possibility that failure to account for passive smoke might contribute, in small part, to the higher radiation risk estimates for lung cancer among women compared to men in the Life Span Study.

Organ Dose Reconstruction Applicable for a Japanese Nuclear Worker Cohort: J-EPISODE.

An evaluation of cancer risk based on organ-absorbed dose is underway for the Japanese Epidemiological Study on Low-Dose Radiation Effects (J-EPISODE), which has analyzed health effects in association with radiation exposure evaluated with the personal dose equivalent Hp(10). Although the concept of effective dose and its operational definition of Hp(10) are widely used for radiological protection purposes, effective dose is not recommended for epidemiological evaluation. Organ-absorbed dose was instead adopted for the IARC 15-Country Collaborative study (15-Country study), the International Nuclear Workers Study (INWORKS), the Mayak worker study, and the Life Span Study (LSS) of atomic bomb survivors. The reconstruction method in J-EPISODE followed in principle the approach adopted in the 15-Country Study. As part of the approach of J-EPISODE, a conversion factor from photon dosimeter reading to air kerma was developed using dosimeter response data, which were measured by the experiment using an anthropomorphic phantom, and it was confirmed that the 15-Country study’s assumption of photon energy and geometry distribution in a work environment applied to Japanese nuclear workers. This article focuses on a method for reconstructing the conversion factor from photon dosimeter reading to organ-absorbed photon dose for a Japanese nuclear worker cohort. The model for estimating the conversion factor was defined under the assumption of a lognormal distribution from three concerned bias factors: (1) a dosimeter reading per air kerma, i.e., dosimeter response; (2) an organ-absorbed dose per air kerma; and (3) a factor relating to the differences in dose concepts and calibration practices between the roentgen dosimeter era and the present. Dosimeter response data were cited from the companion paper. Data on organ-absorbed photon dose per air kerma were estimated using a voxel phantom with the average Japanese adult male height and weight. The bias factor for the recorded dose in the roentgen era was defined, considering the backscatter radiation from the human body. The estimated values of organ-absorbed photon dose per air kerma were almost the same as those in ICRP Publication 116, revealing that the effect of differences in body size was almost negligible. The conversion factors from dosimeter reading to organ-absorbed dose were estimated by period (the roentgen era or from then), nuclear facility type (nuclear power plant or other), dosimeter type, and tissue or organ. The estimated conversion factors ranged from 0.7 to 0.9 (Gy Sv−1). The estimated cumulative organ-absorbed photon dose for the participants of J-EPISODE demonstrated that organ-absorbed dose values were approximately 0.8 times the recorded doses if neglecting dose-unit differences. J-EPISODE reconstructed an organ-absorbed dose conversion factor and will evaluate the risk of cancer mortality and morbidity using the organ-absorbed dose in the future.

Mortality among medical radiation workers in the United States, 1965–2016

Background Estimates of radiation risks following prolonged exposures at low doses and low-dose rates are uncertain. Medical radiation workers are a major component of the Million Person Study (MPS) of low-dose health effects. Annual personal dose equivalents, H P(10), for individual workers are available to facilitate dose-response analyses for lung cancer, leukemia, ischemic heart disease (IHD) and other causes of death. Materials and methods The Landauer, Inc. dosimetry database identified 109,019 medical and associated radiation workers first monitored 1965–1994. Vital status and cause of death were determined through 2016. Mean absorbed doses to red bone marrow (RBM), lung, heart, and other organs were estimated by adjusting the recorded H P(10) for each worker by scaling factors, accounting for exposure geometry, the energy of the incident photon radiation, sex of the worker and whether an apron was worn. There were 4 exposure scenarios: general radiology characterized by low-energy x-ray exposure with no lead apron use, interventional radiologists/cardiologists who wore aprons, nuclear medicine personnel and radiation oncologists exposed to high-energy photon radiation, and other workers. Standardized mortality ratio (SMR) analyses were performed. Cox proportional hazards models were used to estimate organ-specific radiation risks. Results Overall, 11,433 deaths occurred (SMR 0.60; 95%CI 0.59,0.61), 126 from leukemia other than chronic lymphocytic leukemia (CLL), 850 from lung cancer, and 1654 from IHD. The mean duration of monitoring was 23.7 y. The excess relative rate (ERR) per 100 mGy was estimated as 0.10 (95% CI −0.34, 0.54) for leukemia other than CLL, 0.15 (0.02, 0.27) for lung cancer, and −0.10 (–0.27, 0.06) for IHD. The ERR for lung cancer was 0.16 (0.01, 0.32) among the 55,218 male workers and 0.09 (–0.19, 0.36) among the 53,801 female workers; a difference that was not statistically significant (p-value = 0.23). Conclusions Medical radiation workers were at increased risk for lung cancer that was higher among men than women, although this difference was not statistically significant. In contrast, the study of Japanese atomic bomb survivors exposed briefly to radiation in 1945 found females to be nearly 3 times the radiation risk of lung cancer compared with males on a relative scale. For medical workers, there were no statistically significant radiation associations with leukemia excluding CLL, IHD or other specific causes of death. Combining these data with other cohorts within the MPS, such as nuclear power plant workers and nuclear submariners, will enable more precise estimates of radiation risks at relatively low cumulative doses.

Prospects and status of the dosimetry system for atomic bomb survivor cohort study conducted at Research Institute for Radiation Biology and Medicine of Hiroshima University.

ABSTRACTThe Research Institute for Radiation Biology and Medicine (RIRBM) of Hiroshima University has been conducting a cohort study of atomic bomb survivors (ABS). Cohort members include those who were issued an Atomic Bomb Health Handbook from the Hiroshima local government. A series of dosimetry systems for the ABS were developed at RIRBM to evaluate the health effects associated with radiation exposure. The framework used to estimate individual doses in our dosimetry systems for ABS is mainly based on the Dosimetry System 86, and its revisions developed by the Radiation Effect Research Foundation. This article describes the design and computational principles for the dosimetry systems in RIRBM and the history of the revisions, from the first version of the system, ABS93D, to the most recent version, ABS16D. We then provide a perspective for further improvement and application of the dosimetry system.

Conclusions and Suggestions on Low-Dose and Low-Dose Rate Radiation Risk Estimation Methodology

Background: For radiological protection and control, the International Commission on Radiological Protection (ICRP) provides the nominal risk coefficients related to radiation exposure, which can be extrapolated using the excess relative risk and excess absolute risk obtained from the Life Span Study of atomic bomb survivors in Hiroshima and Nagasaki with the dose and dose-rate effectiveness factor (DDREF). Materials and Methods: Since it is impossible to directly estimate the radiation risk at doses less than approximately 100 mSv only from epidemiological knowledge and data, support from radiation biology is absolutely imperative, and thus, several national and international bodies have advocated the importance of bridging knowledge between biology and epidemiology. Because of the accident at the Tokyo Electric Power Company (TEPCO)’s Fukushima Daiichi Nuclear Power Station in 2011, the exposure of the public to radiation has become a major concern and it was considered that the estimation of radiation risk should be more realistic to cope with the prevailing radiation exposure situation. Results and Discussion: To discuss the issues from wide aspects related to radiological protection, and to realize bridging knowledge between biology and epidemiology, we have established a research group to develop low-dose and low-dose-rate radiation risk estimation methodology, with the permission of the Japan Health Physics Society. Conclusion: The aim of the research group was to clarify the current situation and issues related to the risk estimation of low-dose and low-dose-rate radiation exposure from the viewpoints of different research fields, such as epidemiology, biology, modeling, and dosimetry, to identify a future strategy and roadmap to elucidate a more realistic estimation of risk against low-dose and low-dose-rate radiation exposure.

Gastrointestinal Cancer Survival and Radiation Exposure among Atomic Bomb Survivors: The Life Span Study.

Radiation exposure is an established risk factor for the development of several forms of cancer, including gastrointestinal cancers. However, few studies have investigated the relationship between prediagnostic radiation exposure and survival after cancer diagnosis. Participants in the Life Span Study (LSS) of atomic bomb survivors who were diagnosed with a first primary invasive stomach, colon, or rectal cancer between 1958 and 2009 were followed for mortality during 1958-2014. Cox regression models were used to calculate HRs and 95% confidence intervals (CI) for associations of radiation dose from atomic bomb exposure with survival (cancer-specific and overall) after cancer diagnosis. Analyses were adjusted for city of primary exposure, sex, age at diagnosis, and year of diagnosis. We identified 7,728 eligible patients with cancer for analysis. We observed no statistically significant associations between radiation dose and cancer-specific survival among LSS participants with a gastrointestinal cancer. Higher radiation doses (≥1 Gy) were suggestively, but not significantly, associated with modestly poorer cancer-specific survival for colon cancer only (HR, 1.38; 95% CI, 0.90-2.12), and were associated with poorer overall survival regardless of cancer site. Although radiation exposure is associated with increased risk of gastrointestinal cancer incidence and mortality, study results are inconclusive about an association between prediagnostic radiation exposure and survival after gastrointestinal cancer diagnosis. Radiation exposure from the atomic bomb before gastrointestinal cancer diagnosis was not associated with cancer survival, but should be evaluated in relation to survival for other cancer types.

Risk of cancer associated with low-dose radiation exposure: comparison of results between the INWORKS nuclear workers study and the A-bomb survivors study

The Life Span Study (LSS) of Japanese atomic bomb survivors has served as the primary basis for estimates of radiation-related disease risks that inform radiation protection standards. The long-term follow-up of radiation-monitored nuclear workers provides estimates of radiation-cancer associations that complement findings from the LSS. Here, a comparison of radiation-cancer mortality risk estimates derived from the LSS and INWORKS, a large international nuclear worker study, is presented. Restrictions were made, so that the two study populations were similar with respect to ages and periods of exposure, leading to selection of 45,625 A-bomb survivors and 259,350 nuclear workers. For solid cancer, excess relative rates (ERR) per gray (Gy) were 0.28 (90% CI 0.18; 0.38) in the LSS, and 0.29 (90% CI 0.07; 0.53) in INWORKS. A joint analysis of the data allowed for a formal assessment of heterogeneity of the ERR per Gy across the two studies (P = 0.909), with minimal evidence of curvature or of a modifying effect of attained age, age at exposure, or sex in either study. There was evidence in both cohorts of modification of the excess absolute risk (EAR) of solid cancer by attained age, with a trend of increasing EAR per Gy with attained age. For leukemia, under a simple linear model, the ERR per Gy was 2.75 (90% CI 1.73; 4.21) in the LSS and 3.15 (90% CI 1.12; 5.72) in INWORKS, with evidence of curvature in the association across the range of dose observed in the LSS but not in INWORKS; the EAR per Gy was 3.54 (90% CI 2.30; 5.05) in the LSS and 2.03 (90% CI 0.36; 4.07) in INWORKS. These findings from different study populations may help understanding of radiation risks, with INWORKS contributing information derived from cohorts of workers with protracted low dose-rate exposures.