Cohort Of Atomic Bomb Survivors Research Articles

The Effect of Prostate-Specific Antigen (PSA) Test on Radiation Risk Estimate for Prostate Cancer Incidence among Atomic-Bomb Survivors.

Following our previous report on the radiation dose-response for prostate cancer incidence rates in the Life Span Study (LSS) cohort of atomic bomb survivors, we reevaluated the radiation-related risk adjusting for differences in baseline cancer incidence rates among three subsets of the LSS cohort defined by the timing of their first participation in biennial health examinations offered to the Adult Health Study (AHS) sub-cohort members and prostate-specific-antigen (PSA) testing status for AHS participants: 1. non-AHS participants, 2. AHS participants before receiving PSA test, and 3. AHS participants after receiving PSA test. We found a 2.9-fold increase in the baseline incidence rates among AHS participants after receiving PSA test. After adjusting for the PSA-testing-status effects on the baseline rates the estimated excess relative risk (ERR) per Gy was 0.54 (95% CI: 0.15, 1.05), which was almost identical to the previously reported unadjusted ERR estimate (0.57, 95% CI: 0.21, 1.00). The current results confirmed that, while the PSA testing among AHS participants increased the baseline incidence rates, it did not impact the radiation risk estimate, strengthening the previously reported dose-response relationship for prostate cancer incidence in the LSS. As the use of PSA tests continue in screening and medical settings, analyses of possible effects of PSA testing should be an important aspect of future epidemiological studies of the association between radiation exposure and prostate cancer.

Breast cancer incidence risk in accidentally exposed persons of the Southern Urals

The objective of the paper is to assess the breast cancer incidence risk in the Ural cohort of accidentally exposed population. The cohort of people exposed in the Southern Urals on the Techa River and in the East Ural Radioactive Trace was created in 2018. This is the first time that breast cancer risk analysis in women in this cohort is being carried out. Over the period from 1956 to 2018, 337breast cancer cases and 741,533person-years at risk were reported in the female subcohort in the incidence catchment area. Mean accumulated dose to the mammary gland, calculated using the TRDS-2016 dosimetry system, was 46 mGy, the maximum dose was 1 Gy. Regression analysis was performed using the EPICURE software package. Statistical significance with 95% probability was assessed by the maximum likelihood method. As a result of the analysis, a statistically significant linear dependence of breast cancer parameters on the dose was obtained. Excess relative risk for the follow-up period from 1956 through 2018 for members of the female subcohort with a 5-year latency period was 2.39 / Gy. The paper also discusses the impact of available for analyses non-radiation factors on both baseline rates of breast cancer incidence and those associated with radiation exposure. These results do not contradict those obtained in the previous study in the Techa River Cohort separately, and in the Japanese L SS cohort of atomic bomb survivors.

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.

Incidence of lymphoid neoplasms among atomic bomb survivors by histological subtype, 1950 to 1994

AbstractEpidemiological data have provided limited and inconsistent evidence on the relationship between radiation exposure and lymphoid neoplasms. We classified 553 lymphoid neoplasm cases diagnosed between 1950 and 1994 in the Life Span Study cohort of atomic bomb survivors into World Health Organization subtypes. Mature B-cell neoplasms represented 58%, mature T-cell and natural killer (NK)-cell neoplasms 20%, precursor cell neoplasms 5%, and Hodgkin lymphoma (HL) 3%, with the remaining 15% classified as non-Hodgkin lymphoid (NHL) neoplasms or lymphoid neoplasms not otherwise specified. We used Poisson regression methods to assess the relationship between radiation exposure and the more common subtypes. As in earlier reports, a significant dose response for NHL neoplasms as a group was seen for males but not females. However, subtype analyses showed that radiation dose was strongly associated with increased precursor cell neoplasms rates, with an estimated excess relative risk per Gy of 16 (95% Confidence interval: 7.0, >533) at age 50. The current data based primarily of tissue-based diagnoses suggest that the association between radiation dose and lymphoid neoplasms as a group is largely driven by the radiation effect on precursor cell neoplasms while presenting no evidence of a radiation dose response for major categories of mature cell neoplasms, either B- or T-/NK-cell, or more specific disease entities (diffuse large B-cell lymphoma, plasma cell myeloma, adult T-cell leukemia/lymphoma) or HL.

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.

Cancer risk of CT scan in COVID-19: Resolving the dilemma.

Cancer risk of CT scan in COVID-19: Resolving the dilemma.

Modeling low-dose radiation-induced acute myeloid leukemia in male CBA/H mice

The effect of low-dose ionizing radiation exposure on leukemia incidence remains poorly understood. Possible dose-response curves for various forms of leukemia are largely based on cohorts of atomic bomb survivors. Animal studies can contribute to an improved understanding of radiation-induced acute myeloid leukemia (rAML) in humans. In male CBA/H mice, incidence of rAML can be described by a two-hit model involving a radiation-induced deletion with Sfpi1 gene copy loss and a point mutation in the remaining Sfpi1 allele. In the present study (historical) mouse data were used and these processes were translated into a mathematical model to study photon-induced low-dose AML incidence in male CBA/H mice following acute exposure. Numerical model solutions for low-dose rAML incidence and diagnosis times could respectively be approximated with a model linear-quadratic in radiation dose and a normal cumulative distribution function. Interestingly, the low-dose incidence was found to be proportional to the modeled number of cells carrying the Sfpi1 deletion present per mouse following exposure. After making only model-derived high-dose rAML estimates available to extrapolate from, the linear-quadratic model could be used to approximate low-dose rAML incidence calculated with our mouse model. The accuracy in estimating low-dose rAML incidence when extrapolating from a linear model using a low-dose effectiveness factor was found to depend on whether a data transformation was used in the curve fitting procedure.

Risk of Prostate Cancer Incidence among Atomic Bomb Survivors: 1958-2009.

Epidemiological evidence for a radiation effect on prostate cancer risk has been inconsistent and largely indicative of no or little effect. Here we studied prostate cancer incidence among males of the Life Span Study cohort of atomic bomb survivors in a follow-up from 1958 to 2009, eleven years more than was previously reported. During this period there were 851 incident cases of prostate cancer among 41,544 male subjects, doubling the total number of cases in the cohort. More than 50% of the cases were diagnosed among those who were less than 20 years of age at the time of the bombings and who were at, or near, the ages of heightened prostate cancer risks during the last decade of follow-up. In analyses of the radiation dose response using Poisson regression methods, we used a baseline-rate model that allowed for calendar period effects corresponding to the emergence of prostate-specific antigen screening in the general population as well as effects of attained age and birth cohort. The model also allowed for markedly increased baseline rates among the Adult Health Study participants between 2005 and 2009, a period during which a prostate-specific antigen test was included in Adult Health Study biennial health examinations. We found a significant linear dose response with an estimated excess relative risk (ERR) per Gy of 0.57 (95% CI: 0.21, 1.00, P = 0.001). An estimated 40 of the observed cases were attributed to radiation exposure from the bombings. There was a suggestion of the ERR decreasing with increasing age at exposure (P = 0.09). We found no indication of effects of smoking, alcohol consumption and body mass index on the baseline risk of prostate cancer. The observed dose response strengthens the evidence of a radiation effect on the risk of prostate cancer incidence in the atomic bomb survivors.

Solid cancer incidence risk in in the Ural cohort of the accidentally exposed population: 1956–2017

To date, the study of the effects of chronic exposure of the South Ural population has been carried out in two separate cohorts – in the Techa River Cohort and in the East Urals Radioactive Trace Cohort. In 2019, the Ural cohort of accidentally exposed population was formed. It included the population exposed in two radiation situations in the Southern Urals in the 1950s. The number of the combined cohort for the cancer incidence analysis was about 60 thousand people, the follow-up period was extended to 2017, the number of solid cancers was 4537, and the number of person-years was 1283267, which is 3 times more than when analyzing the effects of exposure in each of the two radiation situations separately. In the incidence analysis of all solid cancer types, we used the dose accumulated in the walls of the stomach, which corresponds to the dose accumulated in most organs and tissues with the exception of bone tissue and red bone marrow. The mean dose to the stomach accumulated over the entire follow-up period for cohort members was 38 mGy, the maximum -1.13 Gy. The paper presents the first results of solid cancer incidence risk analysis in the combined cohort, which show a statistically significant dose dependence of the incidence in case of chronic exposure in the range of low and medium doses. The sex and age-averaged excess relative risk value of 0.075/100 mGy (the 95% confidence interval is 0.039–0.113) is comparable to that obtained in the studies of the Japanese cohort of atomic bomb survivors. The statistically significant excess relative risk value of 0.047/100 mGy, obtained separately for men, is in good agreement with that in professional cohorts where men prevail – in the cohort of the Chernobyl NPP accident clean-up workers and in the cohort of professional workers in the three countries (UK, France, USA). The established cohort with a long follow-up period has a great potential for furthermore detailed studies of the effects of radiation and non-radiation factors on public health.

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). The current study is aimed at evaluating the modifying effect of CAG on radiation risk of noncardia gastric cancer by histological type, by reanalyzing data from a nested case-control study conducted within the longitudinal clinical cohort of atomic bomb survivors. The analysis was restricted to 297 intestinal- or diffuse-type noncardia cases and 873 controls rematched to the cases on gender, age, city, and time and type of serum storage, and countermatched on radiation dose. Multivariable-adjusted relative risks [95% confidence interval (CI)] of noncardia gastric cancer were 3.9 (2.1-7.2) for H. pylori IgG seropositivity with cytotoxin-associated gene A (CagA) IgG low titer, 2.6 (1.9-3.6) for CAG, 1.9 (1.3-2.8) for current smoking, and 1.4 (1.1-1.9) for 1 Gy irradiation. Among subjects without CAG, the relative risk (95% CI) of noncardia gastric cancer at 1 Gy was 2.3 (1.4-3.7), whereas relative risk (95% CI) at 1 Gy was 1.1 (0.8-1.5) among subjects with CAG (for the overall interaction, P = 0.012). By histological type, the risk at 1 Gy was high for diffuse type without CAG, with adjusted relative risk (95% CI) of 3.8 (2.0-7.6), but was not high for diffuse type with CAG or for intestinal-type irrespective of CAG status. The results indicate that radiation exposure is associated with increased risk of diffuse-type noncardia gastric cancer without CAG, and this association exists despite adjustment for H. pylori infection and smoking habit.

Radiation risk of central nervous system tumors in the Life Span Study of atomic bomb survivors, 1958-2009.

Radiation exposure is among the few factors known to be associated with risk of central nervous system (CNS) tumors. However, the patterns of radiation risk by histological type, sex or age are unclear. We evaluated radiation risks of first primary glioma, meningioma, schwannoma, and other or not otherwise specified (other/NOS) tumors in the Life Span Study cohort of atomic bomb survivors. Cases diagnosed between 1958 and 2009 were ascertained through population-based cancer registries in Hiroshima and Nagasaki. To estimate excess relative risk per Gy (ERR/Gy), we fit rate models using Poisson regression methods. There were 285 CNS tumors (67 gliomas, 107 meningiomas, 49 schwannomas, and 64 other/NOS tumors) among 105,444 individuals with radiation dose estimates to the brain contributing 3.1 million person-years of observation. Based on a simple linear model without effect modification, ERR/Gy was 1.67 (95% confidence interval, CI: 0.12 to 5.26) for glioma, 1.82 (95% CI: 0.51 to 4.30) for meningioma, 1.45 (95% CI: - 0.01 to 4.97) for schwannoma, and 1.40 (95% CI: 0.61 to 2.57) for all CNS tumors as a group. For each tumor type, the dose-response was consistent with linearity and appeared to be stronger among males than among females, particularly for meningioma (P = 0.045). There was also evidence that the ERR/Gy for schwannoma decreased with attained age (P = 0.002). More than 60years after the bombings, radiation risks for CNS tumors continue to be elevated. Further follow-up is necessary to characterize the lifetime risks of specific CNS tumors following radiation exposure.

Radiation-Related Risk of Cancers of the Upper Digestive Tract among Japanese Atomic Bomb Survivors.

As a follow-up to the comprehensive work on solid cancer incidence in the Life Span Study (LSS) cohort of atomic bomb survivors between 1958 and 1998, we report here on updated radiation risk estimates for upper digestive tract cancers. In this study, we added 11 years of follow-up (1958-2009), used improved radiation dose estimates, considered effects of smoking and alcohol consumption and performed dose-response analyses by anatomical sub-site. In examining 52 years'worth of data, we ascertained the occurrence of 394 oral cavity/pharyngeal cancers, 486 esophageal cancers and 5,661 stomach cancers among 105,444 subjects. The radiation risk for oral cavity/pharyngeal cancer, other than salivary gland, was elevated but not significantly so. In contrast, salivary gland cancer exhibited a strong linear dose response with excess relative risk (ERR) of 2.54 per Gy [95% confidence interval (CI): 0.69 to 6.1]. Radiation risk decreased considerably with increasing age at time of exposure (-66% per decade, 95% CI: -88% to -32%). The dose response for esophageal cancer was statistically significant under a simple linear, linear-quadratic and quadratic model. Both linear-quadratic and quadratic models described the data better than a simple linear model and, of the two, the quadratic model showed a marginally better fit based on the Akaike Information Criteria. Sex difference in linear ERRs was not statistically significant; however, when the dose-response shape was allowed to vary by sex, statistically significant curvature was found among males, with no evidence of quadratic departure from linearity among females. The risk for stomach cancer increased significantly with dose and there was little evidence for quadratic departure from linearity among either males or females. The sex-averaged ERR at age 70 was 0.33 per Gy (95% CI: 0.20 to 0.47). The ERR decreased significantly (-1.93 power of attained age, 95% CI: -2.94 to -0.82) with increasing attained age, but not with age at exposure, and was higher in females than males (P = 0.02). Our results are largely consistent with the results of prior LSS analyses. Salivary gland, esophageal and stomach cancers continue to show significant increases in risk with radiation dose. Adjustment for lifestyle factors had almost no impact on the radiation effect estimates. Further follow-up of the LSS cohort is important to clarify the nature of radiation effects for upper digestive tract cancers, especially for oral cavity/pharyngeal and esophageal cancers, for which detailed investigation for dose-response shape could not be conducted due to the small number of cases.

Hypertension Incidence Risk in a Cohort of Russian Workers Exposed to Radiation at the Mayak Production Association Over Prolonged Periods.

The study was aimed to assess hypertension incidence risk in a cohort of workers occupationally exposed to ionizing radiation. The cohort included workers of Russian Mayak nuclear enterprise who were employed in 1948 to 1982 and followed up until December 31, 2013 (22 377 workers). All workers were occupationally exposed to external γ-rays and some (76.03%) also to α-particles from internally deposited plutonium. Mean cumulative absorbed liver doses from external γ-rays (mean±SD) were 0.45±0.65 Gy in male and 0.37±0.56 Gy in female, whereas doses from internal α-particles were 0.23±0.65 and 0.44±1.93 Gy in males and females, respectively. An excess relative risk per unit dose was calculated based on Poisson regression analysis and was described as linear and nonlinear trends with radiation dose including adjustments for nonradiation factors via stratifications. As of the end of the follow-up period, 8425 hypertension cases (38% of workers) were verified in the cohort (5745 cases in males [36%] and 2680 cases in females [49%]). Hypertension incidence was found to be significantly linearly associated with cumulative liver absorbed dose from external γ-rays: excess relative risk/Gy=0.14 (95% CI, 0.09-0.20). No significant association of hypertension incidence with cumulative liver absorbed dose from internal α-particles was found: excess relative risk/Gy=-0.01 (95% CI, non-available-0.05). Hypertension incidence risk in the study cohort was higher than that in the Japanese cohort of atomic bomb survivors (AHS [Adult Health Study]) but lower than a corresponding estimate for Chernobyl clean-up workers.

Type 2 diabetes, obesity, and breast cancer risk among Japanese women of the atomic bomb survivor cohort

BackgroundMuch less is known about diabetes than obesity as a predictor of breast cancer incidence and most previous studies have been conducted in white populations. Therefore, this project within the Radiation Effects Research Foundation’s cohort of Japanese atomic bomb survivors aimed to determine the independent contributions of obesity and diabetes to develop breast cancer. MethodsAfter excluding women with unknown A-bomb radiation dose, a radiation dose of ≥100 mGy, a pre-existing history of breast cancer, and missing body mass index (BMI), the analysis included 29,818 women. Breast cancer status and deaths until 2009 were identified from cancer registries and vital records. Cox regression with age as the time metric was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for BMI and diabetes status as time-varying exposures alone and in combination while adjusting for known confounders. ResultsDiabetes prevalence increased from 2.6% to 5.3% and 7.5% from the first to the second and third data collection. During 27.6 ± 12.2 years of follow-up, 703 women had developed breast cancer (mean age of 66.0 ± 12.9 years) and 31 (4.4%) had been diagnosed with diabetes. A diagnosis of diabetes was not significantly associated with breast cancer incidence without (HR 1.12, 95% CI 0.77–1.64) and with BMI (HR 1.01, 95% CI 0.69–1.49) as a covariate. The respective HRs for overweight and obesity were 1.61 (95% CI 1.34–1.93) and 2.04 (95% CI 1.40–2.97). ConclusionsAmong a long-time Japanese cohort, excess body weight but not a diabetes diagnosis was significantly associated with breast cancer risk.

The Linear No-Threshold Model of Low-Dose Radiogenic Cancer: A Failed Fiction.

The linear no-threshold (LNT) model for low-dose, radiogenic cancer has been a fixture of radiation protection and regulatory requirements for decades, but its validity has long been contested. This article finds, yet again, more questionable data and analyses purporting to support the model, this within the “gold-standard” data set for estimating radiation effects in humans. Herein is addressed a number of significant uncertainties in the Radiation Effects Research Foundation’s Life Span Study (LSS) cohort of atomic bomb survivors, especially in its latest update of 2017, showing that the study’s support of the LNT model is not evidence based. We find that its latest 2 analyses of solid cancer incidence ignore biology and do not support the LNT model. Additionally, we identify data inconsistencies and missing causalities in the LSS data and analyses that place reliance on uncertain, imputed data and apparently flawed modeling, further invalidating the LNT model. These observations lead to a most credible conclusion, one supporting a threshold model for the dose–response relationship between low-dose radiation exposure and radiogenic cancer in humans. Based upon these findings and those cited from others, it becomes apparent that the LNT model cannot be scientifically valid.

Incidence of Breast Cancer in the Life Span Study of Atomic Bomb Survivors: 1958-2009.

The importance of reproductive history in breast tissue development and etiology of sporadic breast cancer in females is well established. However, there is limited evidence of factors, other than age, that modify risk of radiation-related breast cancer. In this study, we evaluated breast cancer incidence in the Life Span Study cohort of atomic bomb survivors, adding 11 years of follow-up and incorporating reproductive history data. We used Poisson regression models to describe radiation risks and modifying effects of age and reproductive factors. Among 62,534 females, we identified 1,470 breast cancers between 1958 and 2009. Of 397 new cases diagnosed since 1998, 75% were exposed before age 20. We found a strong linear dose response with excess relative risk (ERR) of 1.12 per Gy [95% confidence interval (CI): 0.73 to 1.59] for females at age 70 after exposure at age 30. The ERR decreased with increasing attained age ( P = 0.007) while excess absolute rate (EAR) increased with attained age up to age 70 ( P < 0.001). Age at menarche was a strong modifier of the radiation effect: for a given dose, both the ERR and EAR decreased with increasing age at menarche ( P = 0.007 and P < 0.001). Also, independently, age-at-exposure effects on ERR and EAR differed before and after menarche ( P = 0.043 and P = 0.015, respectively, relative to log-linear trends), with highest risks for exposures around menarche. Despite the small number of male breast cancers (n = 10), the data continue to suggest a dose response (ERR per Gy = 5.7; 95% CI: 0.3 to 30.8; P = 0.018). Persistently increased risk of female breast cancer after radiation exposure and its modification pattern suggests heightened breast sensitivity during puberty.

Population Density in Hiroshima and Nagasaki Before the Bombings in 1945: Its Measurement and Impact on Radiation Risk Estimates in the Life Span Study of Atomic Bomb Survivors.

In the Life Span Study cohort of atomic bomb survivors, differences in urbanicity between high-dose and low-dose survivors could confound the association between radiation dose and adverse outcomes. We obtained data on the population distribution in Hiroshima and Nagasaki before the 1945 bombings and quantified the impact of adjustment for population density on radiation risk estimates for mortality (1950-2003) and incident solid cancer (1958-2009). Population density ranged from 4,671 to 14,378 people/km2 in the urban region of Hiroshima and 5,748 to 19,149 people/km2 in the urban region of Nagasaki. Radiation risk estimates for solid cancer mortality were attenuated by 5.1% after adjustment for population density, but those for all-cause mortality and incident solid cancer were unchanged. There was no overall association between population density and adverse outcomes, but there was evidence that the association between density and mortality differed according to age at exposure. Among survivors who were 10-14 years of age in 1945, there was a positive association between population density and risk of all-cause mortality (per 5,000-people/km2 increase, relative risk = 1.053, 95% confidence interval: 1.027, 1.079) and solid cancer mortality (per 5,000-people/km2 increase, relative risk = 1.069, 95% confidence interval: 1.025, 1.115). Our results suggest that radiation risk estimates from the Life Span Study are not sensitive to unmeasured confounding by urban-rural differences.

The LSS Cohort of Atomic Bomb Survivors and LNT. Comments on ''Solid Cancer Incidence among the Life Span Study of Atomic Bomb Survivors: 1958-2009" (Radiat Res 2017; 187:513-37) and "Reply to the Comments by Mortazavi and Doss" (Radiat Res 2017; 188:369-71).

The LSS Cohort of Atomic Bomb Survivors and LNT. Comments on ''Solid Cancer Incidence among the Life Span Study of Atomic Bomb Survivors: 1958-2009" (Radiat Res 2017; 187:513-37) and "Reply to the Comments by Mortazavi and Doss" (Radiat Res 2017; 188:369-71).

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.

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 .