Congenital Malformations and Perinatal Deaths among the Children of Atomic Bomb Survivors: A Reappraisal.
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ABSTRACT:
SUBMITTER: Yamada M
PROVIDER: S-EPMC8561127 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:There have been some concerns about the influence of medical X rays in dose-response analysis of atomic bomb radiation on health outcomes. Among atomic bomb survivors in the Life Span Study, the association between atomic bomb radiation dose and exposures to medical X rays was investigated using questionnaire data collected by a mail survey conducted between 2007-2011, soliciting information on the history of computed tomography (CT) scans, gastrointestinal fluoroscopy, angiography and radiotherapy. Among 12,670 participants, 76% received at least one CT scan; 77%, a fluoroscopic examination; 23%, an angiographic examination; and 8%, radiotherapy. Descriptive and multivariable-adjusted analyses showed that medical X rays were administered in greater frequencies among those who were exposed to an atomic bomb radiation dose of 1.0 Gy or higher, compared to those exposed to lower doses. This is possibly explained by a greater frequency in major chronic diseases such as cancer in the ?1.0 Gy group. The frequency of medical X rays in the groups exposed to 0.005-0.1 Gy or 0.1-1.0 Gy did not differ significantly from those exposed to <0.005 Gy. An analysis of finer dose groups under 1 Gy likewise showed no differences in frequencies of medical X rays. Thus, no evidence of material confounding of atomic bomb effects was found. Among those exposed to atomic bomb doses <1 Gy, doses were not associated with medical radiation exposures. The significant association of doses ?1 Gy with medical radiation exposures likely produces no substantive bias in radiation effect estimates because diagnostic medical X-ray doses are much lower than the atomic bomb doses. Further information on actual medical X-ray doses and on the validity of self-reports of X-ray procedures would strengthen this conclusion.
| S-EPMC6707719 | biostudies-literature
Project description:Background:Ionizing radiation is known to be capable of causing cancer of many organs, but its relationship with uterine cancer has not been well characterized. Methods:We studied incidence of uterine cancer during 1958-2009 among 62?534 female atomic bomb survivors. Using Poisson regression analysis, we fitted excess relative risk (ERR) models to uterine cancer rates adjusted for several lifestyle and reproductive factors. Person-years at risk were also adjusted for the probability of prior hysterectomy, because it could affect the subsequent risk of uterine cancer. We assessed the modifying effect of age and other factors on the radiation risk. For analysis of the modifying effect of age at radiation exposure around menarche, we compared the radiation risk for several exposure-age categories as well as using parametric models. Results:There were 224 uterine corpus cancers and 982 cervical cancers. We found a significant association between radiation dose and risk of corpus cancer (ERR per Gray [ERR/Gy] = 0.73, 95% confidence interval [CI] = 0.03 to 1.87) but not for cervical cancer (ERR/Gy?=?0.00, 95% CI = -0.22 to 0.31). For corpus cancer, we found statistically significant heterogeneity in ERR/Gy by age (P heterogeneity ?=?.001) with elevated risk for women exposed to radiation between ages 11 and 15 years (ERR/Gy?=?4.10, 95% CI?=?1.47 to 8.42) and no indication of a radiation effect for exposures before or after this exposure-age range. Conclusions:The current data suggest that uterine corpus is especially sensitive to the carcinogenic effect of radiation exposure occurring during the mid-pubertal period preceding menarche. There is little evidence for a radiation effect on cervical cancer risk.
| S-EPMC6586771 | biostudies-literature
Project description:Ionizing radiation is a risk factor for myeloid neoplasms including myelodysplastic syndromes (MDS), and atomic bomb survivors have been shown to have a significantly higher risk of MDS. Our previous analyses demonstrated that MDS among these survivors had a significantly higher frequency of complex karyotypes and structural alterations of chromosomes 3, 8, and 11. However, there was no difference in the median survival time between MDS among survivors compared with those of de novo origin. This suggested that a different pathophysiology may underlie the causative genetic aberrations for those among survivors. In this study, we performed genome analyses of MDS among survivors and found that proximally exposed patients had significantly fewer mutations in genes such as TET2 along the DNA methylation pathways, and they had a significantly higher rate of 11q deletions. Among the genes located in the deleted portion of chromosome 11, alterations of ATM were significantly more frequent in proximally exposed group with mutations identified on the remaining allele in 2 out of 5 cases. TP53, which is frequently mutated in therapy-related myeloid neoplasms, was equally affected between proximally and distally exposed patients. These results suggested that the genetic aberration profiles in MDS among atomic bomb survivors differed from those in therapy-related and de novo origin. Considering the role of ATM in DNA damage response after radiation exposure, further studies are warranted to elucidate how 11q deletion and aberrations of ATM contribute to the pathogenesis of MDS after radiation exposure.
| S-EPMC7012461 | biostudies-literature
Project description:One of the largest sources of data on radiation exposure in humans is the study of the atomic bomb survivors at Hiroshima and Nagasaki, Japan performed by the Radiation Effects Research Foundation (RERF). As part of their retrospective dosimetry efforts for the atomic bomb survivors, RERF published two core systems: Dosimetry System 1986 (DS86) and Dosimetry System 2002 (DS02). Due to computing limitations at the time, only three stylized phantoms (an infant, child and adult) were used in DS86 and DS02 to represent the entire Japanese population. In this study, we sought to evaluate the dosimetric differences that should be expected from using an updated and age-expanded phantom series with the survivor cohort. To this end, we developed a new series of hybrid phantoms, based on the Japanese population of 1945, which has greater anatomical realism and improved age resolution over those used by RERF. These phantoms were converted to voxel format and compared to their older counterparts through the calculation of organ dose coefficients using DS02 free-in-air particle fluences at three distances from the bomb hypocenter. From the photon portion of the spectra, organ dose differences of up to nearly 25% are expected between the old and new series, while organ dose differences of up to nearly 70% are expected from the neutron portion. We also compared organ dose coefficients among themselves to determine the accuracy in the use of one organ dose as the epidemiological surrogate to another. Certain organ-surrogate pairs were shown to be inappropriate, such as the use of colon dose for breast risk analyses. Overall, our new series of phantoms provides significant improvements to survivor organ dosimetry, especially to those survivors who were previously misrepresented in body size by their stylized phantom and to those who experienced a highly-directional irradiation field.
| S-EPMC8666129 | biostudies-literature
Project description:While radiation increases the risk of lung cancer among members of the Life Span Study (LSS) cohort of atomic bomb survivors, there are still important questions about the nature of its interaction with smoking, the predominant cause of lung cancer. Among 105,404 LSS subjects, 1,803 primary lung cancer incident cases were identified for the period 1958-1999. Individual smoking history information and the latest radiation dose estimates were used to investigate the joint effects of radiation and smoking on lung cancer rates using Poisson grouped survival regression methods. Relative to never-smokers, lung cancer risks increased with the amount and duration of smoking and decreased with time since quitting smoking at any level of radiation exposure. Models assuming generalized interactions of smoking and radiation fit markedly better than simple additive or multiplicative interaction models. The joint effect appeared to be super-multiplicative for light/moderate smokers, with a rapid increase in excess risk with smoking intensity up to about 10 cigarettes per day, but additive or sub-additive for heavy smokers smoking a pack or more per day, with little indication of any radiation-associated excess risk. The gender-averaged excess relative risk per Gy of lung cancer (at age 70 after radiation exposure at 30) was estimated as 0.59 (95% confidence interval: 0.31-1.00) for nonsmokers with a female : male ratio of 3.1. About one-third of the lung cancer cases in this cohort were estimated to be attributable to smoking while about 7% were associated with radiation. The joint effect of smoking and radiation on lung cancer in the LSS is dependent on smoking intensity and is best described by the generalized interaction model rather than a simple additive or multiplicative model.
| S-EPMC3857029 | biostudies-literature
Project description: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.
| S-EPMC6570769 | biostudies-literature
Project description:A marked increase in leukemia risks was the first and most striking late effect of radiation exposure seen among the Hiroshima and Nagasaki atomic bomb survivors. This article presents analyses of radiation effects on leukemia, lymphoma and multiple myeloma incidence in the Life Span Study cohort of atomic bomb survivors updated 14 years since the last comprehensive report on these malignancies. These analyses make use of tumor- and leukemia-registry based incidence data on 113,011 cohort members with 3.6 million person-years of follow-up from late 1950 through the end of 2001. In addition to a detailed analysis of the excess risk for all leukemias other than chronic lymphocytic leukemia or adult T-cell leukemia (neither of which appear to be radiation-related), we present results for the major hematopoietic malignancy types: acute lymphoblastic leukemia, chronic lymphocytic leukemia, acute myeloid leukemia, chronic myeloid leukemia, adult T-cell leukemia, Hodgkin and non-Hodgkin lymphoma and multiple myeloma. Poisson regression methods were used to characterize the shape of the radiation dose-response relationship and, to the extent the data allowed, to investigate variation in the excess risks with gender, attained age, exposure age and time since exposure. In contrast to the previous report that focused on describing excess absolute rates, we considered both excess absolute rate (EAR) and excess relative risk (ERR) models and found that ERR models can often provide equivalent and sometimes more parsimonious descriptions of the excess risk than EAR models. The leukemia results indicated that there was a nonlinear dose response for leukemias other than chronic lymphocytic leukemia or adult T-cell leukemia, which varied markedly with time and age at exposure, with much of the evidence for this nonlinearity arising from the acute myeloid leukemia risks. Although the leukemia excess risks generally declined with attained age or time since exposure, there was evidence that the radiation-associated excess leukemia risks, especially for acute myeloid leukemia, had persisted throughout the follow-up period out to 55 years after the bombings. As in earlier analyses, there was a weak suggestion of a radiation dose response for non-Hodgkin lymphoma among men, with no indication of such an effect among women. There was no evidence of radiation-associated excess risks for either Hodgkin lymphoma or multiple myeloma.
| S-EPMC3875218 | biostudies-literature
Project description:The calculated risk of cancer in humans due to radiation exposure is based primarily on long-term follow-up studies, e.g. the life-span study (LSS) on atomic bomb (A-bomb) survivors in Hiroshima and Nagasaki. Since A-bomb radiation consists of a mixture of ?-rays and neutrons, it is essential that the relative biological effectiveness (RBE) of neutrons is adequately evaluated if a study is to serve as a reference for cancer risk. However, the relatively small neutron component hampered the direct estimation of RBE in LSS data. To circumvent this problem, several strategies have been attempted, including dose-independent constant RBE, dose-dependent variable RBE, and dependence on the degrees of dominance of intermingled ?-rays. By surveying the available literature, we tested the chromosomal RBE of neutrons as the biological endpoint for its equivalence to the microdosimetric quantities obtained using a tissue-equivalent proportional counter (TEPC) in various neutron fields. The radiation weighting factor, or quality factor, Qn, of neutrons as expressed in terms of the energy dependence of the maximum RBE, RBEm, was consistent with that predicted by the TEPC data, indicating that the chromosomally measured RBE was independent of the magnitude of coexisting ?-rays. The obtained neutron RBE, which varied with neutron dose, was confirmed to be the most adequate RBE system in terms of agreement with the cancer incidence in A-bomb survivors, using chromosome aberrations as surrogate markers. With this RBE system, the cancer risk in A-bomb survivors as expressed in unit dose of reference radiation is equally compatible with Hiroshima and Nagasaki cities, and may be potentially applicable in other cases of human radiation exposure.
| S-EPMC5137296 | biostudies-literature
Project description:Primary liver cancer is difficult to diagnose accurately at death, due to metastases from nearby organs and to concomitant diseases, such as chronic hepatitis and cirrhosis. Trends in diagnostic accuracy could affect radiation risk estimates for incident liver cancer by altering background rates or by impacting risk modification by sex and age. We quantified the potential impact of death-certificate inaccuracies on radiation risk estimates for liver cancer in the Life Span Study of atomic bomb survivors. True-positive and false-negative rates were obtained from a previous study that compared death-certificate causes of death with those based on pathological review, from 1958 to 1987. We assumed various scenarios for misclassification rates after 1987. We obtained estimated true positives and estimated false negatives by stratified sampling from binomial distributions with probabilities given by the true-positive and false-negative rates, respectively. Poisson regression methods were applied to highly stratified person-year tables of corrected case counts and accrued person years. During the study period (1958-2009), there were 1,885 cases of liver cancer, which included 383 death-certificate-only (DCO) cases; 1,283 cases with chronic liver disease as the underlying cause of death; and 150 DCO cases of pancreatic cancer among 105,444 study participants. Across the range of scenarios considered, radiation risk estimates based on corrected case counts were attenuated, on average, by 13-30%. Our results indicated that radiation risk estimates for liver cancer were potentially sensitive to death-certificate inaccuracies. Additional data are needed to inform misclassification rates in recent years.
| S-EPMC8015398 | biostudies-literature
Project description:The treatment of asymptomatic patients with congenital pulmonary malformations (CPMs) remains controversial, partially because the relationship between congenital lung malformations and malignancy is still undefined. Change in methylation pattern is a crucial event in human cancer, including lung cancer. We therefore studied all differentially methylated regions (DMRs) in a series of CPMs in an attempt to find methylation anomalies in genes already described in association with malignancy. The DNA extracted from resected congenital lung malformations and control lung tissue was screened using Illumina MethylationEPIC arrays. Comparison between the group of malformed samples or the malformed samples of same histology or each malformed sample and the controls, and between a pleuropulmonary blastoma (PPB) and controls were performed. All differentially methylated regions (DMRs) with an adjusted p value < 0,05 were studied. Every comparison highlighted a number of DMRs closed to genes involved either in cell proliferation or in embryonic development or included in the Cancer Gene Census. Their abnormal methylation had been already described in lung tumors. The presence of methylation abnormalities is suggestive of a correlation between congenital lung malformations and some step of malignant transformation.
2021-05-19 | GSE174625 | GEO