Association between lymph node silicosis and lung silicosis in 4,384 German uranium miners with lung cancer

This study investigates the association between lymph node-only and lung silicosis in uranium miners with lung cancer and exposure to quartz dust. Tissue slides of 4,384 German uranium miners with lung cancer were retrieved from an autopsy archive and reviewed by 3 pathologists regarding silicosis in the lungs and lymph nodes. Cumulative exposure to quartz dust was assessed with a quantitative job-exposure matrix. The occurrence of silicosis by site was investigated with regression models for exposure to quartz dust. Miners with lung silicosis had highest cumulative quartz exposure, followed by lymph node-only silicosis and no silicosis. At a cumulative quartz exposure of 40 mg/m(3) × years, the probability of lung silicosis was above 90% and the likelihood of lymph node-only silicosis and no silicosis do not differ anymore. The results support that lymph node silicosis can precede lung silicosis, at least in a proportion of subjects developing silicosis, and that lung silicosis strongly depends on the cumulative quartz dose.     

Mortality from lung cancer in Ontario uranium miners.

Mortality from lung cancer was greater in Ontario uranium miners than in the general male population of Ontario (observed = 152, expected = 67.6, standardised mortality ratio 225, 95% confidence interval 191-264). Part of the excess of lung cancer may be because the proportion of men who are smokers or have smoked is greater in uranium miners than in Ontario men. Smoking does not explain the whole excess. Mortality from lung cancer in Ontario uranium miners is clearly related to exposure to short lived radon progeny. The excess relative risk of lung cancer from the same degree of exposure to short lived radon progeny is greatest five to 14 years after exposure and less subsequently. It is greater in men under the age of 55 years and less in older men. Part of the excess of lung cancer mortality in Ontario uranium miners is probably also due to exposure to arsenic that occurred earlier in gold mines. In Ontario uranium miners, the lung cancer mortality from exposure to arsenic increases as the intensity of exposure to short lived radon progeny increases. This finding is consistent with the hypothesis that the risk of lung cancer from exposure to arsenic is enhanced by exposure to other carcinogens. In Ontario uranium miners, the proportion of lung cancers that are small cell carcinomas is greater than in the general population. The proportion of small cell carcinomas is especially great five to 14 years after exposure to short lived radon progeny and in men who die from lung cancer at younger ages.     

Radon Exposure,IL-6 Promoter Variants,and Lung Squamous Cell Carcinoma in Former Uranium Miners

Background:

High radon exposure is a risk factor for squamous cell carcinoma, a major lung cancer histology observed in former uranium miners. Radon exposure can cause oxidative stress, leading to pulmonary inflammation. Interleukin-6 (IL-6) is a pro-carcinogenic inflammatory cytokine that plays a pivotal role in lung cancer development.

Objectives:

We assessed whether single nucleotide polymorphisms (SNPs) in the IL6 promoter are associated with lung cancer in former uranium miners with high occupational exposure to radon gas.

Methods:

Genetic associations were assessed in a case–control study of former uranium miners (242 cases and 336 controls). A replication study was performed using data from the Gene Environment Association Studies (GENEVA) Genome Wide Association Study (GWAS) of Lung Cancer and Smoking. Functional relevance of the SNPs was characterized using in vitro approaches.

Results:

We found that rs1800797 was associated with squamous cell carcinoma in miners and with a shorter time between the midpoint of the period of substantial exposure and diagnosis among the cases. Furthermore, rs1800797 was also associated with lung cancer among never smokers in the GENEVA dataset. Functional studies identified that the risk allele was associated with increased basal IL-6 mRNA level and greater promoter activity. Furthermore, fibroblasts with the risk allele showed greater induction of IL-6 secretion by hydrogen peroxide or benzo[a]pyrene diolepoxide treatments.

Conclusions:

An IL6 promoter variant was associated with lung cancer in uranium miners and never smokers in two external study populations. The associations are strongly supported by the functional relevance that the IL6 promoter SNP affects basal expression and carcinogen-induced IL-6 secretion.

Citation:

Leng S, Thomas CL, Snider AM, Picchi MA, Chen W, Willis DG, Carr TG, Krzeminski J, Desai D, Shantu A, Lin Y, Jacobson MR, Belinsky SA. 2016. Radon exposure, IL-6 promoter variants, and lung squamous cell carcinoma in former uranium miners. Environ Health Perspect 124:445–451; http://dx.doi.org/10.1289/ehp.1409437     

Carcinoma of the lung in Ontario gold miners: possible aetiological factors.

A cohort of 54,128 men who worked in Ontario mines was observed for mortality between 1955 and 1986. Most of these men worked in nickel, gold, or uranium mines; a few worked in silver, iron, lead/zinc, or other ore mines. If mortality that occurred after a man had started to mine uranium was excluded, an excess of carcinoma of the lung was found among the 13,603 Ontario gold miners in the study (standardised mortality ratio (SMR) 129, 95% confidence interval (95% CI) 115-145) and in men who began to mine nickel before 1936 (SMR 141, 95% CI 105-184). The excess mortality from lung cancer in the gold miners was confined to men who began gold mining before 1946. No increase in the mortality from carcinoma of the lung was evident in men who began mining gold after the end of 1945, in men who began mining nickel after 1936, or in men who mined ores other than gold, nickel, and uranium. In the gold mines each year of employment before the end of 1945 was associated with a 6.5% increase in mortality from lung cancer 20 or more years after the miner began working the mines (95% CI 1.6-11.4%); each year of employment before the end of 1945 in mines in which the host rock contained 0.1% arsenic was associated with a 3.1% increase in lung cancer 20 years or more after exposure began (95% CI 1.1-5.1%); and each working level month of exposure to radon decay products was associated with a 1.2% increase in mortality from lung cancer five or more years after exposure began (95% CI 0.02-2.4%). A comparison of two models shows that the excess of lung cancer mortality in Ontario gold miners is associated with exposure to high dust concentrations before 1946, with exposure to arsenic before 1946, and with exposure to radon decay products. No association between the increased incidence of carcinoma of the lung in Ontario gold miners and exposure to mineral fibre could be detected. It is concluded that the excess of carcinoma of the lung in Ontario gold miners is probably due to exposure to arsenic and radon decay products.     

Carcinoma of the lung in Ontario gold miners: possible aetiological factors.

A cohort of 54,128 men who worked in Ontario mines was observed for mortality between 1955 and 1986. Most of these men worked in nickel, gold, or uranium mines; a few worked in silver, iron, lead/zinc, or other ore mines. If mortality that occurred after a man had started to mine uranium was excluded, an excess of carcinoma of the lung was found among the 13,603 Ontario gold miners in the study (standardised mortality ratio (SMR) 129, 95% confidence interval (95% CI) 115-145) and in men who began to mine nickel before 1936 (SMR 141, 95% CI 105-184). The excess mortality from lung cancer in the gold miners was confined to men who began gold mining before 1946. No increase in the mortality from carcinoma of the lung was evident in men who began mining gold after the end of 1945, in men who began mining nickel after 1936, or in men who mined ores other than gold, nickel, and uranium. In the gold mines each year of employment before the end of 1945 was associated with a 6.5% increase in mortality from lung cancer 20 or more years after the miner began working the mines (95% CI 1.6-11.4%); each year of employment before the end of 1945 in mines in which the host rock contained 0.1% arsenic was associated with a 3.1% increase in lung cancer 20 years or more after exposure began (95% CI 1.1-5.1%); and each working level month of exposure to radon decay products was associated with a 1.2% increase in mortality from lung cancer five or more years after exposure began (95% CI 0.02-2.4%). A comparison of two models shows that the excess of lung cancer mortality in Ontario gold miners is associated with exposure to high dust concentrations before 1946, with exposure to arsenic before 1946, and with exposure to radon decay products. No association between the increased incidence of carcinoma of the lung in Ontario gold miners and exposure to mineral fibre could be detected. It is concluded that the excess of carcinoma of the lung in Ontario gold miners is probably due to exposure to arsenic and radon decay products.     

Clinical measures, smoking, radon exposure, and risk of lung cancer in uranium miners.

OBJECTIVES: Exposure to the radioactive daughters of radon is associated with increased risk of lung cancer in mining populations. An investigation of incidence of lung cancer following a clinical survey of Ontario uranium miners was undertaken to explore whether risk associated with radon is modified by factors including smoking, radiographic silicosis, clinical symptoms, the results of lung function testing, and the temporal pattern of radon exposure. METHODS: Miners were examined in 1974 by a respiratory questionnaire, tests of lung function, and chest radiography. A random selection of 733 (75%) of the original 973 participants was followed up by linkage to the Ontario Mortality and Cancer Registries. RESULTS: Incidence of lung cancer was increased threefold. Risk of lung cancer among miners who had stopped smoking was half that of men who continued to smoke. There was no interaction between smoking and radon exposure. Men with lung function test results consistent with airways obstruction had an increased risk of lung cancer, even after adjustment for cigarette smoking. There was no association between radiographic silicosis and risk of lung cancer. Lung cancer was associated with exposures to radon daughters accumulated in a time window four to 14 years before diagnosis, but there was little association with exposures incurred earlier than 14 years before diagnosis. Among the men diagnosed with lung cancer, the mean and median dose rates were 2.6 working level months (WLM) a year and 1.8 WLM/year in the four to 14 year exposure window. CONCLUSIONS: Risk of lung cancer associated with radon is modified by dose and time from exposure. Risk can be substantially decreased by stopping smoking.     

Schneeberg lung disease and uranium mining in the saxon ore mountains (Erzgebirge)

The so-called Schneeberg lung disease is a form of bronchial or alveolar carcinoma caused by the effects of the radioactive gas radon and of its radioactive short half-life daughter products. This type of radiation-induced occupational cancer is the most common and the most important radiation injury among workers occupationally exposed to ionizing radiation. There have been many deaths from lung cancer, especially in the Soviet uranium mines in the Erzgebirge of Saxony in the former German Democratic Republic. The history of disease in these miners extends over five centuries; the first observations of their health hazard start in the Middle Ages. The discovery of the lung cancer component was made toward the end of the nineteenth century, and the suspicion that a connection might exist between this cancer type and exposure to ionizing radiation was voiced at the beginning of the twentieth century. In the first half of this century, further research was carried out on this disease in the Schneeberg area of the Erzgebirge. Before the end of World War II, guidelines were set up to define the acceptable limits of radon exposure in the ore mines of Saxony. After World War II, the American uranium mines in the Colorado Plateau used the German research results as a basis for working out their own radiation protection standard. The uranium mines under Soviet occupation in the former GDR, on the contrary, paid no attention to these research findings. For many years, no precautions were taken for the miners' working conditions. The consequence of this serious omission was an estimated 9,000 fatal cases of lung cancer among these underground miners. High concentrations of radon are to be found in indoor air of homes in some districts of the Erzgebirge, suggesting an increasing lung cancer risk for the local inhabitants. The significance of this finding is evaluated. © 1993 Wiley-Liss, Inc.     

Uranium mining in East Germany ("Wismut"): health consequences, occupational medical care and workers' compensation

Underground uranium mining was performed in East Germany after World War II on a large scale. Working conditions were very poor during the post-war years from approx. 1946 to 1955. During later years mining conditions improved. In 1990, uranium production was generally stopped as a consequence of German reunification. A company-based health care system commenced in the early years with an annual routine medical check-up including chest X-ray. A central Wismut institution for occupational medicine was founded in 1968. Since reunification, the German Workers' Compensation Board is organizing post-exposural occupational medical care and compensation for former miners. Compensable occupational diseases include silicosis and Schneeberg lung disease (bronchial carcinoma of uranium miners). A current topic is the question of acknowledgement of extrapulmonary malignoma as a compensable disease in uranium miners. With a certain cumulated exposure as a prerequisite, bone and liver cancer and certain types of leukemia are likely to be accepted.     

Mortality experience of haematite mine workers in China

The mortality risk of iron ore (haematite) miners between 1970 and 1982 was investigated in a retrospective cohort study of workers from two mines, Longyan and Taochong, in China. The cohort was limited to men and consisted of 5406 underground miners and 1038 unexposed surface workers. Among the 490 underground miners who died, 205 (42%) died of silicosis and silicotuberculosis and 98 (20%) of cancer, including 29 cases (5.9%) of lung cancer. The study found an excess risk of non-malignant respiratory disease and of lung cancer among haematite miners. The standardised mortality ratio for lung cancer compared with nationwide male population rates was significantly raised (SMR = 3.7), especially for those miners who were first employed underground before mechanical ventilation and wet drilling were introduced (SMR = 4.8); with jobs involving heavy exposure to dust, radon, and radon daughters (SMR = 4.2); with a history of silicosis (SMR = 5.3); and with silicotuberculosis (SMR = 6.6). No excess risk of lung cancer was observed in unexposed workers (SMR = 1.2). Among current smokers, the risk of lung cancer increased with the level of exposure to dust. The mortality from all cancer, stomach, liver, and oesophageal cancer was not raised among underground miners. An excess risk of lung cancer among underground mine workers which could not be attributed solely to tobacco use was associated with working conditions underground, especially with exposure to dust and radon gas and with the presence of non-malignant respiratory disease. Because of an overlap of exposures to dust and radon daughters, the independent effects of these factors could not be evaluated.     

Mortality experience of haematite mine workers in China.

The mortality risk of iron ore (haematite) miners between 1970 and 1982 was investigated in a retrospective cohort study of workers from two mines, Longyan and Taochong, in China. The cohort was limited to men and consisted of 5406 underground miners and 1038 unexposed surface workers. Among the 490 underground miners who died, 205 (42%) died of silicosis and silicotuberculosis and 98 (20%) of cancer, including 29 cases (5.9%) of lung cancer. The study found an excess risk of non-malignant respiratory disease and of lung cancer among haematite miners. The standardised mortality ratio for lung cancer compared with nationwide male population rates was significantly raised (SMR = 3.7), especially for those miners who were first employed underground before mechanical ventilation and wet drilling were introduced (SMR = 4.8); with jobs involving heavy exposure to dust, radon, and radon daughters (SMR = 4.2); with a history of silicosis (SMR = 5.3); and with silicotuberculosis (SMR = 6.6). No excess risk of lung cancer was observed in unexposed workers (SMR = 1.2). Among current smokers, the risk of lung cancer increased with the level of exposure to dust. The mortality from all cancer, stomach, liver, and oesophageal cancer was not raised among underground miners. An excess risk of lung cancer among underground mine workers which could not be attributed solely to tobacco use was associated with working conditions underground, especially with exposure to dust and radon gas and with the presence of non-malignant respiratory disease. Because of an overlap of exposures to dust and radon daughters, the independent effects of these factors could not be evaluated.     

Lung cancer in a nonsmoking underground uranium miner

Working in mines is associated with acute and chronic occupational disorders. Most of the uranium mining in the United States took place in the Four Corners region of the Southwest (Arizona, Colorado, New Mexico, and Utah) and on Native American lands. Although the uranium industry collapsed in the late 1980s, the industry employed several thousand individuals who continue to be at increased risk for developing lung cancers. We present the case of a 72-year-old Navajo male who worked for 17 years as an underground uranium miner and who developed lung cancer 22 years after leaving the industry. His total occupational exposure to radon progeny was estimated at 506 working level months. The miner was a life-long nonsmoker and had no other significant occupational or environmental exposures. On the chest X-ray taken at admission into the hospital, a right lower lung zone infiltrate was detected. The patient was treated for community-acquired pneumonia and developed respiratory failure requiring mechanical ventilation. Respiratory failure worsened and the patient died 19 days after presenting. On autopsy, a 2.5 cm squamous cell carcinoma of the right lung arising from the lower lobe bronchus, a right broncho-esophageal fistula, and a right lower lung abscess were found. Malignant respiratory disease in uranium miners may be from several occupational exposures; for example, radon decay products, silica, and possibly diesel exhaust are respiratory carcinogens that were commonly encountered. In response to a growing number of affected uranium miners, the Radiation Exposure Compensation Act (RECA) was passed by the U.S. Congress in 1990 to make partial restitution to individuals harmed by radiation exposure resulting from underground uranium mining and above-ground nuclear tests in Nevada.     

Health effects in underground uranium miners

The health effects associated with uranium miners have received much attention in the last 30 years. Although mortality rates are elevated for such causes as accidents and nonmalignant respiratory disease, lung cancer caused by exposure to radon decay products is the primary hazard to underground uranium miners. This review summarizes studies of eight cohorts of radium miners, and examines several pooled analyses that provide the best understanding of the radon/lung cancer relationship. The relative risk of lung cancer is linearly related to cumulative exposure to radon decay products. The excess relative risk decreases with attained age and time since exposure. An inverse exposure-rate effect exists, such that prolonged exposure at low levels of radon is more hazardous than shorter exposures to higher levels. The linear no-threshold model used in most epidemiologic studies has been attacked by some as overestimating risk at indoor radon levels. These arguments are rejected by this reviewer.     

Relation of arsenic exposure to lung cancer among tin miners in Yunnan Province, China.

The relation of mining and smelting exposure to arsenic and lung cancer was studied among tin miners in Yunnan Province in the People's Republic of China. Interviews were conducted in 1985 with 107 living tin miners who had lung cancer and an equal number of age matched controls from among tin miners without lung cancer to obtain information on risk factors for lung cancer including detailed history of employment and tobacco use. Occupational history was combined with industrial hygiene data to estimate cumulative arsenic exposure. Similar methods were also used to estimate radon exposure for simultaneous evaluation in this analysis. The results indicate that subjects in the highest quarter of cumulative arsenic exposure have a relative risk of 22.6 compared with subjects without exposure after adjusting for tobacco and radon exposure, and a positive dose response relation was observed. Simultaneous evaluation of arsenic and tobacco exposure indicates a greater risk for arsenic, whereas simultaneous assessment of arsenic and radon exposure suggests radon to be the greater risk. There is no evidence of synergism between arsenic and tobacco exposure. Among arsenic exposed individuals, cases of lung cancer have longer duration but lower average intensity of arsenic exposure than controls, indicating that duration of exposure to arsenic may be more important than intensity in the aetiology of lung cancer. Finally, risk of lung cancer among workers exposed to arsenic only in mining is only slightly less than for miners whose exposure to arsenic was limited to smelting, although risks are highest when workers were exposed to both mining and smelting.     

Relation of radon exposure and tobacco use to lung cancer among tin miners in Yunnan Province, China

We studied the relation of radon exposure and tobacco use to lung cancer among tin miners in Yunnan Province in the People's Republic of China. Interviews were conducted in 1985 with 107 living tin miners with lung cancer and an equal number of age-matched controls from among tin miners without lung cancer to obtain information on lung cancer risk factors including a detailed history of employment and tobacco use. Occupational history was combined with extensive industrial hygiene data to estimate cumulative working level months (WLM) of radon daughter exposure. Similar data were also used to estimate arsenic exposure for control in the analysis. Results indicate an increased risk of lung cancer for water pipe smoking, a traditional form of tobacco use practiced in 91% of cases and 85% of controls. Ever use of water pipes was associated with a twofold elevation in risk when compared with tobacco abstainers, and a dose-response relation was observed with increasing categories of pipe-year (dose times duration) usage. Estimated WLM of radon exposure varied from 0 to 1,761 among subjects but averaged 515 in cases versus only 244 in controls. Analyses indicated that the persons in the highest quarter of the radon exposure distribution had an odds ratio (OR) = 9.5 (95% confidence interval = 2.7-33.1) compared to persons without radon exposure after controlling for arsenic exposure and other potential confounders. Examination of duration and rate of radon exposure indicated higher risk associated with long duration as opposed to high rate of exposure. Cross-categorizations of radon exposure and tobacco use suggest greater risk associated with radon exposure than tobacco in these workers.     

Mortality from lung cancer among silicotic patients in Sardinia: an update study with 10 more years of follow up

OBJECTIVES—To evaluate the association between silica, silicosis and lung cancer, the mortality of 724 patients with silicosis, first diagnosed by standard chest x ray film between 1964 and 1970, has been analysed by a cohort study extended to 31 December 1997.METHODS—Smoking and detailed occupational histories were available for each member of the cohort as well as the estimated lifetime exposure to respirable silica dust and radon daughters. Two independent readers blindly classified standard radiographs according to the 12 point International Labour Organisation (ILO) scale. Lung function tests meeting the American Thoracic Society''s criteria were available for 665 patients. Standardised mortality ratios (SMRs) for selected causes of death were based on the age specific Sardinian regional death rates.RESULTS—The mortality for all causes was significantly higher than expected (SMR 1.35, 95% confidence interval (95% CI) 1.24 to 1.46) mainly due to tuberculosis (SMR 22.0) and to non-malignant chronic respiratory diseases (NMCRD) (SMR 6.03). All cancer deaths were within the expected numbers (SMR 0.93; 95% CI 0.76 to 1.14). The SMR for lung cancer was 1.37 (95% CI 0.98 to 1.91, 34 observed), increasing to 1.65 (95% CI 0.98 to 2.77) allowing for 20 years of latency since the first diagnosis of silicosis. Although mortality from NMCRD was strongly associated to the severity of radiological silicosis and to the extent of the cumulative exposure to silica, SMR for lung cancer was weakly related to the ILO categories and to the cumulative exposure to silica dust only after 20 years of lag interval. A significant excess of deaths from lung cancer (SMR 2.35) was found among silicotic patients previously employed in underground metal mines characterised by a relatively high airborne concentration of radon daughters and among ever smokers who showed an airflow obstruction at the time of the first diagnosis of silicosis (SMR 3.29). Mortality for lung cancer related to exposure was evaluated with both the Cox''s proportional hazards modelling within the entire cohort and a nested case-control study (34 cases of lung cancer and 136 matched controls). Both multivariate analyses did not show any significant association with cumulative exposure to silica or severity of silicosis, but confirmed the association between mortality for lung cancer and relatively high exposure to radon, smoking, and airflow obstruction as significant covariates.CONCLUSIONS—The findings indicate that the slightly increased mortality for lung cancer in this cohort of silicotic patients was significantly associated with other risk factors—such as cigarette smoking, airflow obstruction, and estimated exposure to radon daughters in underground mines—rather than to the severity of radiological silicosis or to the cumulative exposure to crystalline silica dust itself.     

Influence of quartz exposure on lung cancer types in cases of lymph node–only silicosis and lung silicosis in German uranium miners

Inhaled crystalline quartz is a carcinogen. Analyses show differences in the distribution of lung cancer types depending on the status of silicosis. Using 2,524 lung tumor cases from the WISMUT autopsy repository database, silicosis was differentiated into cases without silicosis in lung parenchyma and its lymph nodes, with lymph node–only silicosis, or with lung silicosis including lymph node silicosis. The proportions of adenocarcinoma, squamous cell carcinoma, and small-cell lung carcinoma mortality for increasing quartz exposures were estimated in a multinomial logistic regression model. The relative proportions of the lung cancer subtypes in lymph node–only silicosis were more similar to lung silicosis than without any silicosis. The results support the hypothesis that quartz-related carcinogenesis in case of lymph node–only silicosis is more similar to that in lung silicosis than in without silicosis.     

Mortality in uranium miners in west Bohemia: a long-term cohort study.

A cohort of 4320 uranium miners in West Bohemia who started work at the mines during 1948 to 1959 and worked there for at least four years were followed up to the end of 1990 to determine cause specific mortality risks in relation to exposures in the mines. The miners had experienced high radon exposures, on average 219 working level months during their uranium mining careers, for which detailed measurements were available. They had also been exposed to high arsenic levels in one of the two major mines, and to dust. New follow up methods, not previously used for occupational cohorts in Czechoslovakia, were utilised. By the end of follow up 2415 (56%) of the cohort were known to have died. Overall mortality was significantly raised compared with that in the general population (relative risk (RR) = 1.56, 95% confidence interval (95% CI) 1.50-1.63), with significantly raised risks of lung cancer (RR = 5.08, 95% CI 4.71-5.47), accidents (RR = 1.59, 95% CI 1.34-1.87), homicide (RR = 5.57, 95% CI 2.66-10.21), mental disorders (RR = 5.18, 95% CI 2.83-8.70), cirrhosis (RR = 1.51, 95% CI 1.16-1.94), and non-rheumatic circulatory diseases (RR = 1.16, 95% CI 1.08-1.25). The relative risk of lung cancer was greatest four to 14 years after entry to the mines. Relative risks for homicide and accidents were raised up to 25 years from entry but not after this. Substantial significantly raised risks at 15 to 24 years after entry occurred for cirrhosis, non-rheumatic circulatory diseases,a nd pneumonia and other respiratory infections. Sizeable significantly raised risks at 25 and more years after entry, but not earlier, were present for mental disorders, tuberculosis, and non-malignant non-infectious respiratory conditions. No specific causes showed risks significantly related to age at entry to mining. Risk of lung cancer was significantly positively related to radon exposure, estimated arsenic exposure, and duration of work in the mines, but no other cause was significantly positively related to these variables. The raised risk of lung cancer in uranium miners, which is well established, is related aetiologically to radon exposure, and in the present cohort it may also in part have been due to exposure to arsenic. The raised risks of accidents, tuberculosis, and non-infectious respiratory diseases have also been seen in other uranium mining cohorts, and are likely to reflect the dangerous and dusty working conditions and the confined spaces in which work occurred. The cirrhosis and homicide deaths probably related to the lifestyle associated with mining. The raised risk of circulatory diseases does not seem to be related to radon or arsenic exposure; its causes are unclear. The use of multiple follow up methods was found to be mortality in the cohort.     

Radon progeny exposure and lung cancer risk among non-smoking uranium miners

Studies of miners provide the basis for public health efforts to reduce residential radon progeny exposure. Because the preponderance of households do not have members who smoke indoors, studies of non-smoking miners contribute essential data for risk assessments for residential radon progeny exposure. We studied a cohort of 2,209 never-smokers who were underground uranium miners employed in the western U.S. from 1956 to the early 1990's and who participated in a screening program for lung cancer conducted by Saccomanno and colleagues. After determining the vital status and cause of death in the cohort, we conducted a nested case-control study of 55 lung cancer deaths in males and 3 age-matched controls for each case. The relative risk of lung cancer was 29.2 (95% CI 5.1, 167.2) for miners with greater than 1,450 WLM compared with those exposed to less than 80 WLM. Temporal factors affected risk, including average dose rate, which was inversely associated with lung cancer risk, and the length of time since last exposure, which was directly associated with decreased risk. As in studies of non-smokers and smokers combined, the exposure response relationship in never-smokers was consistent with a decreased slope at higher WLM, which resulted, in part, from an inverse dose rate effect.     

Characteristics of the German uranium miners cohort study

To evaluate the risk of cancer associated with low and high levels of radon exposure one of the largest single cohort studies on uranium miners is being conducted in Germany including 58,721 men who were employed for at least 6 mo between 1946 and 1989 at the former Wismut uranium company in Eastern Germany. Information on job history, smoking, dust, and arsenic was collected from the original payrolls and the medical records. Exposure to radon and its progeny was estimated by using a detailed job-exposure matrix. The first mortality follow-up determining the vital status as of 31 December 1998 has been started. The cohort includes 49,342 exposed miners who have worked underground or in processing/milling facilities and 9,379 never-exposed workers. Miners who had been exposed for the first time between 1946 and 1954 (n = 19,865), the years with the poorest working conditions, show higher mean cumulative radon exposures (709 working level months, WLM) and a longer duration of exposure (mean = 13 y) than those with the first exposure between 1955 to 1970 (121 WLM and 11 y, n = 14,155) or after 1970 (10 WLM and 6 y, n = 15,322), respectively. Information on smoking is available for 38% of the cohort, demonstrating that most miners were heavy smokers. In the first mortality follow-up a total of about 15,000 deceased men including about 2,200 lung cancer deaths are expected. The main strengths of the study are its size and the large group of workers having received low exposures over relatively long periods of time.