Working Level Months Research Articles

Oxidative Damage in Various Tissues of Rats Exposed to Radon

Oxidative damage can be induced by many environmental stressors. 8-Hydroxydeoxyguanosine (8-OHdG) has been used as a biomarker of oxidative DNA damage in both in vitro and in vivo studies. In the present study, Wistar rats were exposed to radon gas at a concentration of 100,000Bq/m3 for 12 h/d for 30, 60, and 120 d, equivalent to cumulative doses of 60, 120, and 240 working level months (WLM), respectively. Changes in levels of 8-OHdG, reactive oxygen species (ROS), and total antioxidant (T-AOC), as well as expressions of some DNA repair enzymes such as 8-oxoguanine DNA glycosylase (OGG1) and MutT homolog 1 (oxidized purine nucleoside triphosphatase, MTH1), were determined in rat urine, peripheral blood lymphocytes, and lung after exposure to radon. The results revealed an increase in 8-OHdG and ROS levels, a decrease in T-AOC levels, and reduced OGG1 and MTH1 expression levels. The elevated amount of 8-OHdG in urine or lymphocytes was positively correlated with the cumulative exposure dose, whereas OGG1 and MHT1 expression levels in lung were inversely correlated with cumulative exposure dose. These findings indicate that oxidative damage induced by radon may be involved in radon-induced carcinogenesis.

Exposure assessment for a cohort of workers at a former uranium processing facility

Exposure was assessed for a cohort of 6409 workers at a former uranium processing facility as part of a mortality study. Workers at the facility had potential for exposure to a wide variety of radiological and chemical agents including uranium, thorium, radon, external ionizing radiation, acid mists, asbestos, and various solvents. Organ dose from internal exposure to uranium was assessed, along with dose from external ionizing radiation and exposure to radon. Qualitative assessment of exposure to thorium, acid mists, asbestos, coal dust, welding fumes, and other chemicals was also performed. Mean cumulative organ dose from internal uranium exposure ranged from 1.1 mGy (lung) to 6.7 μGy (pancreas). Mean cumulative external ionizing radiation dose was 13.4 mGy. Mean cumulative radon exposure was 26 working level months (WLMs). The chemical agents to which the largest numbers of study subjects were exposed were acid mists, machining fluids, and a tributyl phosphate/kerosene mixture used in the refining process.

ASSESSMENT OF RADON ASSOCIATED LIFETIME RISK IN SUPPORT TO RADIATION PROTECTION

Background and aims: Quantification of radon associated lung cancer risk is a major public health issue. Many epidemiological studies provided results on the exposure-risk relationship in miners or in the general population. Nevertheless, due to variations in the study designs, in the characteristics of the studied populations and in factors that modify the exposure-risk relationship, it is difficult to verify the coherence of published results. We present here calculations of lifetime excess absolute risks (LEAR) to compare the results of models derived from different populations when applied to the same scenario of exposure. Methods: Models derived from pooled miner studies and pooled indoor studies were applied. Background rates were those proposed by the International Commission for Radiation Protection (ICRP). Different scenarios of chronic low rate exposure were considered. A sensitivity analysis was performed to evaluate the impact of methodological choices (model, background rate, lifetime duration…). Results: Based on the BEIR VI model and the Czech-French model, a LEAR of about 5 10-4 per Working Level Month (WLM) was derived. This estimate has to be compared with the value of 2.8 10-4 per WLM published in 1993 in the ICRP Publication 65. The sensitivity analysis showed that the estimated LEAR vary from 3 to 7 10-4 per WLM according to the model used. Calculations also illustrated the sensitivity of LEAR estimates to background rates. When applied to adapted scenarios, LEAR estimates obtained from miners and from indoor studies were different for less than 30%. Conclusions: LEAR estimates based on recent models derived from pooled analyses of miner data are higher than the one previously considered by the ICRP. Calculations demonstrate a good consistency between lung cancer risk estimates obtained from miners or indoor studies. These results provide support to the elaboration of radiation protection measures regarding radon exposure.

EFFECTS OF RADON EXPOSURE AND SMOKING ON LUNG CANCER RISK: RESULTS OF A EUROPEAN COMBINED ANALYSIS AMONG URANIUM MINERS

Background and aims: Three case-control studies nested in the French, German and Czech cohorts of uranium miners were conducted in the frame of the Alpha-Risk European research project. These studies aimed at investigating the combined effects of radon and smoking on lung cancer risk. A pooled analysis of individual data of the three studies is presented. Methods: The pooled data set includes 1476 cases and 3389 matched controls. Cumulated radon exposure during employment was obtained from measurements or a job exposure matrix. Smoking habits were determined from medical archives and questionnaires. Analysis was performed by conditional logistic regression using a linear excess relative risk model. Results: Smoking status was established for 1046 cases and 2492 controls. Ninety four percent of cases and 76% of controls were ex- or current smokers. Mean five-year lagged cumulated radon exposure was 335 Working Level Months (WLM) for cases and 211 WLM for controls. The excess relative risk per 100 WLM adjusted for smoking was 0.79 (95% confidence-interval: 0.44-1.41). Lung cancer excess relative risk was higher among non-smokers than among smokers and the results suggest a sub-multiplicative interaction between smoking and radon exposure on lung cancer mortality risk. Conclusions: This collaborative study is the largest uranium miner case-control study on lung cancer with smoking information in Europe. It confirms the persistence of radon effect on lung cancer risk when smoking is taken into account. The results are consistent with a sub-multiplicative interaction between radon and smoking and even among never smokers, the lung cancer risk is significantly associated with radon.

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%).

Lung cancer risk and radon exposure in a cohort of iron ore miners in Malmberget, Sweden

ObjectivesLung cancer caused by radon in miners is a well-known risk. However, the risk estimates vary between studies and between mines. We have studied the dose response–relationship in a Swedish...

Lung Cancer Risk from Radon and Progeny and Statement on Radon

Recent epidemiological studies of the association between lung cancer and exposure to radon and its decay products are reviewed. Particular emphasis is given to pooled case-control studies of residential exposures, and to cohorts of underground miners exposed to relatively low levels of radon. The residential and miner epidemiological studies provide consistent estimates of the risk of lung cancer, with significant associations observed at average annual concentrations of approximately 200 Bq/m³ and cumulative occupational levels of approximately 50 working level months (WLM), respectively. Based on recent results from combined analyses of epidemiological studies of miners, a lifetime excess absolute risk of 5 × 10⁻⁴ per WLM [14 × 10⁻⁵ per (mJh/m³)] should now be used as the nominal probability coefficient for radon- and radon-progeny-induced lung cancer, replacing the previous Publication 65 (ICRP, 1993) value of 2.8 × 10⁻⁴ per WLM [8 × 10⁻⁵ per (mJh/m³)]. Current knowledge of radon-associated risks for organs other than the lungs does not justify the selection of a detriment coefficient different from the fatality coefficient for radon-induced lung cancer. Publication 65 (ICRP, 2003) recommended that doses from radon and its progeny should be calculated using a dose conversion convention based on epidemiological data. It is now concluded that radon and its progeny should be treated in the same way as other radionuclides within the ICRP system of protection; that is, doses from radon and its progeny should be calculated using ICRP biokinetic and dosimetric models. ICRP will provide dose coefficients per unit exposure to radon and its progeny for different reference conditions of domestic and occupational exposure, with specified equilibrium factors and aerosol characteristics.

Mortality from circulatory system diseases and low-level radon exposure in the French cohort study of uranium miners, 1946–1999

The few studies examining the risk of circulatory system diseases (CSD) associated with ionizing radiation have reported inconsistent results. Radon, a known pulmonary carcinogen, emits ionizing radiation. The aim of this study was to examine CSD mortality in a French cohort of uranium miners and evaluate the plausibility of an association with radon exposure. The cohort included men employed as uranium miners for >/=1 year between 1946-1990. We obtained vital status and cause of death from national registers and reconstructed radon exposure for each year. Exposure--risk relations were estimated with a linear excess relative risk (ERR) model using a 5-year lag time. The cohort comprised 5086 miners, followed up for a mean duration of 30.1 years. The average cumulative exposure of the radon-exposed miners was 36.6 working level months (WLM). A total of 1411 deaths were observed, including 319 deaths due to CSD. No excess risk was found for this overall cause of death. A significant positive trend was observed between deaths from cerebrovascular diseases (CeVD) and cumulative radon exposure, together with a significant ERR per 100 WLM [ERR per 100 WLM 0.49, 95% confidence interval (95% CI) 0.07-1.23)]. Hard physical activity was identified as a potential modifying factor of the exposure-risk relation. For the first time in a cohort of uranium miners, our results suggest an association between CeVD mortality and cumulative radon exposure. Due to a lack of data, which limited our ability to assess possible confounding by cardiovascular risk factors, these findings should be interpreted with caution.

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.

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.

Proteomic Analysis of Lung Tissue of Rats Exposed to Cigarette Smoke and Radon

This study examined the protein expression in lung tissues of rats exposed to radon and cigarette smoke using a proteomic approach. Male Wistar rats were exposed daily to radon at a concentration of 100,000 Bq/m3 for 16 h, and then exposed to 20% cigarette smoke for 1 h for a period of 75 d, with the radon cumulative dose reaching 200 WLM (working level months). Proteins from rat lung tissue were separated by two-dimensional gel electrophoresis (2-DE), stained with Coomassie blue, and analyzed with ImageMaster two-dimensional (2D) platinum software. Differentially expressed proteins were analyzed by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MALDI–time of flight [TOF] MS or MALDI TOF/TOF-MS). Twenty prominent proteins that were correlated with signal transduction, metabolism, heat shock and stress, and cytoskeleton construction were identified. Some of the differential expression proteins were verified by Western blot analysis and immunohistochemical staining, and the results were consistent with 2-DE analysis. The identified proteins and peptides might be potential diagnostic markers of lung impairment induced by radon and cigarette smoke exposure.

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.

Dose conversion of radon exposure according to new epidemiological findings

In 1993, ICRP-65 recommended that dose conversion of radon exposure should be based on the comparison of detriments between radon exposure and effective dose. The lifetime detriment from the radon exposure was projected according to the epidemiological studies of uranium miners then available. The projection model (GSF) was multiplicative with temporal and age-at-exposure modification. Since 1993, new studies of uranium miners have appeared and many original studies were updated. In addition, projections of the risk have been improved by including further modifying factors as for instance in BEIR VI. New analyses were completed in the Czech and French studies of uranium miners with accurate estimates of exposures based on extensive radon measurements. The resulting estimates of excess absolute lifetime risk per unit exposure in working level months (WLM) from these models lead to dose conversion of 10 mSv WLM(-1) for the BEIR VI model and 8 mSv WLM(-1) for the joint Czech-French model in contrast to the conversion of 5 mSv WLM(-1) for the GSF model.

Radon carcinogenesis: risk data and cellular hits

Abundant epidemiological data are now available (2008) on the human lung cancer response for lifetime radon gas exposure to residential concentrations of 100 Bq m(-3), equal to 22 working level months over 40 y. We combined published pooled epidemiological data and dosimetric calculations of alpha particle hits to target basal or mucous cell nuclei in bronchial epithelium. This yields an estimate that about 10,000 basal nuclei (target) cell hits per cm2 per person over a lifetime are involved in radon-related lung cancer. The DNA target cell area (cross section) for a hit is about 2 bp. The present epidemiology indicates that 1000 persons need to be exposed to this hit rate for observable cancers to be detected. The mechanism proposed is that the extensive prior DNA damage in smokers, followed by alpha particle damage to a critical site in checkpoint genes, accounts for the greater lung cancer response in smokers.

Cytogenetic effects of radon inhalation

The effect of radon inhalation on the bone marrow cells was studied including chromosomal aberration, mitotic activity of marrow cells and the formation of micronuclei in red blood cell. Swiss albino mice were exposed to well-characterized radon doses from a pitchblende powder source placed inside the exposure radon chamber. The accumulated radon doses received by the animals ranged from 13.01 to 65.05 working level month (WLM) and were taken over 5–25 weeks. The results indicated the formation of different types of structural chromosomal aberrations, where chromosomal and chromatid breaks had the dominant incidence. The damaging effect of radon in the blood and bone marrow was expressed as a reduction in the mitotic index and an increase in chromosome damage. The chromosome damage was measured as either micronuclei in the blood or as chromosome aberrations in mitotic cells of the bone marrow.

Radon-Induced Proteomic Profile of Lung Tissue in Rats

The aim of this study was to investigate the differential expression of proteins in lung of rats following long-term exposure to radon. The total proteins of lung tissue from Wistar rats exposed to radon for cumulative doses up to 100, 200, or 400 WLM (working level months) were isolated by two-dimensional electrophoresis (2-DE) and analyzed with ImageMaster 2D Platinum software. Comparison of the 2-DE images between the control and radon-exposed groups resulted in 14 upregulated and 9 downregulated protein spots, of which 15 were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) or matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). The simultaneous up-expressions of RAGE and S100A6 indicated that both proteins might be applied as biomarkers for lung injury induced by long-term radon exposure.

Estimation of radon exposures to workers at the Fernald Feed Materials Production Center 1952–1988

The Feed Materials Production Center (FMPC) at Fernald, Ohio produced uranium metal products for use in Department of Energy defense programs. Radium-contaminated waste material was stored on-site in two K-65 silos on the west side of the facility and provided a source of 222Ra. The initial objective of this study was to estimate radon exposures to employees at FMPC working from 1952 to 1988. A modified Gaussian plume model was used to estimate exposures to workers. In an effort to validate these model-based estimates, we used 138 CR-39 film assays from window glass sampled in buildings throughout the site. Results from the CR-39 assays indicated a second substantial source of radon, the smaller Q-11 silos located in the production area. A response-surface regression analysis using a cubic spline model was fit to the CR-39 data to estimate 210Po surface activity levels at geographic coordinates throughout the facility. Knowledge of the age of the glass, the amount of contaminated waste in the Q-11 silos, and 210Po decay rates were used to estimate annual exposures to radon decay products (WLM: working level months). Estimated WLM levels associated with the Q-11 source term indicated that employees working in the vicinity during the period when they were filled with radium-contaminated waste (1952-1958) received substantially higher radon exposures than those from the K-65 source during this period. Results of the two models, corresponding to the K-65 and Q-11 sources, were combined to estimate WLM levels by year for each of the 7143 Fernald workers during the period 1952-1988. Estimated cumulative exposures to individual workers ranged from <0.5 to 751 WLM. Estimated radon exposures from this newly discovered source have important implications for future epidemiologic studies of lung cancer in workers at the Fernald facility.

Lung cancer in French uranium miners: radon-associated risk at low exposure rate and modifying effects

Introduction The association between the cumulative radon exposure and the increase risk of death from lung cancer has been well documented in underground miners exposed to radon studies. However, a better understanding of the effect of low exposure and factors modifying the lung cancer risk is of continued interest. Compared to other miners cohorts, the French cohort is characterised by a high quality of exposure assessment and low levels of exposure. We present here a new analysis which allowed to study modifying factors among the French cohort followed up to 1999. Methods The cohort includes men employed for at least one year between 1946 and 1990. Vital status and cause of death were obtained for each miner. Radon exposure was estimated individually for each year. Before 1956, the exposure was reconstructed retrospectively by a experts group and after 1955, the exposure was recorded individually. Standardized mortality ratios (SMRs) were computed using national mortality rates as references. The relationship between radon exposure and risk of lung cancer was estimated using excess relative risk models (ERR), which allow investigation of time dependent modifying factors such as period of exposure, time since exposure, duration of exposure and exposure rate. Results The cohort comprises 5,086 miners with a mean duration of follow-up of 30 years. The number of radon exposed miners is 4,133 with an average cumulative radon exposure of 36.5 Working Level Month (WLM). Mean positive annual exposure before 1956 and after 1955 was 21.3 and 1.7 WLM respectively. A total of 1,471 deaths is observed among miners. The analysis confirms a significant excess risk of lung cancer death (n=159; SMR=1.4) and a significant increase in risk with cumulative radon exposure (ERR=0,58 per 100 WLM). The main modifier is the period of exposure: the ERR/WLM is ten times higher after than before 1956. The decrease in risk with time since exposure and exposure rate disappears when period of exposure is taken into account. Conclusion This analysis confirms that the relationship between radon exposure and lung cancer risk differs according to period of exposure. Better precision in exposure estimates after 1956 may explain this difference. Continuation of this work is included in a European collaborative research project, aiming to a synthesis of the effects of radon at low levels of exposures. This work was partly supported by AREVA-NC and by the European Commission (Contract FI6R 51648).

Radon and cancers other than lung cancer in uranium miners – Results of the German uranium miner cohort study

Background It is well established that lung cancer is caused by radon, while uncertainty exists as to whether cancers other than lung might be related to exposure from radon. To investigate further the risk of extra-pulmonary cancers, mortality data from the German uranium miners cohort study are analysed. Materials and methods The cohort includes 58,747 men who were employed for at least 6 months between 1946 and 1989 at the former Wismut uranium company in Eastern Germany. Exposure to radon and its progeny, long-lived radionuclides, external gamma radiation as well as exposure to arsenic and dust was estimated by using a detailed job-exposure matrix. A total of 20.680 deaths were observed in the follow-up period 1960 to the end of 2003. The different causes of death were compared with the age- and calendar-year specific national death rates of Eastern Germany, formerly GDR. Standardized mortality ratios (SMR) with 95% confidence limits (CI) were calculated. To investigate the exposure-response relationship an internal poisson regression using a linear model was applied and the excess relative risk (ERR) per unit of cumulative exposure to radon in Working Level Month (WLM) was calculated. Results For 19.598 (94.3%) of the deceased cohort members causes of death had been available, among them 2.999 lung cancer deaths and 3.341 deaths from cancers other than lung. After adjusting for missing causes of deaths, for all cancers other than lung combined mortality in the cohort was close to that expected from national rates (SMR=1.02, 95% CI: 0.98-1.05). Among 23 individual cancer categories, statistically significant increases in mortality for cancers of the stomach (SMR=1.15, 95% CI: 1.06-1.25) and liver (SMR=1.26 , 95% CI: 1.07-1.45) and statistically significant decreases for cancers of the tongue, mouth and pharynx combined and bladder were observed. A statistically significant relation with cumulative exposure was observed for all non-lung cancers combined (ERR/WLM=0.014%) and stomach cancer (ERR/WLM=0.021%). Conclusion Our findings suggest a weak evidence for a relationship between exposure to radon and mortality from cancers other than lung cancer. Chance, confounding by unconsidered risk factors and bias due to missing causes of deaths cannot be ruled out. If at all, the risk for extrapulmonary tumors associated with radon is appreciably lower than that for lung cancer.

Lung Cancer Risk from Radon among European Uranium Miners – Modifying Effects of Time and Age at Exposure

Epidemiological evidence of lung cancer risk from radon is known since the early 1960s, when first studies on uranium miners were published. The risk was modeled in terms of relative risk in dependence on cumulated exposure. Since then, follow-up of studies has been extended, which allowed the analysis of modifying factors such as time since exposure (TSE), age at exposure (AE), attained age, and exposure rate. The present analysis was conducted in the frame of the Alpha-Risk European research program and aimed at estimating the lung cancer risk associated to radon exposure among miners with low levels of exposure and good quality of exposure assessment. The large numbers of miners included in the joint study allow a simultaneous analysis of modifying effects using exposure windows, which are appropriate in studies with protracted exposures. The analysis is based on three European cohort studies of uranium miners: Czech, French and German, including 9979, 5086 and 35084 miners, respectively. By the end of follow-up, 921, 159, and 458 lung cancer deaths were observed in these cohorts, respectively. The excess relative risks per working level month (ERR/WLM) for the three studies were 0.0116 (95%CI 0.0076-0.0157), 0.0061 (95%CI 0.0018-0.0105), and 0.0043 (95%CI 0.0028-0.0057), respectively. The different estimates are caused mainly by the so-called inverse effect of exposure rate and by quality of exposure, which both are correlated with time since exposure. We evaluated simultaneously the effects of TSE in 3 windows (5-19 years before, 20-34, 35+) and of AE in 3 windows (-29 years, 30-39, 40+). The analysis showed a strong decrease of the ERR/WLM with TSE (28% in period 20-34 years and 11% after 35 years in comparison to window 5-19). The simultaneous effect of AE was also significant: ERR/WLM for AE more than 40 years was 53% of that for AE below 30). These results will permit to improve our knowledge on the long-term risks associated to radon exposure. The present work was supported by the European Commission (Contract FI6R 516483).