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.

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.

Occupational dust and radiation exposure and mortality from stomach cancer among German uranium miners, 1946-2003.

OBJECTIVES: 'Dusty occupations' and exposure to low-dose radiation have been suggested as potential risk factors for stomach cancer. Data from the German uranium miner cohort study are used to further evaluate this topic. METHODS: The cohort includes 58 677 miners with complete information on occupational exposure to dust, arsenic and radiation dose based on a detailed job-exposure matrix. A total of 592 stomach cancer deaths occurred in the follow-up period from 1946 to 2003. A Poisson regression model stratified by age and calendar year was used to calculate the excess relative risk (ERR) per unit of cumulative exposure to fine dust or from cumulative absorbed dose to stomach from α or low-LET (low linear energy transfer) radiation. For arsenic exposure, a binary quadratic model was applied. RESULTS: After adjustment for each of the three other variables, a statistically non-significant linear relationship was observed for absorbed dose from low-LET radiation (ERR/Gy=0.30, 95% CI -1.26 to 1.87), α radiation (ERR/Gy=22.5, 95% CI -26.5 to 71.5) and fine dust (ERR/dust-year=0.0012, 95% CI -0.0020 to 0.0043). The relationship between stomach cancer and arsenic exposure was non-linear with a 2.1-fold higher RR (95% CI 0.9 to 3.3) in the exposure category above 500 compared with 0 dust-years. CONCLUSION: Positive statistically non-significant relationships between stomach cancer and arsenic dust, fine dust and absorbed dose from α and low-LET radiation were found. Overall, low statistical power due to low doses from radiation and dust are of concern.

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.