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Takahashi I.,Radiation Effects Research Foundation RERF
Journal of radiological protection : official journal of the Society for Radiological Protection | Year: 2013

Two longitudinal cohort studies of Japanese atomic bomb survivors-the life span study (LSS) and the adult health study (AHS)-from the Radiation Effects Research Foundation (RERF) indicate that total body irradiation doses less than 1 Gy are associated with an increased risk of cardiovascular disease (CVD), but several questions about this association remain.In particular, the diversity of heart disease subtypes and the high prevalence of other risk factors complicate the estimates of radiation effects. Subtype-specific analyses with more reliable diagnostic criteria and measurement techniques are needed. The radiation effects on CVD risk are probably tissue-reaction (deterministic) effects, so the dose-response relationships for various subtypes of CVD may be nonlinear and therefore should be explored with several types of statistical models.Subpopulations at high risk need to be identified because effects at lower radiation doses may occur primarily in these susceptible subpopulations. Whether other CVD risk factors modify radiation effects also needs to be determined. Finally, background rates for various subtypes of CVD have historically differed substantially between Japanese and Western populations, so the generalisability to other populations needs to be examined.Cardiovascular disease mechanisms and manifestations may differ between high-dose local irradiation and low-dose total body irradiation (TBI)-microvascular damage and altered metabolism from low-dose TBI, but coronary artery atherosclerosis and thrombotic myocardial infarcts at high localised doses. For TBI, doses to organs other than the heart may be important in pathogenesis of CVD, so data on renal and liver disorders, plaque instability, microvascular damage, metabolic disorders, hypertension and various CVD biomarkers and risk factors are needed. Epidemiological, clinical and experimental studies at doses of less than 1 Gy are necessary to clarify the effects of radiation on CVD risk. Source

Ruhm W.,Helmholtz Center for Environmental Research | Woloschak G.E.,Northwestern University | Shore R.E.,Radiation Effects Research Foundation RERF | Azizova T.V.,Southern Urals Biophysics Institute SUBI | And 12 more authors.
Radiation and Environmental Biophysics | Year: 2015

The biological effects on humans of low-dose and low-dose-rate exposures to ionizing radiation have always been of major interest. The most recent concept as suggested by the International Commission on Radiological Protection (ICRP) is to extrapolate existing epidemiological data at high doses and dose rates down to low doses and low dose rates relevant to radiological protection, using the so-called dose and dose-rate effectiveness factor (DDREF). The present paper summarizes what was presented and discussed by experts from ICRP and Japan at a dedicated workshop on this topic held in May 2015 in Kyoto, Japan. This paper describes the historical development of the DDREF concept in light of emerging scientific evidence on dose and dose-rate effects, summarizes the conclusions recently drawn by a number of international organizations (e.g., BEIR VII, ICRP, SSK, UNSCEAR, and WHO), mentions current scientific efforts to obtain more data on low-dose and low-dose-rate effects at molecular, cellular, animal and human levels, and discusses future options that could be useful to improve and optimize the DDREF concept for the purpose of radiological protection. © 2015 Springer-Verlag Berlin Heidelberg Source

Adams M.J.,University of Rochester | Grant E.J.,Radiation Effects Research Foundation RERF | Kodama K.,Radiation Effects Research Foundation RERF | Shimizu Y.,Radiation Effects Research Foundation RERF | And 4 more authors.
Radiation Research | Year: 2012

Whole-body and thoracic ionizing radiation exposure are associated with increased cardiovascular disease (CVD) risk. In atomic bomb survivors, radiation dose is also associated with increased hypertension incidence, suggesting that radiation dose may be associated with chronic renal failure (CRF), thus explaining part of the mechanism for increased CVD. Multivariate Poisson regression was used to evaluate the association of radiation dose with various definitions of chronic kidney disease (CKD) mortality in the Life Span Study (LSS) of atomic bomb survivors. A secondary analysis was performed using a subsample for whom self-reported information on hypertension and diabetes, the two biggest risk factors for CRF, had been collected. We found a significant association between radiation dose and only our broadest definition of CRF among the full cohort. A quadratic dose excess relative risk model [ERR/Gy 2 = 0.091 (95% CI: 0.05, 0.198)] fit minimally better than a linear model. Within the subsample, association was also observed only with the broadest CRF definition [ERR/Gy 2 = 0.15 (95% CI: 0.02, 0.32)]. Adjustment for hypertension and diabetes improved model fit but did not substantially change the ERR/Gy 2 estimate, which was 0.17 (95% CI: 0.04, 0.35). We found a significant quadratic dose relationship between radiation dose and possible chronic renal disease mortality that is similar in shape to that observed between radiation and incidence of hypertension in this population. Our results suggest that renal dysfunction could be part of the mechanism causing increased CVD risk after whole-body irradiation, a hypothesis that deserves further study. © 2012 by Radiation Research Society. All rights of reproduction in any form reserved. Source

Kiuchi Y.,Hiroshima University | Yokoyama T.,Hiroshima University | Takamatsu M.,Hiroshima University | Tsuiki E.,Nagasaki University | And 12 more authors.
Radiation Research | Year: 2013

Radiation has been associated with increases in noncancerous diseases. An effect of low-dose radiation on the prevalence of clinically detected glaucoma has not been previously reported. We therefore investigated the prevalence of glaucoma in A-bomb survivors and its possible association with radiation dose. A total of 1,589 people who participated in the clinical examination program for A-bomb survivors at the Radiation Effects Research Foundation (RERF) between October 2006 and September 2008 and who had reconstructed radiation doses, were recruited into this cross-sectional screening study. The prevalence of glaucoma and its dose-response relationship to A-bomb radiation were measured. Each subject underwent an initial screening consisting of an interview and ophthalmological examination. Questionable cases with any indication of ocular disease, including glaucoma, were referred to local hospitals for more comprehensive evaluation. A diagnosis of glaucoma was made based on specific optic disc appearance, perimetric results and other ocular findings. Of 1,589 eligible people, we detected 284 (17.9%) cases of glaucoma overall, including 36 (2.3%) cases of primary open-angle glaucoma with intraocular pressure levels greater than 21 mmHg, 226 (14.2%) cases of normal-tension glaucoma and 25 (1.6%) cases of primary angle-closure glaucoma. Seven glaucoma risk factors were examined as potential confounders but only two needed to be included in the final model. Binary regression using a generalized estimating equation method, with adjustment for gender, age, city, cataract surgery or diabetes mellitus, revealed an odds ratio at 1 Gy of 1.31 (95% confidence interval 1.11-1.53, P = 0.001) in the case of normal-tension glaucoma, but no association for other types of glaucoma. The prevalence of normal-tension glaucoma may increase with A-bomb radiation dose, but uncertainties associated with nonparticipation (59% participation) suggest caution in the interpretation of these results until they are confirmed by other studies. © 2013 by Radiation Research Society. Source

Kodama K.,Radiation Effects Research Foundation RERF | Ozasa K.,Radiation Effects Research Foundation RERF | Okubo T.,Radiation Effects Research Foundation RERF
Journal of Radiological Protection | Year: 2012

With the aim of accurately assessing the effects of radiation exposure in the Japanese atomic-bomb survivors, the Radiation Effects Research Foundation has, over several decades, conducted studies of the Life Span Study (LSS) cohort, comprising 93 000 atomic-bomb survivors and 27 000 controls. Solid cancer: the recent report on solid cancer incidence found that at age 70 years following exposure at age 30 years, solid cancer rates increase by about 35% Gy -1 for men and 58%Gy -1 for women. Age-at-exposure is an important risk modifier. In the case of lung cancer, cigarette smoking has been found to be an important risk modifier. Radiation has similar effects on first-primary and second-primary cancer risks. Finally, radiation-associated increases in cancer rates appear to persist throughout life. Leukaemia: the recent report on leukaemia mortality suggests that radiation effects on leukaemia mortality persisted for more than 50 years. Moreover, significant dose-response for myelodysplastic syndrome was observed in Nagasaki LSS members even 40-60 years after radiation exposure. Future perspective: given the continuing solid cancer increase in the survivor population, the LSS will likely continue to provide important new information on radiation exposure and solid cancer risks for another 15-20 years, especially for those exposed at a young age. © 2012 IOP Publishing Ltd. Source

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