Atomic Bomb Survivors In Hiroshima Research Articles

The Lesser Evil: Plutonium-239 or Uranium-235? A Study on F0 Atomic Bomb Survivors

‘All models are wrong, but some models are useful.’ Radioactivity is a life-detrimental exposure that increases individuals’ susceptibility to cancer onset. The plasticity of the aging rate, expressed as d(log μ(x))/dx, has been informally acknowledged, often conflated with mortality rate μ(x) or risk log μ(x). A formal examination of this plasticity is lacking. The mortality schedule of irradiated F0 atomic bomb survivors in Hiroshima (U-235) and Nagasaki (Pu-239) at age exposure 40 - 45 (ATE45) can unveil the characteristics of hazard trajectories by isotope type and dosimetry. Based on the advantage derived from background radiation, an alternative population was employed during the comparative study. A dose-dependent relationship between radioactive isotope types and the rate of aging was presented in the frailty framework; _γ-Gompertz-Makeham_. Among survivors within the 0-5mGy range, an apparent pseudo-benefit initial mortality risk, linked to the distance from the epicenter, implies that mortality selection is influenced by both impact severity and natural frailty. Moreover, the standardized mortality ratio indicates a more pronounced impact of Pu-239 on age-specific mortality trajectories compared to U-235. In the 0-5mGy range, Pu-239 shows 11% (M) and 37% (F), while U-235 exhibits 4% (M) and 0.5% (F). Upon intense radiation exposure, variation in the human rate of aging exists within a 10-km radius from the epicenter, and gender sensitivity may be a significant contributor to mortality selection.

The Lesser Evil: Plutonium-239 or Uranium-235? A Study on F0 Atomic Bomb Survivors

‘All models are wrong, but some models are useful.’ Radioactivity is a life-detrimental exposure that increases individuals’ susceptibility to cancer onset. The plasticity of the rate of aging _d(log μ(x))/dx_ has never been formally addressed, as it has been casually inferred as mortality rate _μ(x)_ or risk _log μ(x)_. The mortality schedule of irradiated F0 atomic bomb survivors in Hiroshima (U-235) and Nagasaki (Pu-239) at age exposure 40 - 45 (ATE45) can unveil the characteristics of hazard trajectories by isotope type and dosimetry. Based on the advantage derived from background radiation, an alternative population was employed during the comparative study. A dose-dependent relationship between radioactive isotope types and the rate of aging was presented in the frailty framework; _γ-Gompertz-Makeham_. A pseudo-benefit initial mortality risk by distance to the epicenter was also observed among 0-5mGy survivors, suggesting that selection for mortality was determined by stringency from impact and frailty from natural selection. Furthermore, the standardized mortality ratio suggests Pu-239 has a more drastic effect on age-specific mortality trajectory than U-235; 0-5mGy, _Pu-239_ 11%(M) 37%(F); _U-235_ 4%(M) 0.5%(F). Upon intense radiation exposure, variation in the human rate of aging exists within a 10-km radius from the epicenter, and gender sensitivity may be a significant contributor to mortality selection.

Naive CD4 T Cells Highly Expressing the Inflammatory Chemokine Receptor CXCR3 Increase with Age and Radiation Exposure in Atomic Bomb Survivors.

The numbers of naive T cells that react to novel pathogens not yet encountered by an immune system, decrease during aging, mainly due to age-associated involution of the thymus. CD45RA+ naive CD4 T cells consist of heterogeneous populations, including highly CXCR3-expressing cells that appear during the homeostatic proliferation of naive T cells and exhibit enhanced type-1 inflammatory phenotypes. Based on previous evidence of radiation-associated reductions in thymic function and peripheral blood naive CD4 T cells, we hypothesized that the homeostatic proliferation of naive CD4 T cells compensates for deficits in peripheral T-cell populations after radiation injury, which may increase the proportion of CXCR3high cells in naive CD4 T cells and enhance inflammation. The statistical models employed in this study revealed positive associations between the number of CXCR3high naive CD4 T cells and age as well as radiation dose among 580 Hiroshima atomic bomb survivors. In addition, the CXCR3high cells in these survivors increased not only with the levels of homeostatic cytokines, IL6 and IL7, but also with those of inflammatory indicators, CXCL10 and CRP. These results suggest that thymic T-cell production deficiency due to radiation and aging results in enhanced homeostatic proliferation that drives the appearance of CXCR3high naive CD4 T cells poised for an inflammatory response. Molecular mechanisms and clinical relevance of increasing CXCR3high cells in naive CD4 T populations should be further investigated in the context of inflammatory disease development long after radiation exposure.

Early-life atomic-bomb irradiation accelerates immunological aging and elevates immune-related intracellular reactive oxygen species.

Reactive oxygen species (ROS) play an important role in immune responses; however, their excessive production and accumulation increases the risk of inflammation-related diseases. Although irradiation is known to accelerate immunological aging, the underlying mechanism is still unclear. To determine the possible involvement of ROS in this mechanism, we examined 10,023 samples obtained from 3752 atomic-bomb survivors in Hiroshima and Nagasaki, who participated in repeated biennial examinations from 2008 to 2016, for the effects of aging and radiation exposure on intracellular ROS (H2 O2 and O2 •- ) levels, percentages of T-cell subsets, and the effects of radiation exposure on the relationship between cell percentages and intracellular ROS levels in T-cell subsets. The cell percentages and intracellular ROS levels in T-cell subsets were measured using flow cytometry, with both fluorescently labeled antibodies and the fluorescent reagents, carboxy-DCFDA and hydroethidine. The percentages of naïve CD4+ and CD8+ T cells decreased with increasing age and radiation dose, while the intracellular O2 •- levels in central and effector memory CD8+ T cells increased. Additionally, when divided into three groups based on the percentages of naïve CD4+ T cells, intracellular O2 •- levels of central and effector memory CD8+ T cells were significantly elevated with the lowest radiation dose group in the naïve CD4+ T cells. Thus, the radiation exposure-induced decrease in the naïve CD4+ T cell pool size may reflect decreased immune function, resulting in increased intracellular ROS levels in central and effector memory CD8+ T cells, and increased intracellular oxidative stress.

SUMRAY: R and Python Codes for Calculating Cancer Risk Due to Radiation Exposure of a Population

Background: Quantitative risk assessments should be accompanied by uncertainty analyses of the risk models employed in the calculations. In this study, we aim to develop a computational code named SUMRAY for use in cancer risk projections from radiation exposure taking into account uncertainties. We also aim to make SUMRAY publicly available as a resource for further improvement of risk projection.Materials and Methods: SUMRAY has two versions of code written in R and Python. The risk models used in SUMRAY for all-solid-cancer mortality and incidence were those published in the Life Span Study of a cohort of the atomic bomb survivors in Hiroshima and Nagasaki. The confidence intervals associated with the evaluated risks were derived by propagating the statistical uncertainties in the risk model parameter estimates by the Monte Carlo method.Results and Discussion: SUMRAY was used to calculate the lifetime or time-integrated attributable risks of cancer under an exposure scenario (baseline rates, dose[s], age[s] at exposure, age at the end of follow-up, sex) specified by the user. The results were compared with those calculated using another well-known web-based tool, Radiation Risk Assessment Tool (Rad- RAT; National Institutes of Health), and showed a reasonable agreement within the estimated confidential interval. Compared with RadRAT, SUMRAY can be used for a wide range of applications, as it allows the risk projection with arbitrarily specified risk models and/or population reference data.Conclusion: The reliabilities of SUMRAY with the present risk-model parameters and their variance-covariance matrices were verified by comparing them with those of the other codes. The SUMRAY code is distributed to the public as an open-source code under the Massachusetts Institute of Technology license.

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.

Concepts of association between cancer and ionising radiation: accounting for specific biological mechanisms

The probability that an observed cancer was caused by radiation exposure is usually estimated using cancer rates and risk models from radioepidemiological cohorts and is called assigned share (AS). This definition implicitly assumes that an ongoing carcinogenic process is unaffected by the studied radiation exposure. However, there is strong evidence that radiation can also accelerate an existing clonal development towards cancer. In this work, we define different association measures that an observed cancer was newly induced, accelerated, or retarded. The measures were quantified exemplarily by Monte Carlo simulations that track the development of individual cells. Three biologically based two-stage clonal expansion (TSCE) models were applied. In the first model, radiation initiates cancer development, while in the other two, radiation has a promoting effect, i.e. radiation accelerates the clonal expansion of pre-cancerous cells. The parameters of the TSCE models were derived from breast cancer data from the atomic bomb survivors of Hiroshima and Nagasaki. For exposure at age 30, all three models resulted in similar estimates of AS at age 60. For the initiation model, estimates of association were nearly identical to AS. However, for the promotion models, the cancerous clonal development was frequently accelerated towards younger ages, resulting in associations substantially higher than AS. This work shows that the association between a given cancer and exposure in an affected person depends on the underlying biological mechanism and can be substantially larger than the AS derived from classic radioepidemiology.

Intracellular reactive oxygen species level in blood cells of atomic bomb survivors is increased due to aging and radiation exposure

Although reactive oxygen species (ROS) play important roles in immune responses, excessive ROS production and accumulation might enhance the risk of inflammation-related diseases. Moreover, impaired immune function and the acceleration of pre-clinically persistent inflammation due to aging and radiation exposure have been observed in atomic bomb (A-bomb) survivors more than 60 years post-exposure. Meanwhile, the effects of aging and radiation exposure on ROS production in immune cells have not been characterized. This study investigated the relationship between intracellular ROS (H2O2 and O2•−) levels in blood cells or T cell subsets and serum iron, ferritin, and C-reactive protein (CRP) levels, as well as how these variables are affected by age and radiation exposure in A-bomb survivors. We examined 2495 Hiroshima A-bomb survivors. Multiple linear regression models adjusted for confounding factors indicated that intracellular O2•− levels in monocytes, granulocytes, and lymphocytes, and particularly in memory CD8+ T cells, including effector memory and terminally differentiated effector memory CD8+ T cells, increased with radiation dose. Additionally, serum iron, ferritin, and CRP levels affected intracellular ROS levels in specific blood cell types and T cell subsets. Serum CRP levels increased significantly with increasing age and radiation dose. Finally, when divided into three groups according to serum CRP levels, dose-dependent increases in the intracellular O2•− levels in blood cells and central memory and effector memory CD8+ T cells were most prominently observed in the high-CRP group. These results suggest that an increase in the levels of certain intracellular ROS, particularly after radiation exposure, might be linked to enhanced inflammatory status, including elevated serum CRP levels and reduced serum iron levels. This study reveals that aging and radiation exposure increase oxidative stress in blood cells, which is involved in impaired immune function and accelerated pre-clinically persistent inflammation in radiation-exposed individuals.

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.

Screening for M-proteinemia consisting of monoclonal gammopathy of undetermined significance and multiple myeloma for 30years among atomic bomb survivors in Hiroshima.

Monoclonal gammopathy (M-proteinemia) is a premalignant plasma cell disorder. The prevalence of M-proteinemia increases with age and is affected by genetic or environmental factors. Atomic bomb (A-bomb) survivors in Hiroshima are in an age range when they are susceptible to M-proteinemia. The prevalence and incidence of M-proteinemia in Hiroshima A-bomb survivors were investigated for 30years (1989-2018) to examine the influence of radiation exposure. The overall prevalence of M-proteinemia among 38,602 A-bomb survivors was 2.4%. M-proteinemia prevalence at age 70years and monoclonal gammopathy of undetermined significance (MGUS) incidence were not associated with radiation exposure category. Males had a 2.30-fold higher prevalence and a 2.08-fold higher incidence than females. The risk of incidence for MGUS was 4.32-fold higher in persons aged < 10years at the time of the A-bombing and 2.56-fold higher in those aged 10-19years compared with those aged over 30years. IgG type M-proteinemia was common and the IgM type developed 5-8years later than other immunoglobulin types. Exposure to radiation was not clearly associated with the prevalence of M-proteinemia or incidence of MGUS in Hiroshima A-bomb survivors. However, males and those aged < 20years at A-bombing had higher susceptibility to MGUS.

In Memoriam: Mortimer L. Mendelsohn: (1 December, 1925-8 January, 2020).

In Memoriam: Mortimer L. Mendelsohn: (1 December, 1925-8 January, 2020).

ProZES: the methodology and software tool for assessment of assigned share of radiation in probability of cancer occurrence

ProZES is a software tool for estimating the probability that a given cancer was caused by preceding exposure to ionising radiation. ProZES calculates this probability, the assigned share, for solid cancers and hematopoietic malignant diseases, in cases of exposures to low-LET radiation, and for lung cancer in cases of exposure to radon. User-specified inputs include birth year, sex, type of diagnosed cancer, age at diagnosis, radiation exposure history and characteristics, and smoking behaviour for lung cancer. Cancer risk models are an essential part of ProZES. Linking disease and exposure to radiation involves several methodological aspects, and assessment of uncertainties received particular attention. ProZES systematically uses the principle of multi-model inference. Models of radiation risk were either newly developed or critically re-evaluated for ProZES, including dedicated models for frequent types of cancer and, for less common diseases, models for groups of functionally similar cancer sites. The low-LET models originate mostly from the study of atomic bomb survivors in Hiroshima and Nagasaki. Risks predicted by these models are adjusted to be applicable to the population of Germany and to different time periods. Adjustment factors for low dose rates and for a reduced risk during the minimum latency time between exposure and cancer are also applied. The development of the methodology and software was initiated and supported by the German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU) taking up advice by the German Commission on Radiological Protection (SSK, Strahlenschutzkommission). These provide the scientific basis to support decision making on compensation claims regarding malignancies following occupational exposure to radiation in Germany.

Trauma, Contingency, and The Psychoanalytic Zero

ABSTRACT This article begins the examination of suffering and its relation to the experience of being human. Trauma is neither an experience nor an actual event, but the beginning of the “human” condition. The argument is illustrated through interwoven narratives of transgenerational trauma that arose in the psychoanalytic treatment of a traumatized patient whose parents were atomic bomb survivors in Hiroshima and Nagasaki. It describes the patient’s and analyst’s surrender to the nameless universe in which the division between victim and victimizer is a production of contingency.

Radiation and Risk of Liver, Biliary Tract, and Pancreatic Cancers among Atomic Bomb Survivors in Hiroshima and Nagasaki: 1958-2009.

The Life Span Study (LSS) of atomic bomb survivors has consistently demonstrated significant excess radiation-related risks of liver cancer since the first cancer incidence report. Here, we present updated information on radiation risks of liver, biliary tract and pancreatic cancers based on 11 additional years of follow-up since the last report, from 1958 to 2009. The current analyses used improved individual radiation doses and accounted for the effects of alcohol consumption, smoking and body mass index. The study participants included 105,444 LSS participants with known individual radiation dose and no known history of cancer at the start of follow-up. Cases were the first primary incident cancers of the liver (including intrahepatic bile duct), biliary tract (gallbladder and other and unspecified parts of biliary tract) or pancreas identified through linkage with population-based cancer registries in Hiroshima and Nagasaki. Poisson regression methods were used to estimate excess relative risks (ERRs) and excess absolute risks (EARs) associated with DS02R1 doses for liver (liver and biliary tract cancers) or pancreas (pancreatic cancer). We identified 2,016 incident liver cancer cases during the follow-up period. Radiation dose was significantly associated with liver cancer risk (ERR per Gy: 0.53, 95% CI: 0.23 to 0.89; EAR per 10,000 person-year Gy: 5.32, 95% CI: 2.49 to 8.51). There was no evidence for curvature in the radiation dose response (P=0.344). ERRs by age-at-exposure categories were significantly increased among those who were exposed at 0-9, 10-19 and 20-29 years, but not significantly increased after age 30 years, although there was no statistical evidence of heterogeneity in these ERRs (P = 0.378). The radiation ERRs were not affected by adjustment for smoking, alcohol consumption or body mass index. As in previously reported studies, radiation dose was not associated with risk of biliary tract cancer (ERR per Gy: -0.02, 95% CI: -0.25 to 0.30). Radiation dose was associated with a nonsignificant increase in pancreatic cancer risk (ERR per Gy: 0.38, 95% CI: <0 to 0.83). The increased risk was statistically significant among women (ERR per Gy: 0.70, 95% CI: 0.12 to 1.45), but not among men.

Association between radiation, glaucoma subtype, and retinal vessel diameter in atomic bomb survivors

We examined the relationship between glaucoma subtype and retinal vascular caliber as markers of ocular circulation. Subjects were Japanese atomic bomb survivors in Hiroshima and Nagasaki. After a screening examination, potential cases were subjected to further definitive examination. The diameters of central retinal artery and vein equivalents (CRAE and CRVE) on digitized retinal photographs were measured using an established method. Generalized linear regression analyses were used to examine the associations among vessel diameters, radiation exposure, and prevalence of glaucoma subtypes among the study subjects. We identified 196 cases of glaucoma (12%) based on optic disc appearance, perimetry results, and other ocular findings. The main subtypes were primary angle-closure glaucoma, primary open-angle glaucoma and normal-tension glaucoma (NTG). NTG was the dominant subtype (78%). NTG was negatively associated with CRAE and CRVE, and positively associated with radiation dose. CRVE was negatively associated with radiation dose and the association was unclear for CRAE. The smaller retinal vessel caliber in NTG patients than in subjects without glaucoma may indicate an association between ocular blood flow and the pathogenesis of NTG. However, significant relationships among vessel calibers, NTG and radiation exposure were not clear.

Influence of polypharmacy on heart rate variability in older adults at the Hiroshima Atomic Bomb Survivors Recuperation Research Center, Japan.

BackgroundMany studies have identified the risk of polypharmacy, but physiological evidence and methods of evaluation in these studies were poor. The relationship between polypharmacy and heart rate variability in older adults remains unclear. We investigated the relationship between polypharmacy in older adults, including atomic bomb survivors, and heart rate variability.MethodsWe surveyed 56 older adults who did not need nursing care assistance in the Hiroshima Atomic Bomb Survivors Recuperation Center. Chronic diseases, types of medication, and lifestyle were assessed, and heart rate variability at rest was measured. We calculated heart rate variability indices including standard deviation of normal-to-normal RR intervals (SDNN), total power (TP), and very low frequency (VLF) and analyzed the relationship between the number of daily medication types and heart rate variability indices in older adults. The differences in heart rate variability indices were analyzed using six medications as a cut-off point.ResultsParticipants included 36 atomic bomb survivors and 20 non-atomic bomb survivors. The mean number of medication types was 3.6±3.4 (mean±standard deviation). SDNN, TP, and VLF decreased with an increased number of medications in all participants (P<0.01). When the standard of polypharmacy was set to more than six types of medications, SDNN, TP, and VLF were significantly lower in older adults who took six or more medications. Additionally, the mean number of medication types among atomic bomb survivors was higher than that of non-atomic bomb survivors (P = 0.008). The SDNN was significantly lower when atomic bomb survivors took six or more medications (P<0.001).ConclusionsWe found that a lower heart rate variability in older adults, including atomic bomb survivors, is associated with polypharmacy. We showed physiological evidence of the influence of polypharmacy, which may be important for the healthy life expectancy and prognosis in older adults.

Evidence of a Dose Threshold for Radiation-Induced Leukemia.

In 1958, Neil Wald presented data on the incidence of leukemia among the Hiroshima atomic bomb survivors. These data, which suggested a dose–response threshold for radiation-induced leukemia, were included in the first UNSCEAR report (1958). However, this evidence of a threshold was not recognized. It was obfuscated and concealed. In 2010, Zbigniew Jaworowski identified these data as evidence of radiation hormesis. A letter to the editor in 2014 and 2 articles in 2014 and 2015 presented a graph of these UNSCEAR 1958 data, which revealed a threshold at about 500 mSv. Since the blood-forming stem cells of bone marrow are more radiosensitive than most other cell types, it is reasonable to expect thresholds for inducing other types of cancer by ionizing radiation—their thresholds are likely higher than 500 mSv. A careful examination of the Wald data reveals the suprisingly low incidence of radiogenic leukemia, only 0.5% of the survivors who were in the high radiation zone. Many articles on radiation risk have been published since 2015 by other authors, but none makes reference to this evidence of a threshold, either to challenge or endorse it. In this commentary, the author addresses the comments from a colleague.

The impact of radiation on the development of lung cancer

Environment factors such as radiation play an important role in the incidence of lung cancer. In spite of substantial efforts in experimental study and mathematical modeling, it is still a significant challenge to estimate lung cancer risk from radiation. To address this issue, we propose a stochastic model to investigate the impact of radiation on the development of lung cancer. The proposed three-stage model with clonal expansion is used to match the data of the male and female patients in the Osaka Cancer Registry (OCR) and Life Span Study (LSS) cohort of atomic bomb survivors in Hiroshima and Nagasaki. Our results indicate that the major effect of radiation on the development of lung cancer is to induce gene mutations for both male and female patients. In particular, for male patients, radiation affects the mutation in normal cells and the transformation from premalignant cells to malignant ones. However, radiation for female patients increases the mutation rates of the first two mutations in the stochastic model. The established relationship between parameters and radiation will provide insightful prediction for the lung cancer incidence in the radiation exposure.

The management of survivors’ guilt through the construction of a favorable self in Hiroshima survivor narratives

This study examines how Hiroshima atomic bomb survivors linguistically construct favorable selves – that is, selves that they want to present to others – in stories about events where they may feel survivors’ guilt. While discourse analysts started studying Holocaust narratives in the past decade, the field has not yet investigated narratives from Hiroshima survivors, nor has guilt been extensively investigated linguistically. In narrating those episodes where guilt can be attributed, Hiroshima survivors use various prosodic and syntactic devices to maintain their favorable selves by describing their powerlessness in a chaotic situation. Focusing on the telling of the same experience by three different survivors, the analysis reveals that narrators use various linguistic strategies to protect their positions as moral persons. The study contributes to a better understanding of the linguistic management of emotion, especially survivors’ guilt. Furthermore, linguistic examination of Hiroshima stories brings a discourse perspective to the study of global tragedies.

Solid Cancer Incidence among the Life Span Study of Atomic Bomb Survivors: 1958-2009.

This is the third analysis of solid cancer incidence among the Life Span Study (LSS) cohort of atomic bomb survivors in Hiroshima and Nagasaki, adding eleven years of follow-up data since the previously reported analysis. For this analysis, several changes and improvements were implemented, including updated dose estimates (DS02R1) and adjustment for smoking. Here, we focus on all solid cancers in aggregate. The eligible cohort included 105,444 subjects who were alive and had no known history of cancer at the start of follow-up. A total of 80,205 subjects had individual dose estimates and 25,239 were not in either city at the time of the bombings. The follow-up period was 1958-2009, providing 3,079,484 person-years of follow-up. Cases were identified by linkage with population-based Hiroshima and Nagasaki Cancer Registries. Poisson regression methods were used to elucidate the nature of the radiation-associated risks per Gy of weighted absorbed colon dose using both excess relative risk (ERR) and excess absolute risk (EAR) models adjusted for smoking. Risk estimates were reported for a person exposed at age 30 years with attained age of 70 years. In this study, 22,538 incident first primary solid cancer cases were identified, of which 992 were associated with radiation exposure. There were 5,918 cases (26%) that occurred in the 11 years (1999-2009) since the previously reported study. For females, the dose response was consistent with linearity with an estimated ERR of 0.64 per Gy (95% CI: 0.52 to 0.77). For males, significant upward curvature over the full dose range as well as restricted dose ranges was observed and therefore, a linear-quadratic model was used, which resulted in an ERR of 0.20 (95% CI: 0.12 to 0.28) at 1 Gy and an ERR of 0.010 (95% CI: -0.0003 to 0.021) at 0.1 Gy. The shape of the ERR dose response was significantly different among males and females (P = 0.02). While there was a significant decrease in the ERR with increasing attained age, this decrease was more rapid in males compared to females. The lowest dose range that showed a statistically significant dose response using the sex-averaged, linear ERR model was 0-100 mGy (P = 0.038). In conclusion, this analysis demonstrates that solid cancer risks remain elevated more than 60 years after exposure. Sex-averaged upward curvature was observed in the dose response independent of adjustment for smoking. Findings from the current analysis regarding the dose-response shape were not fully consistent with those previously reported, raising unresolved questions. At this time, uncertainties in the shape of the dose response preclude definitive conclusions to confidently guide radiation protection policies. Upcoming results from a series of analyses focusing on the radiation risks for specific organs or organ families, as well as continued follow-up are needed to fully understand the nature of radiation-related cancer risk and its public health significance. Data and analysis scripts are available for download at: http://www.rerf.or.jp .