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      Radiation-associated circulatory disease mortality in a pooled analysis of 77,275 patients from the Massachusetts and Canadian tuberculosis fluoroscopy cohorts

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          Abstract

          High-dose ionising radiation is associated with circulatory disease. Risks associated with lower-dose (<0.5 Gy) exposures remain unclear, with little information on risk modification by age at exposure, years since exposure or dose-rate. Tuberculosis patients in Canada and Massachusetts received multiple diagnostic x-ray fluoroscopic exposures, over a wide range of ages, many at doses <0.5 Gy. We evaluated risks of circulatory-disease mortality associated with <0.5 Gy radiation exposure in a pooled cohort of 63,707 patients in Canada and 13,568 patients in Massachusetts. Under 0.5 Gy there are increasing trends for all circulatory disease ( n = 10,209; excess relative risk/Gy = 0.246; 95% CI 0.036, 0.469; p = 0.021) and for ischaemic heart disease ( n = 6410; excess relative risk/Gy = 0.267; 95% CI 0.003, 0.552; p = 0.048). All circulatory-disease and ischaemic-heart-disease risk reduces with increasing time since exposure ( p < 0.005). Over the entire dose range, there are negative mortality dose trends for all circulatory disease ( p = 0.014) and ischaemic heart disease ( p = 0.003), possibly due to competing causes of death over this dose interval.These results confirm and extend earlier findings and strengthen the evidence for circulatory-disease mortality radiation risk at doses <0.5 Gy. The limited information on well-known lifestyle/medical risk factors for circulatory disease implies that confounding of the dose trend cannot be entirely excluded.

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          A Proportional Hazards Model for the Subdistribution of a Competing Risk

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            Radiation exposure and circulatory disease risk: Hiroshima and Nagasaki atomic bomb survivor data, 1950-2003

            Objective To investigate the degree to which ionising radiation confers risk of mortality from heart disease and stroke. Design Prospective cohort study with more than 50 years of follow-up. Setting Atomic bomb survivors in Hiroshima and Nagasaki, Japan. Participants 86 611 Life Span Study cohort members with individually estimated radiation doses from 0 to >3 Gy (86% received <0.2 Gy). Main outcome measures Mortality from stroke or heart disease as the underlying cause of death and dose-response relations with atomic bomb radiation. Results About 9600 participants died of stroke and 8400 died of heart disease between 1950 and 2003. For stroke, the estimated excess relative risk per gray was 9% (95% confidence interval 1% to 17%, P=0.02) on the basis of a linear dose-response model, but an indication of possible upward curvature suggested relatively little risk at low doses. For heart disease, the estimated excess relative risk per gray was 14% (6% to 23%, P<0.001); a linear model provided the best fit, suggesting excess risk even at lower doses. However, the dose-response effect over the restricted dose range of 0 to 0.5 Gy was not significant. Prospective data on smoking, alcohol intake, education, occupation, obesity, and diabetes had almost no impact on the radiation risk estimates for either stroke or heart disease, and misdiagnosis of cancers as circulatory diseases could not account for the associations seen. Conclusion Doses above 0.5 Gy are associated with an elevated risk of both stroke and heart disease, but the degree of risk at lower doses is unclear. Stroke and heart disease together account for about one third as many radiation associated excess deaths as do cancers among atomic bomb survivors.
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              Cause-specific mortality in long-term survivors of breast cancer who participated in trials of radiotherapy.

              To examine long-term cause-specific mortality in patients irradiated for breast cancer as part of a randomized clinical trial. We studied all available information from randomized trials initiated before 1975 in which radiotherapy was the randomized option and surgery was the same for both treatment arms. Eight such trials were identified. The increased all-cause mortality rate in 10-year survivors previously reported is no longer significant, although a numerical difference in favor of non-irradiated patients remains. This result was strongly influenced by the earliest trials, and more recent trials have found a nonsignificant net benefit in overall mortality associated with radiation therapy. An excess of cardiac deaths was apparent in both early and more recent trials (P < .001), but this was offset by a reduced number of deaths due to breast cancer, especially in more recent trials. The reduction of breast cancer deaths suggests that radiation therapy may have a value beyond the clearly established improvements obtainable for local control. Use of techniques that minimize cardiac dose is important in reducing the risks of adjuvant radiotherapy, especially in good-prognosis patients.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                13 March 2017
                2017
                : 7
                : 44147
                Affiliations
                [1 ]Radiation Epidemiology Branch, National Cancer Institute , Bethesda, MD 20892-9778, USA
                [2 ]Department of Epidemiology and Biostatistics, School of Medicine, University of California San Francisco , San Francisco, CA, USA
                [3 ]Radiation Epidemiology Branch, National Cancer Institute , Bethesda, MD 20892-9778, USA
                Author notes
                Article
                srep44147
                10.1038/srep44147
                5347030
                28287147
                eab4a410-89a9-47ef-ad04-7fa8cd7b9d4e
                Copyright © 2017, The Author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 26 October 2016
                : 03 February 2017
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