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Objectives To provide direct estimates of risk of cancer after protracted low doses of ionising radiation and to strengthen the scientific basis of radiation protection standards for environmental, occupational, and medical diagnostic exposures. Design Multinational retrospective cohort study of cancer mortality. Setting Cohorts of workers in the nuclear industry in 15 countries. Participants 407 391 workers individually monitored for external radiation with a total follow-up of 5.2 million person years. Main outcome measurements Estimates of excess relative risks per sievert (Sv) of radiation dose for mortality from cancers other than leukaemia and from leukaemia excluding chronic lymphocytic leukaemia, the main causes of death considered by radiation protection authorities. Results The excess relative risk for cancers other than leukaemia was 0.97 per Sv, 95% confidence interval 0.14 to 1.97. Analyses of causes of death related or unrelated to smoking indicate that, although confounding by smoking may be present, it is unlikely to explain all of this increased risk. The excess relative risk for leukaemia excluding chronic lymphocytic leukaemia was 1.93 per Sv ( < 0 to 8.47). On the basis of these estimates, 1-2% of deaths from cancer among workers in this cohort may be attributable to radiation. Conclusions These estimates, from the largest study of nuclear workers ever conducted, are higher than, but statistically compatible with, the risk estimates used for current radiation protection standards. The results suggest that there is a small excess risk of cancer, even at the low doses and dose rates typically received by nuclear workers in this study.

Study queStionIs protracted exposure to low doses of ionising radiation associated with an increased risk of solid cancer?

Summary Background There is much uncertainty about the risks of leukaemia and lymphoma after repeated or protracted low-dose radiation exposure typical of occupational, environmental, and diagnostic medical settings. We quantified associations between protracted low-dose radiation exposures and leukaemia, lymphoma, and multiple myeloma mortality among radiation-monitored adults employed in France, the UK, and the USA. Methods We assembled a cohort of 308 297 radiation-monitored workers employed for at least 1 year by the Atomic Energy Commission, AREVA Nuclear Cycle, or the National Electricity Company in France, the Departments of Energy and Defence in the USA, and nuclear industry employers included in the National Registry for Radiation Workers in the UK. The cohort was followed up for a total of 8·22 million person-years. We ascertained deaths caused by leukaemia, lymphoma, and multiple myeloma. We used Poisson regression to quantify associations between estimated red bone marrow absorbed dose and leukaemia and lymphoma mortality. Findings Doses were accrued at very low rates (mean 1·1 mGy per year, SD 2·6). The excess relative risk of leukaemia mortality (excluding chronic lymphocytic leukaemia) was 2·96 per Gy (90% CI 1·17–5·21; lagged 2 years), most notably because of an association between radiation dose and mortality from chronic myeloid leukaemia (excess relative risk per Gy 10·45, 90% CI 4·48–19·65). Interpretation This study provides strong evidence of positive associations between protracted low-dose radiation exposure and leukaemia. Funding Centers for Disease Control and Prevention, Ministry of Health, Labour and Welfare of Japan, Institut de Radioprotection et de Sûreté Nucléaire, AREVA, Electricité de France, National Institute for Occupational Safety and Health, US Department of Energy, US Department of Health and Human Services, University of North Carolina, Public Health England.

Objective To estimate the risk of breast cancer associated with diagnostic radiation in carriers of BRCA1/2 mutations. Design Retrospective cohort study (GENE-RAD-RISK).Setting Three nationwide studies (GENEPSO, EMBRACE, HEBON) in France, United Kingdom, and the Netherlands, Participants 1993 female carriers of BRCA1/2 mutations recruited in 2006-09.Main outcome measure Risk of breast cancer estimated with a weighted Cox proportional hazards model with a time dependent individually estimated cumulative breast dose, based on nominal estimates of organ dose and frequency of self reported diagnostic procedures. To correct for potential survival bias, the analysis excluded carriers who were diagnosed more than five years before completion of the study questionnaire.Results In carriers of BRCA1/2 mutations any exposure to diagnostic radiation before the age of 30 was associated with an increased risk of ConclusionIn this large European study among carriers of BRCA1/2 mutations, exposure to diagnostic radiation before age 30 was associated with an increased risk of breast cancer at dose levels considerably lower than those at which increases have been found in other cohorts exposed to radiation. The results of this study support the use of non-ionising radiation imaging techniques (such as magnetic resonance imaging) as the main tool for surveillance in young women with BRCA1/2 mutations. IntroductionExposure to ionising radiation is an established risk factor for breast cancer in the general population, with exposures in childhood and adolescence conferring a greater risk than exposure in adulthood. 1 As BRCA1 and BRCA2 are involved in the repair of DNA double strand breaks, 2-6 which can be caused by ionising radiation, it has been hypothesised that carriers of BRCA1/2 mutations might have increased radiosensitivity. Results of the few studies 7-10 conducted so far on diagnostic radiation and risk of breast cancer among carriers have been inconsistent. Explanations for this inconsistency include differences in age at exposure and study limitations such as the investigation of a single type of diagnostic procedure (such as only chest radiography 7 8 or only mammography 9 10 ), a retrospective design with potential recall and/or survival bias, [7][8][9][10] or sometimes relatively small numbers. 8 9 In some countries the screening protocol for BRCA1/2 mutation carriers now recommends the avoidance of mammographic screening before age 30 and advises the use of non-ionising radiation imaging techniques (such as magnetic resonance imaging (MRI)) as the main tool for surveillance at young ages.We report on the BRCA1/2 mutation carrier study arm of the GENE-RAD-RISK project, a large European cohort study designed to examine whether variations in specific DNA repair genes increase the risk of breast cancer associated with radiation. Although the present study has a retrospective design, the association between diagnostic radiation and breast cancer risk in BRCA1/2 mutation carriers is unlikely to be investigated p...

Positive associations between external radiation dose and non-cancer mortality have been found in a number of published studies, primarily of populations exposed to high-dose, high-dose-rate ionizing radiation. The goal of this study was to determine whether external radiation dose was associated with non-cancer mortality in a large pooled cohort of nuclear workers exposed to low-dose radiation accumulated at low dose rates. The cohort comprised 308,297 workers from France, United Kingdom and United States. The average cumulative equivalent dose at a tissue depth of 10 mm [Hp(10)] was 25.2 mSv. In total, 22% of the cohort were deceased by the end of follow-up, with 46,029 deaths attributed to non-cancer outcomes, including 27,848 deaths attributed to circulatory diseases. Poisson regression was used to investigate the relationship between cumulative radiation dose and non-cancer mortality rates. A statistically significant association between radiation dose and all non-cancer causes of death was observed [excess relative risk per sievert (ERR/Sv) = 0.19; 90% CI: 0.07, 0.30]. This was largely driven by the association between radiation dose and mortality due to circulatory diseases (ERR/Sv = 0.22; 90% CI: 0.08, 0.37), with slightly smaller positive, but nonsignificant, point estimates for mortality due to nonmalignant respiratory disease (ERR/Sv = 0.13; 90% CI: −0.17, 0.47) and digestive disease (ERR/Sv = 0.11; 90% CI: −0.36, 0.69). The point estimate for the association between radiation dose and deaths due to external causes of death was nonsignificantly negative (ERR = −0.12; 90% CI: <−0.60, 0.45). Within circulatory disease subtypes, associations with dose were observed for mortality due to cerebrovascular disease (ERR/Sv = 0.50; 90% CI: 0.12, 0.94) and mortality due to ischemic heart disease (ERR/Sv = 0.18; 90% CI: 0.004, 0.36). The estimates of associations between radiation dose and non-cancer mortality are generally consistent with those observed in atomic bomb survivor studies. The findings of this study could be interpreted as providing further evidence that non-cancer disease risks may be increased by external radiation exposure, particularly for ischemic heart disease and cerebrovascular disease. However, heterogeneity in the estimated ERR/Sv was observed, which warrants further investigation. Further follow-up of these cohorts, with the inclusion of internal exposure information and other potential confounders associated with lifestyle factors, may prove informative, as will further work on elucidating the biological mechanisms that might cause these non-cancer effects at low doses.

To provide direct estimates of cancer risk after low-dose protracted exposure to ionizing radiation, a large-scale epidemiological study of nuclear industry workers was conducted in 15 countries. As part of this study, identification and quantification of errors in historical recorded doses was conducted based on a review of dosimetric practices and technologies in participating facilities. The main sources of errors on doses from "high-energy" photons (100-3000 keV) were identified as the response of dosimeters in workplace exposure conditions and historical calibration practices. Errors related to dosimetry technology and radiation fields were quantified to derive period- and facility-specific estimates of bias and uncertainties in recorded doses. This was based on (1) an evaluation of predominant workplace radiation from measurement studies and dosimetry expert assessment and (2) an estimation of the energy and geometry response of dosimeters used historically in study facilities. Coefficients were derived to convert recorded doses to H(p) (10) and organ dose, taking into account different aspects of the calibration procedures. A parametric, lognormal error structure model was developed to describe errors in doses as a function of facility and time period. Doses from other radiation types, particularly neutrons and radionuclide intake, could not be adequately reconstructed in the framework of the 15-Country Study. Workers with substantial doses from these radiation types were therefore identified and excluded from analyses. Doses from "lower-energy" photons (<100 keV) and from "higher-energy" photons (>3 MeV) were estimated to be small.

BackgroundAccording to a fundamental law of radiobiology (“Law of Bergonié and Tribondeau”, 1906), the brain is a paradigm of a highly differentiated organ with low mitotic activity, and is thus radio-resistant. This assumption has been challenged by recent evidence discussed in the present review.ResultsIonizing radiation is an established environmental cause of brain cancer. Although direct evidence is lacking in contemporary fluoroscopy due to obvious sample size limitation, limited follow-up time and lack of focused research, anecdotal reports of clusters have appeared in the literature, raising the suspicion that brain cancer may be a professional disease of interventional cardiologists. In addition, although terminally differentiated neurons have reduced or mild proliferative capacity, and are therefore not regarded as critical radiation targets, adult neurogenesis occurs in the dentate gyrus of the hippocampus and the olfactory bulb, and is important for mood, learning/memory and normal olfactory function, whose impairment is a recognized early biomarker of neurodegenerative diseases. The head doses involved in radiotherapy are high, usually above 2 Sv, whereas the low-dose range of professional exposure typically involves lifetime cumulative whole-body exposure in the low-dose range of < 200 mSv, but with head exposure which may (in absence of protection) arrive at a head equivalent dose of 1 to 3 Sv after a professional lifetime (corresponding to a brain equivalent dose around 500 mSv).ConclusionsAt this point, a systematic assessment of brain (cancer and non-cancer) effects of chronic low-dose radiation exposure in interventional cardiologists and staff is needed.