Mortality in Underground Miners in a Former Uranium Ore Mine­Results of a Cohort Study Among Former Employees of Wismut AG in Saxony and Thuringia.

BACKGROUND: From 1946 to 1990, more than 400 000 people were employed by Wismut AG, a Soviet/Soviet-German corporation (German abbreviation: SAG/ SDAG), in the East German states of Saxony and Thuringia. In the early years in particular, employees were exposed to large amounts of radon and respirable crystalline silica. METHODS: In a cohort of 35 204 former underground employees of Wismut AG, mortality was analyzed in comparison to the general male population of East Germany, and the pertaining standardized mortality ratios (SMRs) were calculated. RESULTS: 18 510 persons in the study cohort died in the follow-up period 1960-2013. Mortality from lung cancer was 2.36 higher in the study cohort than in the general population (95% confidence interval, [2.28; 2.45]); the associated SMRs rose markedly with increasing radon exposure. Mortality from silicosis and other types of pneumoconiosis was elevated by a factor of 22.62 [21.20; 24.11], and the associated SMRs rose exponentially with increasing exposure to respirable crystalline silica. Mortality from both of these causes was still markedly elevated more than 20 years after Wismut AG had ceased its activities. Mortality from a wide range of other diseases was elevated as well, with the following SMRs: stomach cancer, 1.28 [1.17; 1.40]; liver cancer, 1.34 [1.15; 1.55]; all tumors other than lung cancer, 1.06 [1.02; 1.09]; infections, 1.18 [1.01; 1.38]; cerebrovascular diseases, 1.33 [1.26; 1.41]; and influenza/pneumonia, 1.13 [1.01; 1.27]. Mortality from a small number of other causes was found to be markedly lowered in the study cohort (mental illness, renal diseases, and nervous system diseases). The role of occupational risk factors, lifestyle differences and other reasons for the latter results is unclear. CONCLUSION: Underground miners employed by Wismut AG displayed marked excess mortality due to silicosis/other pneumoconiosis and lung cancer. The contribution of individual occupational risk factors for these and other causes of death with increased SMR are being further investigated in analyses within the study cohort.

Analysis of mortality in a pooled cohort of Canadian and German uranium processing workers with no mining experience.

PURPOSE: Long-term health risks of occupational exposures to uranium processing were examined to better understand potential differences with uranium underground miners and nuclear reactor workers. METHODS: A cohort study of mortality of workers from Port Hope, Canada (1950-1999) and Wismut, Germany (1946-2008) employed in uranium milling, refining, and processing was conducted. Poisson regression was used to evaluate the association between cumulative exposures to radon decay products (RDP) and gamma-rays and causes of death potentially related to uranium processing. RESULTS: The pooled cohort included 7431 workers (270,201 person-years of follow-up). Mean RDP exposures were lower than in miners while gamma-ray doses were higher than in reactor workers. Both exposures were highly correlated (weighted rho = 0.81). Radiation risks of lung cancer and cardiovascular diseases (CVD) in males were increased but not statistically significant and compatible with risks estimated for miners and reactor workers, respectively. Higher RDP-associated CVD risks were observed for exposures 5-14 years prior to diagnosis compared to later exposures and among those employed <5 years. Radiation risks of solid cancers excluding lung cancer were increased, but not statistically significant, both for males and females, while all other causes of death were not associated with exposures. CONCLUSIONS: In the largest study of uranium processing workers to systematically examine radiation risks of multiple outcomes from RDP exposures and gamma-rays, estimated radiation risks were compatible with risks reported for uranium miners and nuclear reactor workers. Continued follow-up and pooling with other cohorts of uranium processing workers are necessary for future comparisons with other workers of the nuclear fuel cycle.

Leukaemia mortality and low-dose ionising radiation in the WISMUT uranium miner cohort (1946-2013).

OBJECTIVES: To examine the risk of death from leukaemia in relation to occupational chronic low-level external and internal radiation exposure in a cohort of 58 972 former German uranium miners with mortality follow-up from 1946 to 2013. METHODS: The red bone marrow (RBM) dose from low-linear energy transfer (LET) (mainly external γ-radiation) and high-LET (mainly radon gas) radiation was estimated based on a job-exposure matrix and biokinetic/dosimetric models. Linear excess relative risks (ERR) and 95% CIs were estimated via Poisson regression for chronic lymphatic leukaemia (CLL) and non-CLL. RESULTS: The mean cumulative low-LET and high-LET RBM doses among the 86% radiation-exposed workers were 48 and 9 mGy, respectively. There was a positive non-significant dose-response for mortality from non-CLL (n=120) in relation to low-LET (ERR/Gy=2.18; 95% CI -0.41 to 6.37) and high-LET radiation (ERR/Gy=16.65; 95% -1.13 to 46.75). A statistically significant excess was found for the subgroup chronic myeloid leukaemia (n=31) in relation to low-LET radiation (ERR/Gy=7.20; 95% CI 0.48 to 24.54) and the subgroup myeloid leukaemia (n=99) (ERR/Gy=26.02; 95% CI 2.55 to 68.99) for high-LET radiation. The ERR/Gy tended to be about five to ten times higher for high-LET versus low-LET radiation; however, the CIs largely overlapped. Results indicate no association of death from CLL (n=70) with either type of radiation. CONCLUSIONS: Our findings indicate an increased risk of death for specific subtypes from non-CLL in relation to chronic low-LET and high-LET radiation, but no such relation for CLL.

Mortality from cancers of the extra-thoracic airways in relation to radon progeny in the Wismut cohort, 1946-2008.

PURPOSE: Inhalation of radon progeny can cause high lung and respiratory tract radiation doses. The aim of this paper was to examine the relationship between radon progeny and cancers of the extra-thoracic airways in the German uranium miner cohort for an extended follow-up through 2008. METHODS: The cohort included 58,690 workers employed between 1946 and 1989 at the Wismut company. Exposure to radon progeny in Working Level Months (WLM) was determined from a comprehensive job-exposure matrix. The mean (max) cumulative exposure to radon among exposed cohort members (86%) was 280 WLM (3,224 WLM). Internal Poisson regression models were applied to estimate the linear Excess Relative Risk (ERR) per unit of cumulative exposure to radon. RESULTS: A small increase in the mortality from all cancers of the extra-thoracic airways combined with increasing cumulative exposure to radon was found (ERR/100 WLM = 0.036, p = 0.12), based on 234 deaths. The estimated ERR per 100 WLM for relevant cancer sub-groups were: 0.017 (p > 0.5) larynx (n = 94); 0.077 (p = 0.20) pharynx (n = 74); and 0.030 (p > 0.5) tongue and mouth (n = 55). CONCLUSION: RESULTS indicated a small but not statistically significant increase in mortality from cancers of the extra-thoracic airways in relation to radon. Low statistical power and uncontrolled confounding were limitations of this study.

Joint analysis of three European nested case-control studies of lung cancer among radon exposed miners: exposure restricted to below 300 WLM.

Analyses of lung cancer risk were carried out using restrictions to nested case-control data on uranium miners in the Czech Republic, France, and Germany. With the data restricted to cumulative exposures below 300 working-level-months (WLM) and adjustment for smoking status, the excess relative risk (ERR) per WLM was 0.0174 (95% CI: 0.009-0.035), compared to the estimate of 0.008 (95% CI: 0.004-0.014) using the unrestricted data. Analysis of both the restricted and unrestricted data showed that time since exposure windows had a major effect; the ERR/WLM was six times higher for more recent exposures (5-24 y) than for more distant exposures (25 y or more). Based on a linear model fitted to data on exposures <300 WLM, the ERR WLM of lung cancer at 30 y after exposure was estimated to be 0.021 (95% CI: 0.011-0.040), and the risks decreased by 47% per decade increase in time since exposure. The results from analyzing the joint effects of radon and smoking were consistent with a sub-multiplicative interaction; the ERR WLM was greater for non-smokers compared with current or ex-smokers, although there was no statistically significant variation in the ERR WLM by smoking status. The patterns of risk with radon exposure from the combined European nested case-control miner analysis were generally consistent with those based on the BEIR VI Exposure-Age-Concentration model. Based on conversions from WLM to time weighted averaged radon concentration (expressed per 100 Bq m), the results from this analysis of miner data were in agreement with those from the joint analysis of the European residential radon studies.

Prostate cancer mortality risk in relation to working underground in the Wismut cohort study of German uranium miners, 1970-2003.

OBJECTIVE: A recent study and comprehensive literature review has indicated that mining could be protective against prostate cancer. This indication has been explored further here by analysing prostate cancer mortality in the German 'Wismut' uranium miner cohort, which has detailed information on the number of days worked underground. DESIGN: An historical cohort study of 58 987 male mine workers with retrospective follow-up before 1999 and prospective follow-up since 1999. SETTING AND PARTICIPANTS: Uranium mine workers employed during the period 1970-1990 in the regions of Saxony and Thuringia, Germany, contributing 1.42 million person-years of follow-up ending in 2003. OUTCOME MEASURE: Simple standardised mortality ratio (SMR) analyses were applied to assess differences between the national and cohort prostate cancer mortality rates and complemented by refined analyses done entirely within the cohort. The internal comparisons applied Poisson regression excess relative prostate cancer mortality risk model with background stratification by age and calendar year and a whole range of possible explanatory covariables that included days worked underground and years worked at high physical activity with γ radiation treated as a confounder. RESULTS: The analysis is based on miner data for 263 prostate cancer deaths. The overall SMR was 0.85 (95% CI 0.75 to 0.95). A linear excess relative risk model with the number of years worked at high physical activity and the number of days worked underground as explanatory covariables provided a statistically significant fit when compared with the background model (p=0.039). Results (with 95% CIs) for the excess relative risk per day worked underground indicated a statistically significant (p=0.0096) small protective effect of -5.59 (-9.81 to -1.36) ×10(-5). CONCLUSION: Evidence is provided from the German Wismut cohort in support of a protective effect from working underground on prostate cancer mortality risk.

Radon, smoking and lung cancer risk: results of a joint analysis of three European case-control studies among uranium miners.

A combined analysis of three case-control studies nested in three European uranium miner cohorts was performed to study the joint effects of radon exposure and smoking on lung cancer death risk. Occupational history and exposure data were available from the cohorts. Smoking information was reconstructed using self-administered questionnaires and occupational medical archives. Linear excess relative risk models adjusted for smoking were used to estimate the lung cancer risk associated with radon exposure. The study includes 1046 lung cancer cases and 2492 controls with detailed radon exposure data and smoking status. The ERR/WLM adjusted for smoking is equal to 0.008 (95% CI: 0.004-0.014). Time since exposure is shown to be a major modifier of the relationship between radon exposure and lung cancer risk. Fitting geometric mixture models yielded arguments in favor of a sub-multiplicative interaction between radon and smoking. This combined study is the largest case-control study to investigate the joint effects of radon and smoking on lung cancer risk among miners. The results confirm that the lung carcinogenic effect of radon persists even when smoking is adjusted for, with arguments in favor of a sub-multiplicative interaction between radon and smoking.

Differences in baseline lung cancer mortality between the German uranium miners cohort and the population of the former German Democratic Republic (1960-2003).

A previous analysis of the radon-related lung cancer mortality risk, in the German uranium miners cohort, using Poisson modeling techniques, noted internal (spontaneous) rates that were higher on average than the external rates by 16.5% (95% CI: 9%; 24%). The main purpose of the present paper is to investigate the nature of, and possible reasons for, this difference by comparing patterns in spontaneous lung cancer mortality rates in a cohort of male miners involved in uranium extraction at the former Wismut mining company in East Germany with national male rates from the former German Democratic Republic. The analysis is based on miner data for 3,001 lung cancer deaths, 1.76 million person-years for the period 1960-2003, and national rates covering the same calendar-year range. Simple "age-period-cohort" graphical analyses were applied to assess the main qualitative differences between the national and cohort baseline lung cancer rates. Some differences were found to occur mainly at higher attained ages above 70 years. Although many occupational risk factors may have contributed to these observed age differences, only the effects of smoking have been assessed here by applying the Peto-Lopez indirect method for calculating smoking attributability. It is inferred that the observed age differences could be due to the greater prevalence of smoking and more mature smoking epidemic in the Wismut cohort compared to the general population of the former German Democratic Republic. In view of these observed differences between external population-based rates and internal (spontaneous) cohort baseline lung cancer rates, it is strongly recommended to apply only the internal rates in future analyses of uranium miner cohorts.

Radon and the risk of cancer mortality--internal Poisson models for the German uranium miners cohort.

Uranium mining occurred between 1946 and 1990 at the former Wismut mining company in East Germany. 58,987 male former employees form the largest single uranium miners cohort, which has been followed up for causes of mortality occurring from the beginning of 1946 to the end of 2003. The purpose of this paper is to present the radon exposure related cancer mortality risk based on 20,920 deaths, 2 million person-years, and 6,373 cancers. The latter include 3,016 lung cancers and 3,053 extrapulmonary solid cancers. Internal Poisson regression was used to estimate the excess relative risk (ERR) per unit of cumulative radon exposure in Working Level Months (WLM) for all major sites and for the follow-up period from 1946 to 2003. The simple cohort ERR WLM for lung cancer is 0.20% [95% confidence interval (CI): 0.17%; 0.22%]. The ERR model for lung cancer is linear in radon exposure with exponential effect modifiers that depend on age at median exposure, time since median exposure, and radon exposure-rate. In this model the central estimate of ERR WLM is 1.06% (95% CI: 0.69%; 1.42%) for an age at median exposure of 33 y, a time since median exposure of 11 y, and an exposure-rate of 2.7 WL. This central ERR decreases by 5% for each unit exposure-rate increase. The ERR decreases by 32% with each decade increase in age at median exposure and also decreases by 54% with each decade increase in time since median exposure. The ERR WLM for all extrapulmonary solid cancers combined without effect modification is 0.014% (95% CI: 0.006%; 0.023%). The ERR model for extrapulmonary solid cancer is linear in radon exposure with an exponential effect modifier which depends on age-attained. In this model the central estimate of ERR WLM is 0.040% (95% CI: -0.001%; 0.082%) for an age-attained of 44. The ERR decreases by 37% with each decade increase in age-attained. The highest ERR WLM, after lung, is observed for cancers of the pharynx (0.16%), tongue/mouth (0.045%), and liver (0.04%).

The influence of radon exposures on lung cancer mortality in German uranium miners, 1946-2003.

Extensive uranium extraction took place from 1946 until 1990 at the former Wismut mining company in East Germany. A total of 58,987 male former employees of this company form the largest single uranium miners cohort that has been followed up for causes of mortality occurring from the beginning of 1946 to the end of 2003. The purpose of this study was to investigate and evaluate different forms of models for the radon exposure-related lung cancer mortality risk based on 3,016 lung cancer deaths and 2 million person years. Other exposure covariables such as occupational exposure to external gamma radiation, long-lived radionuclides, arsenic, fine dust and silica dust are available. The standardized mortality ratio for lung cancer is 2.03 (95% CI: 1.96; 2.10). The simple cohort excess relative risk (ERR/WLM) for lung cancer is estimated as 0.0019 (95% CI: 0.0016; 0.0022). The BEIR VI model produced risks similar to those obtained with a selected mathematically continuous ERR model for lung cancer. The continuous model is linear in radon exposure with exponential effect modifiers that depend on the whole range of age at median exposure, time since median exposure, and radon exposure rate. In this model the central estimate of ERR/WLM is 0.0054 (95% CI: 0.0040; 0.0068) for an age at median exposure of 30 years, a time since median exposure of 20 years, and a mean exposure rate of 3 WL. The ERR decreases by 5% for each unit of exposure-rate increase. The ERR decreases by 28% with each decade increase in age at median exposure and also decreases by 51% with each decade increase in time since median exposure. The method of determination of radon exposure (i.e., whether the exposures were estimated or measured) did not play an important role in the determination of the ERR. The other exposure covariables were found to have only minor confounding influences on the ERR/WLM for the finally selected continuous model when included in an additive way.

Accounting for smoking in the radon-related lung cancer risk among German uranium miners: results of a nested case-control study.

The possible confounding effect of smoking on radon-associated risk for lung cancer mortality was investigated in a case-control study nested in the cohort of German uranium miners. The study included 704 miners who died of lung cancer and 1,398 controls matched individually for birth year and attained age. Smoking status was reconstructed from questionnaires and records from the mining company's health archives for 421 cases and 620 controls. Data on radon exposure were taken from a job-exposure matrix. Smoking adjusted odds ratios for lung cancer in relation to cumulative radon exposure have been calculated with conditional logistic regression. The increase in risk per Working Level Month (WLM) was assessed with a linear excess relative risk (ERR) model taking smoking into account as a multiplicative factor. In addition, the potential impact of temporal factors on the ERR per WLM was examined. Lung cancer mortality risk increased with increasing radon exposure, yielding a crude ERR per WLM of 0.25% (95% CI: 0.13-0.46%). Adjustment for smoking led only to marginal changes of the radon-associated lung cancer risks. The adjusted ERR per WLM was very similar (0.23%, 95%-CI: 0.11-0.46%) to the crude risk and to the risk found in the Wismut cohort study. This stability of the radon-related lung cancer risks with and without adjustment for smoking suggests that smoking does not act as a major confounder in this study and presumably also not in the cohort study.