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.

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.

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.