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.

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.

Extended analysis of solid cancer incidence among the Nuclear Industry Workers in the UK: 1955-2011.

Radiation worker studies provide direct estimates of cancer risk after protracted low-dose exposures to external X-ray and gamma-ray irradiations. The National Registry for Radiation Workers (NRRW) started in 1976 and has become the largest epidemiological program of research on nuclear workers in the UK. Here, we report on the relationship between solid cancer incidence and external radiation at the low-dose levels in 172,452 NRRW cohort members of whom (90%) were men. This study is based on 5.25 million person-years of follow-up from 1955 through the end of 2011. In the range of accumulated low doses two-thirds of workers have doses of less than 10 mSv. This study is an updated analysis of solid cancer incidence data with an additional 10 years of follow-up over the previous analysis of the NRRW cohort (NRRW-3). A total of 18,310 cases of solid cancers based on a 10-year lag were registered and of these 43% of the solid cancer cases occurred during the latest 10 years. Poisson regression was used to investigate the relationship between solid cancers risk and protracted chronic low-dose radiation exposure. This study demonstrated for solid cancers a rapid decrease of risk at high external doses that appeared to be driven by the workers who were monitored for potential exposure to internal emitters and who had also received relatively high external doses. Among cohort members only exposed to external radiation, a strong association was found between external dose and solid cancers (ERR/Sv = 0.52, 95% CI: 0.11; 0.96, based on 13,199 cases). A similar pattern is also seen for lung cancer. Excluding lung cancer from the grouping of all solid cancers resulted in evidence of a linear association with external radiation dose (ERR/Sv = 0.24, 95% CI: 0.01; 0.49, based on 15,035 cases), so suggesting some degree of confounding by smoking. Statistically significantly increasing trends with dose were seen for cancers of the colorectal, bladder and pleura cancer. Some of these results should be treated with caution because of the limited corroborating evidence from other published studies. Information on internal doses as well as non-radiation factors such smoking would be helpful to make more definitive inferences.

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.

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.

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.

Ischaemic heart disease incidence and mortality in an extended cohort of Mayak workers first employed in 1948-1982.

OBJECTIVE: Incidence and mortality from ischaemic heart disease (IHD) was studied in an extended cohort of 22,377 workers first employed at the Mayak Production Association during 1948-82 and followed up to the end of 2008. METHODS: Relative risks and excess relative risks per unit dose (ERR/Gy) were calculated based on the maximum likelihood using Epicure software (Hirosoft International Corporation, Seattle, WA). Dose estimates used in analyses were provided by an updated "Mayak Worker Dosimetry System-2008". RESULTS: A significant increasing linear trend in IHD incidence with total dose from external γ-rays was observed after having adjusted for non-radiation factors and dose from internal radiation {ERR/Gy = 0.10 [95% confidence interval (CI): 0.04 to 0.17]}. The pure quadratic model provided a better fit of the data than did the linear one. No significant association of IHD mortality with total dose from external γ-rays after having adjusted for non-radiation factors and dose from internal alpha radiation was observed in the study cohort [ERR/Gy = 0.06 (95% CI: <0 to 0.15)]. A significant increasing linear trend was observed in IHD mortality with total absorbed dose from internal alpha radiation to the liver after having adjusted for non-radiation factors and dose from external γ-rays in both the whole cohort [ERR/Gy = 0.21 (95% CI: 0.01 to 0.58)] and the subcohort of workers exposed at alpha dose <1.00 Gy [ERR/Gy = 1.08 (95% CI: 0.34 to 2.15)]. No association of IHD incidence with total dose from internal alpha radiation to the liver was found in the whole cohort after having adjusted for non-radiation factors and external gamma dose [ERR/Gy = 0.02 (95% CI: not available to 0.10)]. Statistically significant dose effect was revealed in the subcohort of workers exposed to internal alpha radiation at dose to the liver <1.00 Gy [ERR/Gy = 0.44 (95% CI: 0.09 to 0.85)]. CONCLUSION: This study provides strong evidence of IHD incidence and mortality association with external γ-ray exposure and some evidence of IHD incidence and mortality association with internal alpha-radiation exposure. ADVANCES IN KNOWLEDGE: It is the first time the validity of internal radiation dose estimates has been shown to affect the risk of IHD incidence.

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.

Ischemic heart disease in nuclear workers first employed at the Mayak PA in 1948-1972.

Following an earlier study of incidence and mortality of ischemic heart disease (IHD) published in 2010, a second analysis has been conducted based on an extended cohort and five additional years of follow-up. The cohort includes 18,763 workers, of whom 25% were females, first employed at the Mayak PA in 1948-1972 and followed up to the end of 2005. Some of these workers were exposed to external gamma rays only, and others were exposed to a mixture of external gamma-rays and internal alpha-particle radiation. A total of 6,134 cases and 2,629 deaths from IHD were identified in the study cohort. A statistically significant increasing trend was found with total external gamma-ray dose in IHD incidence (ERR/Gy 0.099; 95% CI: 0.045-0.153) after adjusting for non-radiation factors. This value reduced slightly when adjusting for internal liver dose. There was no statistically significant increase trend for internal liver dose in IHD incidence. These findings were consistent with an earlier study. New findings in IHD incidence revealed a statistically significant decrease in IHD incidence among workers exposed to external gamma-rays doses of 0.2-0.5 Gy in relation to the external doses below 0.2 Gy. This decreased risk is heavily influenced by female workers. This finding has never been reported in other studies, and the results should be treated with caution. The findings for IHD mortality are similar to those results in the earlier analysis; there was no statistically significant trend with external gamma-ray dose or for internal liver dose after adjustment for external dose. The risk estimates obtained from these analyses of IHD incidence and mortality in relation to external gamma-rays in the cohort of Mayak workers are generally compatible with those from other large occupational radiation worker studies and the Japanese atomic bomb survivors.

Fitting the two-stage model of carcinogenesis to nested case-control data on the Colorado Plateau uranium miners: dependence on data assumptions.

This paper investigates some problems with the Colorado Plateau uranium miners cohort when fitting the mechanistic model of carcinogenesis of Moolgavkar et al. (MVK model) to nested case-control data for lung cancers. The influence of data for hard rock mining and work histories on the model fitting is examined and found to be highly influential. The question of selecting the most appropriate number of controls per case is also considered. Analyses were carried out assuming that the hard rock mining exposure occurred prior to all other work histories and that miners received no exposure between work histories. The use of less than 15 controls per case was found to seriously restrict the quality of fit of the models. The best fitting, most reliable model contained linear effects of radon exposure on the first mutation rate, the rate of differentiation, and the rate of death of the intermediate cells. An effect of smoking on the growth of the intermediate cells was also included in the model. It is concluded that owing to the complexity of the MVK model and the limited amount of information in this dataset, the reliability of the Colorado Plateau dataset for fitting this type of model, particularly in a case-control format, is questionable.