Factors Modifying the Radon-Related Lung Cancer Risk at Low Exposures and Exposure Rates among German Uranium Miners.

It is still not fully understood whether and how factors such as time, age and smoking modify the relationship between lung cancer and radon at low exposures and exposure rates. Improved knowledge is necessary for the dose conversion of radon in working level month (WLM) into effective dose, as currently discussed by the International Commission on Radiological Protection (ICRP). An update of the German uranium miner cohort study (n = 58,974 men) with a 10-year extension of mortality follow-up (1946-2013) was used to further examine this issue. Internal Poisson regression was applied to estimate the excess relative risk (ERR) for lung cancer mortality per unit of cumulative radon exposure in WLM with exponential time-related effect modifiers. In the full cohort restricted to <100 WLM the estimated overall ERR/WLM was 0.006 [95% confidence interval (CI): 0.003; 0.010] based on 1,254 lung cancer deaths and 1,620,190 person-years at risk. Both age at and time since exposure turned out to be important modifiers of the ERR/WLM and were included in the final model. Here, the ERR/WLM centered on age at exposure of 30 years, and 20 years since exposure was 0.016 (95% CI: 0.008; 0.028). This value decreased statistically significantly by approximately 40% and 60% for each 10-year increase in age at exposure and time since exposure, respectively. The joint effect of smoking and radon exposure was investigated in the sub-cohort of miners hired in 1960 or later, which includes data on smoking status. The centered ERR/WLM was slightly higher for non/light smokers compared to moderate/heavy smokers (0.022 versus 0.013). The current findings provide evidence for an increased lung cancer risk at low radon exposures or exposure rates that is modified by age and time. The observed risk is lower, but statistically compatible to those of other miner studies at low exposures or exposure rates. These findings reject an additive- and support a sub- to (supra-) multiplicative interaction between smoking and radon.

Lung cancer risk at low radon exposure rates in German uranium miners.

BACKGROUND: A determination of the risk of lung cancer at low levels of radon exposure is important for occupational radiation protection. METHODS: The risk of death from lung cancer at low radon exposure rates was investigated in the subcohort of 26,766 German uranium miners hired in 1960 or later. RESULTS: A clear association between lung cancer mortality (n=334 deaths) and cumulative exposure to radon in working level months (WLM) was found. The excess relative risk per WLM was 0.013 (95% confidence intervals: 0.007; 0.021). CONCLUSIONS: The present findings provide strong evidence for an increased lung cancer risk after long-term exposure to low radon exposure rates among Wismut miners. The results are compatible to those from residential radon studies and miner studies restricted to low levels.

Mortality from internal and external radiation exposure in a cohort of male German uranium millers, 1946-2008.

PURPOSE: To examine exposure-response relationships between ionizing radiation and several mortality outcomes in a subgroup of 4,054 men of the German uranium miner cohort study, who worked between 1946 and 1989 in milling facilities, but never underground or in open pit mines. METHODS: Mortality follow-up was from 1946 to 2008, accumulating 158,383 person-years at risk. Cumulative exposure to radon progeny in working level months (WLM) (mean = 8, max = 127), long-lived radionuclides from uranium ore dust in kBqh/m(3) (mean = 3.9, max = 132), external gamma radiation in mSv (mean = 26, max = 667) and silica dust was estimated by a comprehensive job-exposure matrix. Internal Poisson regression models were applied to estimate the linear excess relative risk (ERR) per unit of cumulative exposure. RESULTS: Overall, a total of 457, 717 and 111 deaths occurred from malignant cancer, cardiovascular diseases and non-malignant respiratory diseases, respectively. Uranium ore dust and silica dust were not associated with mortality from any of these disease groups. A statistically significant relationship between cumulative radon exposure and mortality from all cancers (ERR/100 WLM = 1.71; p = 0.02), primarily due to lung cancer (n = 159; ERR/100 WLM = 3.39; p = 0.05), was found. With respect to cumulative external gamma radiation, an excess of mortality of solid cancers (n = 434; ERR/Sv = 1.86; p = 0.06), primarily due to stomach cancer (n = 49, ERR/Sv = 10.0; p = 0.12), was present. CONCLUSION: The present findings show an excess mortality from lung cancer due to radon exposure and from solid cancers due to external gamma radiation in uranium millers that was not statistically significant. Exposure to uranium was not associated with any cause of death, but absorbed organ doses were estimated to be low.

Application of the ELDO approach to assess cumulative eye lens doses for interventional cardiologists.

In preparation of a large European epidemiological study on the relation between eye lens dose and the occurrence of lens opacities, the European ELDO project focused on the development of practical methods to estimate retrospectively cumulative eye lens dose for interventional medical professionals exposed to radiation. The present paper applies one of the ELDO approaches, correlating eye lens dose to whole-body doses, to assess cumulative eye lens dose for 14 different Finnish interventional cardiologists for whom annual whole-body dose records were available for their entire working period. The estimated cumulative left and right eye lens dose ranged from 8 to 264 mSv and 6 to 225 mSv, respectively. In addition, calculations showed annual eye lens doses sometimes exceeding the new ICRP annual limit of 20 mSv. The work also highlights the large uncertainties associated with the application of such an approach proving the need for dedicated dosimetry systems in the routine monitoring of the eye lens dose.

A review of the results from the German Wismut uranium miners cohort.

The Wismut cohort is currently the largest single study on the health risks associated with occupational exposures to ionising radiation and dust accrued during activities related to uranium mining. The cohort has ∼59 000 male workers, first employed between 1946 and 1989, at the Wismut Company in Germany. The main effect is a statistically significant increase in mortality from lung cancer with both increasing cumulative radon exposure and silica dust exposure. Risks for cancers of the extrathoracic airways, all extra-pulmonary cancers and cardiovascular diseases associated with radiation exposures have been evaluated. Cohort mortality rates for some other cancer sites, stomach and liver, are statistically significantly increased in relation to the general population, but not statistically significantly related to occupational exposures. No associations between leukaemia mortality and occupational doses of ionising radiation were found.

Silica dust, radon and death from non-malignant respiratory diseases in German uranium miners.

OBJECTIVE: To quantify the relationship between death from non-malignant respiratory diseases (NMRD) and exposure to silica dust or radon in a cohort of 58,690 former German uranium miners. METHODS: In the follow-up period from 1946 to 2008, a total of 2336 underlying deaths from NMRDs occurred, including 715 deaths from chronic obstructive pulmonary diseases (COPD) and 975 deaths from silicosis or other pneumoconiosis. Exposure to respirable crystalline silica and radon was individually assessed by means of a comprehensive job-exposure matrix. Risk analyses were based on a linear Poisson regression model with the baseline stratified by age, calendar year and duration of employment. RESULTS: There was no increase in risk of death from COPDs or any other NMRDs in relation to cumulative exposure to silica (mean=5.9, max=56 mg/m(3)-years), except in the group of deaths from silicosis or other pneumoconiosis. Here, a strong non-linear increase in risk was observed. Cumulative radon exposure (mean=280; max=3224 Working Level Months) was not related to death from COPDs or any other NMRDs. CONCLUSIONS: The present findings do not indicate a relationship between mortality from COPD with silica dust or radon. However, validity of cause of death and lack of control for smoking remain potential sources of bias.

A correlation study of eye lens dose and personal dose equivalent for interventional cardiologists.

This paper presents the dosimetry part of the European ELDO project, funded by the DoReMi Network of Excellence, in which a method was developed to estimate cumulative eye lens doses for past practices based on personal dose equivalent values, H(p)(10), measured above the lead apron at several positions at the collar, chest and waist levels. Measurement campaigns on anthropomorphic phantoms were carried out in typical interventional settings considering different tube projections and configurations, beam energies and filtration, operator positions and access routes and using both mono-tube and biplane X-ray systems. Measurements showed that eye lens dose correlates best with H(p)(10) measured on the left side of the phantom at the level of the collar, although this correlation implicates high spreads (41 %). Nonetheless, for retrospective dose assessment, H(p)(10) records are often the only option for eye dose estimates and the typically used chest left whole-body dose measurement remains useful.

Radiation dose dependent risk of liver cancer mortality in the German uranium miners cohort 1946-2003.

An increased risk of mortality from primary liver cancers among uranium miners has been observed in various studies. An analysis of the data from a German uranium miner cohort (the 'Wismut cohort') was used to assess the relationship with ionising radiation. To that end the absorbed organ dose due to high and low linear energy transfer radiation was calculated for 58 987 miners with complete information on radiation exposure from a detailed job-exposure matrix. 159 deaths from liver cancer were observed in the follow-up period from 1946 to 2003. Relative risk models with either linear or categorical dependence on high and low linear energy transfer radiation liver doses were fitted by Poisson regression, stratified on age and calendar year. The linear trend of excess relative risk in a model with both low and high linear transfer radiation is -0.8 (95% confidence interval (CI): -3.7, 2.1) Gy(-1) and 48.3 (95% CI: -32.0, 128.6) Gy(-1) for low and high linear energy transfer radiation, respectively, and thus not statistically significant for either dose. The increase of excess relative risk with equivalent liver dose is 0.57 (95% CI: -0.69, 1.82) Sv(-1). Adjustment for arsenic only had a negligible effect on the radiation risk. In conclusion, there is only weak evidence for an increase of liver cancer mortality with increasing radiation dose in the German uranium miners cohort considered. However, both a lack of statistical power and potential misclassification of primary liver cancer are issues.

External gamma radiation and mortality from cardiovascular diseases in the German WISMUT uranium miners cohort study, 1946-2008.

It is currently unclear whether exposure of the heart and vascular system, at lifetime accumulated dose levels relevant to the general public (<500 mGy), is associated with an increased risk of cardiovascular disease. Therefore, data from the German WISMUT cohort of uranium miners were investigated for evidence of a relationship between external gamma radiation and death from cardiovascular diseases. The cohort comprises 58,982 former employees of the Wismut company. There were 9,039 recorded deaths from cardiovascular diseases during the follow-up period from 1946 to 2008. Exposures to external gamma radiation were estimated using a detailed job-exposure matrix. The exposures were based on expert ratings for the period 1946-1954 and measurements thereafter. The excess relative risk (ERR) per unit of cumulative gamma dose was obtained with internal Poisson regression using a linear ERR model with baseline stratification by age and calendar year. The mean cumulative gamma dose was 47 mSv for exposed miners (86 %), with a maximum of 909 mSv. No evidence for an increase in risk with increasing cumulative dose was found for mortality from all cardiovascular diseases (ERR/Sv = -0.13; 95 % confidence interval (CI): -0.38; 0.12) and ischemic heart diseases (n = 4,613; ERR/Sv = -0.03; 95 % CI: -0.38, 0.32). However, a statistically insignificant increase (n = 2,073; ERR/Sv = 0.44; 95 % CI: -0.16, 1.04) for mortality from cerebrovascular diseases was observed. Data on smoking, diabetes, and overweight are available for subgroups of the cohort, indicating no major correlation with cumulative gamma radiation. Confounding by these factors or other risk factors, however, cannot be excluded. In conclusion, the results provide weak evidence for an increased risk of death due to gamma radiation only for cerebrovascular diseases.

Quantitative relationship between silica exposure and lung cancer mortality in German uranium miners, 1946-2003.

BACKGROUND: In 1996 and 2009, the International Agency for Research on Cancer classified silica as carcinogenic to humans. The exposure-response relationship between silica and lung cancer risk, however, is still debated. Data from the German uranium miner cohort study were used to further investigate this relationship. METHODS: The cohort includes 58677 workers with individual information on occupational exposure to crystalline silica in mg m(-3)-years and the potential confounders radon and arsenic based on a detailed job-exposure matrix. In the follow-up period 1946-2003, 2995 miners died from lung cancer. Internal Poisson regression with stratification by age and calendar year was used to estimate the excess relative risk (ERR) per dust-year. Several models including linear, linear quadratic and spline functions were applied. Detailed adjustment for cumulative radon and arsenic exposure was performed. RESULTS: A piecewise linear spline function with a knot at 10 mg m(-3)-years provided the best model fit. After full adjustment for radon and arsenic no increase in risk <10 mg m(-3)-years was observed. Fixing the parameter estimate of the ERR in this range at 0 provided the best model fit with an ERR of 0.061 (95% confidence interval: 0.039, 0.083) >10 mg m(-3)-years. CONCLUSION: The study confirms a positive exposure-response relationship between silica and lung cancer, particularly for high exposures.

Radon and risk of death from cancer and cardiovascular diseases in the German uranium miners cohort study: follow-up 1946-2003.

Data from the German uranium miners cohort study were analyzed to investigate the radon-related risk of mortality from cancer and cardiovascular diseases. The Wismut cohort includes 58,987 men who were employed for at least 6 months from 1946 to 1989 at the former Wismut uranium mining company in Eastern Germany. By the end of 2003, a total of 3,016 lung cancer deaths, 3,355 deaths from extrapulmonary cancers, 5,141 deaths from heart diseases and 1,742 deaths from cerebrovascular diseases were observed. Although a number of studies have already been published on various endpoints in the Wismut cohort, the aim of the present analyses is to provide a direct comparison of the magnitude of radon-related risk for different cancer sites and cardiovascular diseases using the same data set, the same follow-up period and the same statistical methods. A specific focus on a group of cancers of the extrathoracic airways is also made here, due to the assumed high organ doses from absorbed radon progeny. Internal Poisson regression was used to estimate the excess relative risk (ERR) per unit of cumulative exposure to radon in working level months (WLM) and its 95% confidence limits (CI). There was a statistically significant increase in the risk of lung cancer with increasing radon exposure (ERR/WLM = 0.19%; 95% CI: 0.17%; 0.22%). A smaller, but also statistically significant excess was found for cancers of the extrathoracic airways and trachea (ERR/WLM = 0.062%; 95% CI: 0.002%; 0.121%). Most of the remaining nonrespiratory cancer sites showed a positive relationship with increasing radon exposure, which, however, did not reach statistical significance. No increase in risk was noted for coronary heart diseases (ERR/WLM = 0.0003%) and cerebrovascular diseases (ERR/WLM = 0.001%). The present data provide clear evidence of an increased radon-related risk of death from lung cancer, some evidence for an increased radon-related risk of death from cancers of the extrathoracic airways and some other extrapulmonary cancers, and no evidence for mortality from cardiovascular diseases. These findings are consistent with the results of other miner studies and dosimetric calculations for radon-related organ doses.

Radon and risk of extrapulmonary cancers: results of the German uranium miners' cohort study, 1960-2003.

Data from the German miners' cohort study were analysed to investigate whether radon in ambient air causes cancers other than lung cancer. The cohort includes 58,987 men who were employed for at least 6 months from 1946 to 1989 at the former Wismut uranium mining company in Eastern Germany. A total of 20,684 deaths were observed in the follow-up period from 1960 to 2003. The death rates for 24 individual cancer sites were compared with the age and calendar year-specific national death rates. Internal Poisson regression was used to estimate the excess relative risk (ERR) per unit of cumulative exposure to radon in working level months (WLM). The number of deaths observed (O) for extrapulmonary cancers combined was close to that expected (E) from national rates (n=3340, O/E=1.02; 95% confidence interval (CI): 0.98-1.05). Statistically significant increases in mortality were recorded for cancers of the stomach (O/E=1.15; 95% CI: 1.06-1.25) and liver (O/E=1.26; 95% CI: 1.07-1.48), whereas significant decreases were found for cancers of the tongue, mouth, salivary gland and pharynx combined (O/E=0.80; 95% CI: 0.65-0.97) and those of the bladder (O/E=0.82; 95% CI: 0.70-0.95). A statistically significant relationship with cumulative radon exposure was observed for all extrapulmonary cancers (ERR/WLM=0.014%; 95% CI: 0.006-0.023%). Most sites showed positive exposure-response relationships, but these were insignificant or became insignificant after adjustment for potential confounders such as arsenic or dust exposure. The present data provide some evidence of increased risk of extrapulmonary cancers associated with radon, but chance and confounding cannot be ruled out.

Lung cancer risk among German male uranium miners: a cohort study, 1946-1998.

From 1946 to 1990 extensive uranium mining was conducted in the southern parts of the former German Democratic Republic. The overall workforce included several 100,000 individuals. A cohort of 59,001 former male employees of the Wismut Company was established, forming a large retrospective uranium miners' cohort for the time period 1946-1998. Mean duration of follow-up was 30.5 years with a total of 1 801,630 person-years. Loss to follow-up was low at 5.3%. Of the workers, 16,598 (28.1%) died during the study period. Based on 2388 lung cancer deaths, the radon-related lung cancer risk is evaluated. The excess relative risk (ERR) per working level month (WLM) was estimated as 0.21% (95% CI: 0.18-0.24). It was dependent on time since exposure and on attained age. The highest ERR/WLM was observed 15-24 years after exposure and in the youngest age group (<55 years of age). While a strong inverse exposure-rate effect was detected for high exposures, no significant association was detected at exposures below 100 WLM. Excess relative risk /WLM was not modified by duration of exposure. The results would indicate the need to re-estimate the effects of risk modifying factors in current risk models as duration of exposure did not modify the ERR/WLM and there was only a modest decline of ERR/WLM with increasing time since exposure.

Mortality from cardiovascular diseases in the German uranium miners cohort study, 1946-1998.

An increased risk of cardiovascular diseases after exposure to low doses of ionizing radiation has been suggested among the atomic bomb survivors. Few and inconclusive results on this issue are available from miner studies. A positive correlation between coronary heart disease mortality and radon exposure has been reported in the Newfoundland fluorspar miners study, yet low statistical power due to small sample size was of concern. To get further insight into this controversial issue, data from the German uranium miners cohort study were used, which is by far the largest miner study up to date. The cohort includes 59,001 male subjects who were employed for at least six months between 1946 and 1989 at the former Wismut uranium company in Eastern Germany. Exposure to radon, long-lived radionuclides and external gamma radiation was estimated by using a detailed job-exposure matrix. About 16,598 cohort members were deceased until 31 December 1998, including 5,417 deaths from cardiovascular diseases. Linear Poisson regression models were used to estimate the excess relative risk (ERR) per unit of cumulative radiation exposure after adjusting for attained age and calendar period. No trend in risk of circulatory diseases with increasing cumulative exposure to either radon [ERR per 100 working level month: 0.0006; 95% confidence limit (CI): -0.004 to 0.006], external gamma radiation (ERR per Sv: -0.26, 95% CI: -0.6 to 0.05) or long-lived radionuclides (ERR per 100 kBqh/m3: -0.2, 95% CI: -0.5 to 0.06), respectively, was observed. This was also true for the sub-group heart disease and stroke. Our findings do not support an association between cardiovascular disease mortality and exposure to radiation among miners, yet low doses and uncontrolled confounding hamper interpretation.

The German uranium miners cohort study: feasibility and first results.

In Germany, the largest single cohort study on uranium miners to date is being conducted. The cohort includes about 64,000 workers of the former Wismut company in eastern Germany. Inclusion criteria were: a date of employment between 1946 and 1989, a minimum period of employment of 180 days, and complete information on working history. Due to poor working conditions in the late 1940s and early 1950s, miners were exposed to high levels of radiation, while later radiation exposure was significantly reduced. The aim of the cohort study is to evaluate the risk of lung cancer and other cancers associated with several indicators of exposure to radon and its progeny, with particular attention to low levels of radiation. Radon exposure will be estimated by a detailed job- exposure matrix. Some information about smoking, dust and arsenic is already available. About 49,000 miners are defined as exposed (underground or processing), while the internal control group (surface only) consists of 15,000 workers. A total of 1,436 lung cancer deaths among cohort members have been reported. The first mortality follow-up will be finished early in 2002, and a total of about 3,000 lung cancer deaths are expected by then.

Discrimination and association processes for faces and non-faces: the effect of rotation.

Most current theories of face perception claim that inversion leaves the coding of non-face stimuli largely unaffected, while causing a qualitative change in the coding of faces. Empirical support for this hypothesis mainly stems from recognition studies which typically show a larger inversion decrement for faces than for other stimuli. Several recent studies using experimental paradigms that do not contain a substantial memory component have however yielded contradicting results. This observation suggests that the disproportionate effect of inversion for faces might be related to the presence, or absence, of a memory component in the experimental task. In order to explore this hypothesis we investigated the effect of inversion within a discrimination learning paradigm, which contains a memory component comparable to that included in a recognition paradigm. We compared the effect of rotation on discrimination and association processes for faces and cars, Subjects learned to discriminate pairs of similar faces and similar cars and to associated them with neutral responses. The stimulus pairs were presented upright, inverted, and additionally in two intermediate orientations. We found that discrimination performance was generally better for faces than for cars and that associations were learned faster for faces than for cars. However, we did not find any evidence that rotation affected discrimination and association processes for faces differently than for cars. In this sense, our results provide no evidence for the hypothesis that memory processes are responsible for disproportionate effect of inversion which is found in recognition experiments.