Extended analysis of solid cancer incidence among nuclear industry workers in the UK 1955-2011: comparison of workers first hired in earlier and later periods.

To address points arising from the recent study of nuclear workers in the USA and the International Nuclear Workers Study (INWORKS), concerning the difference in solid cancer risk estimates between those first hired in earlier and later calendar years, subsidiary analyses were conducted on a cohort of 172 452 workers in the National Registry for Radiation Workers (NRRW) from the UK. A total of 18 310 incident first primary solid cancer cases were registered in the period from 1955 until 2011 in the NRRW cohort and workers accrued 5.25 million person-years of follow-up. Incidences rates of all solid cancers combined, lung cancer and solid cancer excluding lung cancer were examined in terms of external radiation doses in the full cohort and in a sub-cohort of workers who had no record of internal exposure monitoring and were defined by the periods of first hire before and after the beginning of the years 1960, 1965 and 1970. All analyses were carried out using Poisson Regression. These analyses demonstrated that only for lung cancer between the pre-1965 and post-1964 periods is there strong evidence for a difference in the risks using the NRRW full cohort. In the other calendar period breakdowns and for the other cancer groups, there is no clear evidence of differences in the risks. The NRRW estimation of risks between recent and early workers is not generally consistent with the US workers cohort or the INWORKS evaluations that later hired workers are at much higher solid cancer risk than earlier hired workers, although INWORKS contains a significant part of the latest updated NRRW cohort as well as the US data. The conclusion that the INWORKS and US study data demonstrate a real difference in excess solid cancer risk from external radiation exposure between earlier and later workers is premature. The results presented here should also be treated with caution because of the limited corroborating evidence from other published studies. Information on internal doses, neutron doses as well as non-radiation factors such as smoking and asbestos exposure would be needed to make definitive inferences.

Shape of radiation dose response relationship for ischaemic heart disease mortality and its interpretation: analysis of the national registry for radiation workers (NRRW) cohort.

Statistically significant increases in ischemic heart disease (IHD) mortality with cumulative occupational external radiation dose were observed in the National Registry for Radiation Workers (NRRW) cohort. There were 174 541 subjects in the NRRW cohort. The start of follow up was 1955, and the end of the follow-up for each worker was chosen as the earliest date of death or emigration, their 85th birthday or 31 December 2011. The dose-response relationship showed a downward curvature at a higher dose level >0.4 Sv with the overall shape of the dose-response relationship best described by a linear-quadratic model. The smaller risk at dose >0.4 Sv appears to be primarily associated with workers who started employment at a younger age (<30 years old) and those who were employed for more than 30 years. We modelled the dose response by age-at-first exposure. For the age-at-first exposure of 30+ years old, a linear dose-response was the best fit. For age-at-first exposure <30 years old, there was no evidence of excess risk of IHD mortality for radiation doses below 0.1 Sv or above 0.4 Sv, excess risk was only observed for doses between 0.1-0.4 Sv. For this age-at-first exposure group, it was also found that the doses they received when they were less than 35 years old or greater than 50 years old did not contribute to any increased IHD risk.

Effective doses and risks from medical diagnostic x-ray examinations for male and female patients from childhood to old age.

The consideration of risks from medical diagnostic x-ray examinations and their justification commonly relies on estimates of effective dose, although the quantity is actually a health-detriment-weighted summation of organ/tissue-absorbed doses rather than a measure of risk. In its 2007 Recommendations, the International Commission on Radiological Protection (ICRP) defines effective dose in relation to a nominal value of stochastic detriment following low-level exposure of 5.7 × 10-2Sv-1, as an average over both sexes, all ages, and two fixed composite populations (Asian and Euro-American). Effective dose represents the overall (whole-body) dose received by a person from a particular exposure, which can be used for the purposes of radiological protection as set out by ICRP, but it does not provide a measure that is specific to the characteristics of the exposed individual. However, the cancer incidence risk models used by ICRP can be used to provide estimates of risk separately for males and females, as a function of age-at-exposure, and for the two composite populations. Here, these organ/tissue-specific risk models are applied to estimates of organ/tissue-specific absorbed doses from a range of diagnostic procedures to derive lifetime excess cancer incidence risk estimates; the degree of heterogeneity in the distribution of absorbed doses between organs/tissues will depend on the procedure. Depending on the organs/tissues exposed, risks are generally higher in females and notably higher for younger ages-at-exposure. Comparing lifetime cancer incidence risks per Sv effective dose from the different procedures shows that overall risks are higher by about a factor of two to three for the youngest age-at-exposure group, 0-9 yr, than for 30-39 yr adults, and lower by a similar factor for an age-at-exposure of 60-69 yr. Taking into account these differences in risk per Sv, and noting the substantial uncertainties associated with risk estimates, effective dose as currently formulated provides a reasonable basis for assessing the potential risks from medical diagnostic examinations.

Radiation risks of lymphoma and multiple myeloma incidence in the updated NRRW-3 cohort in the UK: 1955-2011.

The effect of external radiation on lymphoma, including non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL) and multiple myeloma (MM) incidence was evaluated in the National Registry for Radiation Workers based upon the third analysis cohort but with an additional 10 years of follow-up. The study includes 172 452 workers, of whom (90%) were men with 5.25 million person-years of follow-up from 1955 through to the end of 2011. A total of 711 cases of NHL, 113 cases of HL and 279 cases of MM were registered. Poisson regression was used to estimate the excess relative risk per unit of cumulative exposure to ionising radiation. A statistically significant association was found between radiation dose and the incidence of NHL and MM. There was no evidence of radiation associated excess risk for HL. The reported associations are based on a very small proportion of exposed workers, in particular among workers with cumulative doses above 0.5 Sv so should be treated with caution, further investigations are necessary to confirm our results.

Mortality and cancer incidence 1952-2017 in United Kingdom participants in the United Kingdom's atmospheric nuclear weapon tests and experimental programmes.

This study examines the mortality and cancer incidence experience among men who took part in the United Kingdom's atmospheric nuclear weapon tests between 1952-67. A cohort of 21 357 servicemen and male civilians from the UK who participated in the tests and a group of 22 312 controls were followed between 1952 and 2017. Analyses of mortality and cancer incidence were conducted. The overall mortality rate in the test participants was slightly higher relative risk (RR = 1.02, 90% CI 1.00-1.05,p= 0.04) than that in the control group. This difference was driven by similar increased risks for both all cancers combined (RR 1.03, 90% CI 1.00-1.07) and all non-cancer diseases (RR = 1.02, 90% CI 1.00-1.05). Leukaemia excluding chronic lymphatic incidence showed evidence of being raised relative to controls (RR = 1.38, 90% CI 1.10-1.75,p= 0.01). Leukaemia risks were driven by increased risks for chronic myeloid leukaemia (CML) (RR = 2.43, 90% CI 1.43-4.13,p= 0.003). Among non-cancer outcomes only cerebrovascular diseases showed increases in participants relative to controls. UK nuclear weapon tests participants have lower mortality rates compared to the national population although rates are slightly (2%) higher than in the study control group. Variation in background characteristics, that could not be accounted for in the analysis (e.g. smoking habits, diet), are a possible explanation for this difference. For leukaemia evidence of increased risk in the early years after the test has generally continued to diminish with time although for CML risks have persisted. There was some evidence that participants had higher mortality rates from cerebrovascular diseases than those in the control group. Assuming recorded radiation exposures (generally very low) are a true reflection of actual exposures then it is unlikely that any observed health effect will have been caused by radiation exposure.

Risk of cancer associated with low-dose radiation exposure: comparison of results between the INWORKS nuclear workers study and the A-bomb survivors study.

The Life Span Study (LSS) of Japanese atomic bomb survivors has served as the primary basis for estimates of radiation-related disease risks that inform radiation protection standards. The long-term follow-up of radiation-monitored nuclear workers provides estimates of radiation-cancer associations that complement findings from the LSS. Here, a comparison of radiation-cancer mortality risk estimates derived from the LSS and INWORKS, a large international nuclear worker study, is presented. Restrictions were made, so that the two study populations were similar with respect to ages and periods of exposure, leading to selection of 45,625 A-bomb survivors and 259,350 nuclear workers. For solid cancer, excess relative rates (ERR) per gray (Gy) were 0.28 (90% CI 0.18; 0.38) in the LSS, and 0.29 (90% CI 0.07; 0.53) in INWORKS. A joint analysis of the data allowed for a formal assessment of heterogeneity of the ERR per Gy across the two studies (P = 0.909), with minimal evidence of curvature or of a modifying effect of attained age, age at exposure, or sex in either study. There was evidence in both cohorts of modification of the excess absolute risk (EAR) of solid cancer by attained age, with a trend of increasing EAR per Gy with attained age. For leukemia, under a simple linear model, the ERR per Gy was 2.75 (90% CI 1.73; 4.21) in the LSS and 3.15 (90% CI 1.12; 5.72) in INWORKS, with evidence of curvature in the association across the range of dose observed in the LSS but not in INWORKS; the EAR per Gy was 3.54 (90% CI 2.30; 5.05) in the LSS and 2.03 (90% CI 0.36; 4.07) in INWORKS. These findings from different study populations may help understanding of radiation risks, with INWORKS contributing information derived from cohorts of workers with protracted low dose-rate exposures.

Mortality from heart diseases following occupational radiation exposure: analysis of the National Registry for Radiation Workers (NRRW) in the United Kingdom.

Statistically significant increases in heart disease (HD) mortality with cumulative recorded occupational radiation dose from external sources were observed among 174 541 subjects, who were predominately exposed to protracted low doses over a number of years, and were followed up until the end of 2011 in the UK National Registry for Radiation Workers (NRRW) cohort. Amongst the subtypes of HD, the increasing trends with cumulative dose arose for ischaemic heart disease (IHD) and other HD (which includes pulmonary HD, valve disorders, cardiomyopathy, cardiac dysrhythmias, carditis, conduction disorder and ill-defined HD). For IHD, the increased mortality appears to be at least 20 years after first exposure and the excess risk peaked between 30 and 40 years after the first exposure. There was no evidence of excess risk of IHD mortality for cumulative radiation doses below 0.1 Sv. A categorical analysis also showed that the risk falls below the expected value based on a linear trend, for cumulative doses greater than 0.4 Sv; this smaller risk appears to be primarily associated with workers who started employment at a younger age and who were employed for longer than 30 years, reflecting possible healthy worker survivor effect. This analysis provided further evidence that low doses of radiation exposure may be associated with increased risk of IHD. For other HD, the data suggest an increased risk starting around 40 years after the first exposure. The risk was statistically significant raised only for cumulative doses above 0.4 Sv. However, the number of deaths in this group was small and the results need to be interpreted with caution.

Cancer mortality and incidence following external occupational radiation exposure: an update of the 3rd analysis of the UK national registry for radiation workers.

BACKGROUND: This study provides direct evidence of cancer risk from low dose and dose rate occupational external radiation exposures. METHODS: Cancer mortality and incidence were studied in relation to external radiation exposure in the National Registry for Radiation Workers. A cohort of 167,003 workers followed for an average of 32 years was analysed using Poisson regression methods. RESULTS: Mortality and incidence risks were significantly raised for the group of all malignant neoplasms excluding leukaemia (ERR/Sv mortality = 0.28; 90%CI: 0.06, 0.53, ERR/Sv incidence = 0.28; 90%CI: 0.10, 0.48) but with narrower confidence bounds compared with the previous analysis of this cohort reflecting the increased statistical power from the additional 10 years of follow-up information. The linear trends in relative risk for both mortality and incidence of these cancers remained statistically significantly raised when information relating to cumulative doses above 100 mSv was excluded (ERR/Sv mortality = 1.42; 90%CI: 0.51, 2.38 and ERR/Sv incidence = 1.18; 90%CI: 0.47, 1.92). CONCLUSIONS: This study improved the precision of the cancer risk estimates seen in the third analysis of the NRRW cohort. The overall results remain consistent with the risk estimates from the Life Span Study and those adopted in the current ICRP recommendations.

Site-specific Solid Cancer Mortality After Exposure to Ionizing Radiation: A Cohort Study of Workers (INWORKS).

BACKGROUND: There is considerable scientific interest in associations between protracted low-dose exposure to ionizing radiation and the occurrence of specific types of cancer. METHODS: Associations between ionizing radiation and site-specific solid cancer mortality were examined among 308,297 nuclear workers employed in France, the United Kingdom, and the United States. Workers were monitored for external radiation exposure and follow-up encompassed 8.2 million person-years. Radiation-mortality associations were estimated using a maximum-likelihood method and using a Markov chain Monte Carlo method, the latter used to fit a hierarchical regression model to stabilize estimates of association. RESULTS: The analysis included 17,957 deaths attributable to solid cancer, the most common being lung, prostate, and colon cancer. Using a maximum-likelihood method to quantify associations between radiation dose- and site-specific cancer, we obtained positive point estimates for oral, esophagus, stomach, colon, rectum, pancreas, peritoneum, larynx, lung, pleura, bone and connective tissue, skin, ovary, testis, and thyroid cancer; in addition, we obtained negative point estimates for cancer of the liver and gallbladder, prostate, bladder, kidney, and brain. Most of these estimated coefficients exhibited substantial imprecision. Employing a hierarchical model for stabilization had little impact on the estimated associations for the most commonly observed outcomes, but for less frequent cancer types, the stabilized estimates tended to take less extreme values and have greater precision than estimates obtained without such stabilization. CONCLUSIONS: The results provide further evidence regarding associations between low-dose radiation exposure and cancer.

Examining temporal effects on cancer risk in the international nuclear workers' study.

The paper continues the series of publications from the International Nuclear Workers Study cohort that comprises 308,297 workers from France, the United Kingdom and the United States, providing 8.2 million person-years of observation from a combined follow-up period (at earliest 1944 to at latest 2005). These workers' external radiation exposures were primarily to photons, resulting in an estimated average career absorbed dose to the colon of 17.4 milligray. The association between cumulative ionizing radiation dose and cancer mortality was evaluated in general relative risk models that describe modification of the excess relative risk (ERR) per gray (Gy) by time since exposure and age at exposure. Methods analogous to a nested-case control study using conditional logistic regression of sampled risks sets were used. Outcomes included: all solid cancers, lung cancer, leukemias excluding chronic lymphocytic, acute myeloid leukemia, chronic myeloid leukemia, multiple myeloma, Hodgkin lymphoma and non-Hodgkin lymphoma. Significant risk heterogeneity was evident in chronic myeloid leukemia with time since exposure, where we observed increased ERR per Gy estimates shortly after exposure (2-10 year) and again later (20-30 years). We observed delayed effects for acute myeloid leukemia although estimates were not statistically significant. Solid cancer excess risk was restricted to exposure at age 35+ years and also diminished for exposure 30 years prior to attained age. Persistent or late effects suggest additional follow-up may inform on lifetime risks. However, cautious interpretation of results is needed due to analytical limitations and a lack of confirmatory results from other studies.

Collateral contamination concomitant to the polonium-210 poisoning of Mr Alexander Litvinenko.

Mr Litvinenko died on 23 November 2006, having been poisoned with polonium-210 on 1 November, with evidence of a previous poisoning attempt during October 2006. Measurements of 210Po in urine samples were made for a large number of people to determine whether they may have been contaminated. In the majority of cases, measured levels were attributable to the presence of 210Po from normal dietary sources. For a small number of cases, elevated levels provided evidence of direct contamination associated with the poisonings. For one individual, while estimated doses were below thresholds for irreversible organ damage, a notably increased risk of cancer can be inferred. The use of the chelating agent, unithiol, to increase 210Po excretion in this case was only moderately effective in reducing doses received.

Concerted Uranium Research in Europe (CURE): toward a collaborative project integrating dosimetry, epidemiology and radiobiology to study the effects of occupational uranium exposure.

The potential health impacts of chronic exposures to uranium, as they occur in occupational settings, are not well characterized. Most epidemiological studies have been limited by small sample sizes, and a lack of harmonization of methods used to quantify radiation doses resulting from uranium exposure. Experimental studies have shown that uranium has biological effects, but their implications for human health are not clear. New studies that would combine the strengths of large, well-designed epidemiological datasets with those of state-of-the-art biological methods would help improve the characterization of the biological and health effects of occupational uranium exposure. The aim of the European Commission concerted action CURE (Concerted Uranium Research in Europe) was to develop protocols for such a future collaborative research project, in which dosimetry, epidemiology and biology would be integrated to better characterize the effects of occupational uranium exposure. These protocols were developed from existing European cohorts of workers exposed to uranium together with expertise in epidemiology, biology and dosimetry of CURE partner institutions. The preparatory work of CURE should allow a large scale collaborative project to be launched, in order to better characterize the effects of uranium exposure and more generally of alpha particles and low doses of ionizing radiation.

Calculation of lifetime lung cancer risks associated with radon exposure, based on various models and exposure scenarios.

The risk of lung cancer mortality up to 75 years of age due to radon exposure has been estimated for both male and female continuing, ex- and never-smokers, based on various radon risk models and exposure scenarios. We used risk models derived from (i) the BEIR VI analysis of cohorts of radon-exposed miners, (ii) cohort and nested case-control analyses of a European cohort of uranium miners and (iii) the joint analysis of European residential radon case-control studies. Estimates of the lifetime lung cancer risk due to radon varied between these models by just over a factor of 2 and risk estimates based on models from analyses of European uranium miners exposed at comparatively low rates and of people exposed to radon in homes were broadly compatible. For a given smoking category, there was not much difference in lifetime lung cancer risk between males and females. The estimated lifetime risk of radon-induced lung cancer for exposure to a concentration of 200 Bq m(-3) was in the range 2.98-6.55% for male continuing smokers and 0.19-0.42% for male never-smokers, depending on the model used and assuming a multiplicative relationship for the joint effect of radon and smoking. Stopping smoking at age 50 years decreases the lifetime risk due to radon by around a half relative to continuing smoking, but the risk for ex-smokers remains about a factor of 5-7 higher than that for never-smokers. Under a sub-multiplicative model for the joint effect of radon and smoking, the lifetime risk of radon-induced lung cancer was still estimated to be substantially higher for continuing smokers than for never smokers. Radon mitigation-used to reduce radon concentrations at homes-can also have a substantial impact on lung cancer risk, even for persons in their 50 s; for each of continuing smokers, ex-smokers and never-smokers, radon mitigation at age 50 would lower the lifetime risk of radon-induced lung cancer by about one-third. To maximise risk reductions, smokers in high-radon homes should both stop smoking and remediate their homes.

Risks of circulatory diseases among Mayak PA workers with radiation doses estimated using the improved Mayak Worker Dosimetry System 2008.

The new Mayak Worker Dosimetry System 2008 (MWDS-2008) was published in 2013 and supersedes the Doses-2005 dosimetry system for Mayak Production Association (PA) workers. It provides revised external and internal dose estimates based on the updated occupational history data. Using MWDS-2008, a cohort of 18,856 workers first employed at one of the main Mayak PA plants during 1948-1972 and followed up to 2005 was identified. Incidence and mortality risks from ischemic heart disease (IHD) (International Classification of Diseases (ICD)-9 codes 410-414) and from cerebrovascular diseases (CVD) (ICD-9 codes 430-438) were examined in this cohort and compared with previously published risk estimates in the same cohort based on the Doses-2005 dosimetry system. Significant associations were observed between doses from external gamma-rays and IHD and CVD incidence and also between internal doses from alpha-radiation and IHD mortality and CVD incidence. The estimates of excess relative risk (ERR)/Gy were consistent with those estimates from the previous studies based on Doses-2005 system apart from the relationship between CVD incidence and internal liver dose where the ERR/Gy based on MWDS-2008 was just over three times higher than the corresponding estimate based on Doses-2005 system. Adjustment for smoking status did not show any effect on the estimates of risk from internal alpha-particle exposure.

The cancer mortality and incidence experience of workers at British Nuclear Fuels plc, 1946-2005.

The aim of this study was to estimate cancer mortality and incidence risk associated with external radiation exposure in the BNFL cohort of nuclear workers and to determine if these risks are modified by potential for internal exposure. The cohort comprised 64,956 individuals who were employed at the four study sites between 1946 and 2002, followed up to 2005. External radiation exposures as measured by personal dosimeters (generally 'film badges') were available for 42,431 individuals classified as 'radiation workers'. Poisson regression models were used to investigate cancer mortality and incidence in relation to cumulative external radiation exposure using relative risk models. The cohort showed the expected 'healthy worker' effect. This analysis found an increased risk of all cancers associated with external occupational radiation exposure (ERR/Gy = 0.34 90% CI: 0.07; 0.64), with significant excess risks observed for all solid cancers (ERR/Gy = 0.29 90% CI: 0.02; 0.59) and leukaemia excluding CLL (ERR/Gy = 2.60 90% CI: 0.28; 7.01). The overall cancer risk estimates are consistent with values used by national and international bodies in setting radiation protection standards. The slopes of the dose response relationships for all cancer mortality and incidence were found to be significantly less steep for workers exposed to both external radiation and potentially to internal radiation (ERR/Gy = 0.09 90% CI: -0.17; 0.39) when compared to those workers only exposed to external radiation (ERR/Gy = 1.14 90% CI: 0.49; 1.89). Analyses of individual cancer types indicate that this overall result is mainly driven by that for digestive cancers and in particular cancers of the oesophagus. Categorical analyses also revealed that the difference in the dose response relationship between the two groups is only apparent for those exposed to cumulative external doses in excess of 200 mGy. Such differences have also been observed for non-cancer mortality outcomes in this cohort. Further work is required to explain these differences; for example, whether they may result from confounding by internal organ dose or lifestyle factors associated with socio-economic status.

Effects of radiation on respiratory disease mortality: analysis of the national registry for radiation workers in United Kingdom.

PURPOSE: While some evidence of an effect of radiation exposure on respiratory disease at low dose levels has now emerged, there is heterogeneity in the risks between different studies and countries. In this paper, we aim to show the effect of radiation on three different sub-types of respiratory disease mortality through the analysis of the NRRW cohort in UK. MATERIALS AND METHODS: The NRRW cohort consisted of 174,541 radiation workers. Doses to the surface of the body were monitored using individual film badges. Most of the doses are associated with X-rays and gamma rays and to a less extent of beta and neutron particles. The overall mean 10-year lagged lifetime external dose was 23.2 mSv. Some workers were potentially exposed to alpha particles. However, doses from internal emitters were not available for the NRRW cohort. 25% of male workers and 17% of female workers were identified as being monitored for internal exposure. The Poisson regression methods for grouped survival data with a stratified baseline hazard function were used to describe the dependence of the risk on cumulative external radiation dose. The disease was analyzed by the following subgroups: Pneumonia (1066 cases including 17 cases of influenza), COPD and allied disease (1517 cases) and other remaining respiratory diseases (479 cases). RESULTS: There was very little radiation effect on pneumonia mortality, but evidence of a reduction in mortality risk for COPD and allied disease (ERR/Sv= -0.56, 95%CI: -0.94, -0.06; p = .02) and an increase in risk for other respiratory disease mortality (ERR/Sv = 2.30, 95%CI: 0.67, 4.62; p = .01) with increasing cumulative external dose were observed. The effects of radiation were more prominent amongst workers monitored for internal exposure. The reduction in mortality risk of COPD and allied disease per cumulative external dose was statistically significant for the radiation workers monitored for internal exposure (ERR/Sv= -0.59, 95%CI: -0.99, -0.05; p = .017) but not significant among the workers who were not monitored (ERR/Sv= -0.43, 95%CI: -1.20, 0.74; p = .42). A statistically significant increased risk was observed for other respiratory diseases among monitored radiation workers (ERR/Sv = 2.46, 95%CI: 0.69, 5.08; p = .019), but not among unmonitored workers (ERR/Sv = 1.70, 95%CI: -0.82, 5.65; p = .25). CONCLUSION: The effects of radiation exposure can be different depending on the type of respiratory disease. No effect was seen in pneumonia; a reduction in mortality risk of COPD, and increased mortality risk of other respiratory diseases were observed with cumulative external radiation dose. More studies are needed to verify these findings.

Cancer mortality after low dose exposure to ionising radiation in workers in France, the United Kingdom, and the United States (INWORKS): cohort study.

OBJECTIVE: To evaluate the effect of protracted low dose, low dose rate exposure to ionising radiation on the risk of cancer. DESIGN: Multinational cohort study. SETTING: Cohorts of workers in the nuclear industry in France, the UK, and the US included in a major update to the International Nuclear Workers Study (INWORKS). PARTICIPANTS: 309 932 workers with individual monitoring data for external exposure to ionising radiation and a total follow-up of 10.7 million person years. MAIN OUTCOME MEASURES: Estimates of excess relative rate per gray (Gy) of radiation dose for mortality from cancer. RESULTS: The study included 103 553 deaths, of which 28 089 were due to solid cancers. The estimated rate of mortality due to solid cancer increased with cumulative dose by 52% (90% confidence interval 27% to 77%) per Gy, lagged by 10 years. Restricting the analysis to the low cumulative dose range (0-100 mGy) approximately doubled the estimate of association (and increased the width of its confidence interval), as did restricting the analysis to workers hired in the more recent years of operations when estimates of occupational external penetrating radiation dose were recorded more accurately. Exclusion of deaths from lung cancer and pleural cancer had a modest effect on the estimated magnitude of association, providing indirect evidence that the association was not substantially confounded by smoking or occupational exposure to asbestos. CONCLUSIONS: This major update to INWORKS provides a direct estimate of the association between protracted low dose exposure to ionising radiation and solid cancer mortality based on some of the world's most informative cohorts of radiation workers. The summary estimate of excess relative rate solid cancer mortality per Gy is larger than estimates currently informing radiation protection, and some evidence suggests a steeper slope for the dose-response association in the low dose range than over the full dose range. These results can help to strengthen radiation protection, especially for low dose exposures that are of primary interest in contemporary medical, occupational, and environmental settings.

Cerebrovascular Disease Mortality after occupational Radiation Exposure among the UK National Registry for Radiation Workers Cohort.

Exposure to ionizing radiation can damage the cerebrovascular system, however there is uncertainty regarding the effects after chronic exposure to low doses of radiation, such as that experienced by the public and those occupationally exposed. This study uses data from the UK National Registry for Radiation Workers cohort to assess the association between low-dose exposure to external radiation and cerebrovascular disease (CeVD) mortality. Poisson regression was used to estimate the Excess Relative Risk of CeVD mortality per Sievert (ERR/Sv) of radiation exposure. Estimates were obtained for all CeVD combined, ischemic stroke, hemorrhagic stroke and other/ill-defined CeVD. Results were adjusted for attained age, calendar period, sex, employer, industrial category and employment length. 166,812 nuclear workers (3,665,413 person-years) were included. By the end of 2011, 23% were dead including 3,219 deaths with an underlying cause of CeVD. The ERR/Sv for all CeVD deaths was 0.57 (95% CI: 0.00, 1.31; p = 0.05). Increased CeVD mortality rates were observed after doses as low as 10-20 mSv. However, a linear-exponential model fit the data significantly better than a linear model (p = 0.02). In the sub-type analyses, no evidence of linear associations were observed, however the patterns of response appeared to differ and there was some suggestion of an increased risk of hemorrhagic stroke at lower doses. These results are broadly consistent with other occupational cohort studies and suggest external radiation exposure may increase CeVD risk at lower doses than current ICRP protection guidelines suggest. Exploration of factors driving the observed dose-response shape, the potential impact of the healthy worker survivor effect, and further studies of cohorts with data on other potential confounders would be valuable.