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      Radiation Risks of Leukemia, Lymphoma and Multiple Myeloma Incidence in the Mayak Cohort: 1948–2004

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          Abstract

          Incidence of all types of lymphatic and hematopoietic cancers, including Hodgkin’s lymphoma, non-Hodgkin's lymphoma, multiple myeloma, acute and chronic myeloid leukemia (AML and CML respectively), chronic lymphocytic leukemia (CLL) and other forms of leukemia have been studied in a cohort of 22,373 workers employed at the Mayak Production Association (PA) main facilities during 536,126 person-years of follow-up from the start of employment between 1948 and 1982 to the end of 2004. Risk assessment was performed for both external gamma-radiation and internal alpha-exposure of red bone marrow due to incorporated Pu-239 using Mayak Workers Dosimetry System 2008 taking into account non-radiation factors. The incidence of leukemia excluding CLL showed a non-linear dose response relationship for external gamma exposure with exponential effect modifiers based on time since exposure and age at exposure. Among the major subtypes of leukemia, the excess risk of AML was the highest within the first 2–5 years of external exposure (ERR per Gy: 38.40; 90% CI: 13.92–121.4) and decreased substantially thereafter, but the risks remained statistically significant (ERR per Gy: 2.63; 90% CI: 0.07–12.55). In comparison, excess CML first occurred 5 years after exposure and decreased about 10 years after exposure, although the association was not statistically significant (ERR per Gy: 1.39; 90% CI: -0.22–7.32). The study found no evidence of an association between leukemia and occupational exposure to internal plutonium ERR per Gy 2.13; 90% CI: <0–9.45). There was also no indication of any relationship with either external gamma or internal plutonium radiation exposure for either incidence of Hodgkin or non-Hodgkin lymphoma or multiple myeloma.

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          Studies of the mortality of atomic bomb survivors, Report 14, 1950-2003: an overview of cancer and noncancer diseases.

          This is the 14th report in a series of periodic general reports on mortality in the Life Span Study (LSS) cohort of atomic bomb survivors followed by the Radiation Effects Research Foundation to investigate the late health effects of the radiation from the atomic bombs. During the period 1950-2003, 58% of the 86,611 LSS cohort members with DS02 dose estimates have died. The 6 years of additional follow-up since the previous report provide substantially more information at longer periods after radiation exposure (17% more cancer deaths), especially among those under age 10 at exposure (58% more deaths). Poisson regression methods were used to investigate the magnitude of the radiation-associated risks, the shape of the dose response, and effect modification by gender, age at exposure, and attained age. The risk of all causes of death was positively associated with radiation dose. Importantly, for solid cancers the additive radiation risk (i.e., excess cancer cases per 10(4) person-years per Gy) continues to increase throughout life with a linear dose-response relationship. The sex-averaged excess relative risk per Gy was 0.42 [95% confidence interval (CI): 0.32, 0.53] for all solid cancer at age 70 years after exposure at age 30 based on a linear model. The risk increased by about 29% per decade decrease in age at exposure (95% CI: 17%, 41%). The estimated lowest dose range with a significant ERR for all solid cancer was 0 to 0.20 Gy, and a formal dose-threshold analysis indicated no threshold; i.e., zero dose was the best estimate of the threshold. The risk of cancer mortality increased significantly for most major sites, including stomach, lung, liver, colon, breast, gallbladder, esophagus, bladder and ovary, whereas rectum, pancreas, uterus, prostate and kidney parenchyma did not have significantly increased risks. An increased risk of non-neoplastic diseases including the circulatory, respiratory and digestive systems was observed, but whether these are causal relationships requires further investigation. There was no evidence of a radiation effect for infectious or external causes of death.
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            Mortality and cancer incidence following occupational radiation exposure: third analysis of the National Registry for Radiation Workers

            Mortality and cancer incidence were studied in the National Registry for Radiation Workers in, relative to earlier analyses, an enlarged cohort of 174 541 persons, with longer follow-up (to 2001) and, for the first time, cancer registration data. SMRs for all causes and all malignant neoplasms were 81 and 84 respectively, demonstrating a ‘healthy worker effect'. Within the cohort, mortality and incidence from both leukaemia excluding CLL and the grouping of all malignant neoplasms excluding leukaemia increased to a statistically significant extent with increasing radiation dose. Estimates of the trend in risk with dose were similar to those for the Japanese A-bomb survivors, with 90% confidence intervals that excluded both risks more than 2–3 times greater than the A-bomb values and no raised risk. Some evidence of an increasing trend with dose in mortality from all circulatory diseases may, at least partly, be due to confounding by smoking. This analysis provides the most precise estimates to date of mortality and cancer risks following occupational radiation exposure and strengthens the evidence for raised risks from these exposures. The cancer risk estimates are consistent with values used to set radiation protection standards.
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              Cancer mortality risk among workers at the Mayak nuclear complex.

              At present, direct data on risk from protracted or fractionated radiation exposure at low dose rates have been limited largely to studies of populations exposed to low cumulative doses with resulting low statistical power. We evaluated the cancer risks associated with protracted exposure to external whole-body gamma radiation at high cumulative doses (the average dose is 0.8 Gy and the highest doses exceed 10 Gy) in Russian nuclear workers. Cancer deaths in a cohort of about 21,500 nuclear workers who began working at the Mayak complex between 1948 and 1972 were ascertained from death certificates and autopsy reports with follow-up through December 1997. Excess relative risk models were used to estimate solid cancer and leukemia risks associated with external gamma-radiation dose with adjustment for effects of plutonium exposures. Both solid cancer and leukemia death rates increased significantly with increasing gamma-ray dose (P < 0.001). Under a linear dose-response model, the excess relative risk for lung, liver and skeletal cancers as a group (668 deaths) adjusted for plutonium exposure is 0.30 per gray (P < 0.001) and 0.08 per gray (P < 0.001) for all other solid cancers (1062 deaths). The solid cancer dose-response functions appear to be nonlinear, with the excess risk estimates at doses of less than 3 Gy being about twice those predicted by the linear model. Plutonium exposure was associated with increased risks both for lung, liver and skeletal cancers (the sites of primary plutonium deposition) and for other solid cancers as a group. A significant dose response, with no indication of plutonium exposure effects, was found for leukemia. Excess risks for leukemia exhibited a significant dependence on the time since the dose was received. For doses received within 3 to 5 years of death the excess relative risk per gray was estimated to be about 7 (P < 0.001), but this risk was only 0.45 (P = 0.02) for doses received 5 to 45 years prior to death. External gamma-ray exposures significantly increased risks of both solid cancers and leukemia in this large cohort of men and women with occupational radiation exposures. Risks at doses of less than 1 Gy may be slightly lower than those seen for doses arising from acute exposures in the atomic bomb survivors. As dose estimates for the Mayak workers are improved, it should be possible to obtain more precise estimates of solid cancer and leukemia risks from protracted external radiation exposure in this cohort.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                15 September 2016
                2016
                : 11
                : 9
                : e0162710
                Affiliations
                [1 ]Southern Urals Biophysics Institute (SUBI), Ozyorsk, Chelyabinsk Region, Russia
                [2 ]Public Health England (PHE), Centre for Radiation, Chemical and Environmental Hazards (CRCE), Chilton, Oxfordshire, United Kingdom
                Kagoshima University Graduate School of Medical and Dental Sciences, JAPAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: ISK EVL.

                • Data curation: EVL NH.

                • Formal analysis: ISK NH.

                • Investigation: EVL.

                • Methodology: ISK NH.

                • Resources: ISK.

                • Validation: EVL.

                • Writing – original draft: ISK.

                Article
                PONE-D-16-32097
                10.1371/journal.pone.0162710
                5025099
                27631102
                fe34973f-f7c0-4eda-b520-3b9f85053bd7
                © 2016 Kuznetsova et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 11 August 2016
                : 27 August 2016
                Page count
                Figures: 2, Tables: 6, Pages: 14
                Funding
                This work was supported by the European Commission though EC-SOLO project (CP-IP: 249675) under EC SEVENTH FRAMEWORK PROGRAMME THEME: Radiation Protection - Quantification of Risks for Low and Protracted Exposures.
                Categories
                Research Article
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Hematologic Cancers and Related Disorders
                Leukemias
                Medicine and Health Sciences
                Hematology
                Hematologic Cancers and Related Disorders
                Leukemias
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Hematologic Cancers and Related Disorders
                Leukemias
                Lymphoblastic Leukemia
                Chronic Lymphoblastic Leukemia
                Medicine and Health Sciences
                Hematology
                Hematologic Cancers and Related Disorders
                Leukemias
                Lymphoblastic Leukemia
                Chronic Lymphoblastic Leukemia
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Hematologic Cancers and Related Disorders
                Leukemias
                Myeloid Leukemia
                Acute Myeloid Leukemia
                Medicine and Health Sciences
                Hematology
                Hematologic Cancers and Related Disorders
                Leukemias
                Myeloid Leukemia
                Acute Myeloid Leukemia
                Physical Sciences
                Chemistry
                Chemical Elements
                Plutonium
                Biology and Life Sciences
                Physiology
                Immune Physiology
                Bone Marrow
                Medicine and Health Sciences
                Physiology
                Immune Physiology
                Bone Marrow
                Biology and Life Sciences
                Immunology
                Immune System
                Bone Marrow
                Medicine and Health Sciences
                Immunology
                Immune System
                Bone Marrow
                Medicine and Health Sciences
                Hematology
                Plasma Cell Disorders
                Multiple Myeloma
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Hematologic Cancers and Related Disorders
                Lymphomas
                Medicine and Health Sciences
                Hematology
                Hematologic Cancers and Related Disorders
                Lymphomas
                Medicine and Health Sciences
                Diagnostic Medicine
                Cancer Detection and Diagnosis
                Medicine and Health Sciences
                Oncology
                Cancer Detection and Diagnosis
                Custom metadata
                Data are available from the Southern Urals Biophysics Data Access for researches who meet the criteria for access to confidential data.

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