Lifetime excess absolute risk for lung cancer due to exposure to radon: results of the pooled uranium miners cohort study PUMA.

The Pooled Uranium Miners Analysis (PUMA) study is the largest uranium miners cohort with 119,709 miners, 4.3 million person-years at risk and 7754 lung cancer deaths. Excess relative rate (ERR) estimates for lung cancer mortality per unit of cumulative exposure to radon progeny in working level months (WLM) based on the PUMA study have been reported. The ERR/WLM was modified by attained age, time since exposure or age at exposure, and exposure rate. This pattern was found for the full PUMA cohort and the 1960 + sub-cohort, i.e., miners hired in 1960 or later with chronic low radon exposures and exposure rates. The aim of the present paper is to calculate the lifetime excess absolute risk (LEAR) of lung cancer mortality per WLM using the PUMA risk models, as well as risk models derived in previously published smaller uranium miner studies, some of which are included in PUMA. The same methods were applied for all risk models, i.e., relative risk projection up to <95 years of age, an exposure scenario of 2 WLM per year from age 18-64 years, and baseline mortality rates representing a mixed Euro-American-Asian population. Depending upon the choice of model, the estimated LEAR per WLM are 5.38 × 10-4 or 5.57 × 10-4 in the full PUMA cohort and 7.50 × 10-4 or 7.66 × 10-4 in the PUMA 1960 + sub-cohort, respectively. The LEAR per WLM estimates derived from risk models reported for previously published uranium miners studies range from 2.5 × 10-4 to 9.2 × 10-4. PUMA strengthens knowledge on the radon-related lung cancer LEAR, a useful way to translate models for policy purposes.

Summary of the 2021 ICRP workshop on the future of radiological protection.

The International Commission on Radiological Protection (ICRP) has embarked on a process to review and revise the current System of Radiological Protection ('the System'). To stimulate discussion, the ICRP published two open-access articles: one on aspects of the System that might require review, and another on research that might improve the scientific foundation of the System. Building on these articles, the ICRP organized a Workshop on the Future of Radiological Protection as an opportunity to engage in the review and revision of the System. This digital workshop took place from 14 October-3 November 2021 and included 20 live-streamed and 43 on-demand presentations. Approximately 1500 individuals from 100 countries participated. Based on the subjects covered by the presentations, this summary is organized into four broad areas: the scientific basis, concepts and application of the System; and the role of the ICRP. Some of the key topics that emerged included the following: classification of radiation-induced effects; adverse outcome pathway methodologies; better understanding of the dose-response relationship; holistic and reasonable approaches to optimization of protection; radiological protection of the environment; ethical basis of the System; clarity, consistency and communication of the System; application of the System in medicine and application of the principles of justification and optimization of protection.

Mortality among uranium miners in North America and Europe: the Pooled Uranium Miners Analysis (PUMA).

BACKGROUND: The Pooled Uranium Miners Analysis (PUMA) study draws together information from cohorts of uranium miners from Canada, the Czech Republic, France, Germany and the USA. METHODS: Vital status and cause of death were ascertained and compared with expectations based upon national mortality rates by computing standardized mortality ratios (SMRs) overall and by categories of time since first hire, calendar period of first employment and duration of employment as a miner. RESULTS: There were 51 787 deaths observed among 118 329 male miners [SMR = 1.05; 95% confidence interval (CI): 1.04, 1.06]. The SMR was elevated for all cancers (n = 16 633, SMR = 1.23; 95% CI: 1.21, 1.25), due primarily to excess mortality from cancers of the lung (n = 7756, SMR = 1.90; 95% CI: 1.86, 1.94), liver and gallbladder (n = 549, SMR = 1.15; 95% CI: 1.06, 1.25), larynx (n = 229, SMR = 1.10; 95% CI: 0.97, 1.26), stomach (n = 1058, SMR = 1.08; 95% CI: 1.02, 1.15) and pleura (n = 39, SMR = 1.06; 95% CI: 0.75, 1.44). Lung-cancer SMRs increased with duration of employment, decreased with calendar period and persisted with time since first hire. Among non-malignant causes, the SMR was elevated for external causes (n = 3362, SMR = 1.41; 95% CI: 1.36, 1.46) and respiratory diseases (n = 4508, SMR = 1.32; 95% CI: 1.28, 1.36), most notably silicosis (n = 814, SMR = 13.56; 95% CI: 12.64, 14.52), but not chronic obstructive pulmonary disease (n = 1729, SMR = 0.98; 95% CI: 0.93, 1.02). CONCLUSIONS: Whereas there are important obstacles to the ability to detect adverse effects of occupational exposures via SMR analyses, PUMA provides evidence of excess mortality among uranium miners due to a range of categories of cause of death. The persistent elevation of SMRs with time since first hire as a uranium miner underscores the importance of long-term follow-up of these workers.

[Assessment of radon-induced health risk for occupants of a house built on uranium ore residue]. / Évaluation des risques sanitaires induits par le radon pour les occupants d'une maison construite sur des résidus de minerais d'uranium.

BACKGROUND: At the request of French public authorities, the Institute of Radiological Protection and Nuclear Safety has assessed the radiological situation of a house built on uranium ore residues in Haute-Vienne and the health risks induced from exposure to radon for all occupants. Classified as a lung carcinogen by the World Health Organization, radon is a proven cause of lung cancer in case of regular inhalation over a long period, and the risk increases with cumulative exposure. METHODS: Radon exposure was reconstructed for various standard profiles of house occupancy. A risk model derived from a European epidemiological study was used to calculate the lifetime probability of death from lung cancer according to these standard profiles. RESULTS: Risk assessment of the occupants of the house highlighted the following main findings. For a resident school child having been exposed to radon from birth to the age of 7, the lifetime relative risk (LRR) was estimated at 5. For last adult and young adult residents having lived more than 10years in the house, the probability of death from lung cancer was in the same order of magnitude as that of a regular cigarette smoker, with a LRR from 10 to 13 and a lifetime probability of death from lung cancer between 3 and 4%. If these individuals smoked regularly, in addition to being exposed to radon, this probability would be between 6 and 32% (supposing an additive or multiplicative interaction). CONCLUSION: For former occupants (non-smokers) having been exposed 10years during childhood, the LRR was two-fold lower. For children having been in day care in the house, the increased probability of death from lung cancer was low, with a LRR lower than 2. Supposing, as in adults, that the risk decreases beyond 30years after the end of radon exposure, the increase was almost zero for former occupants exposed during childhood and during day care, with a LRR close to 1.

Mortality analyses in the updated French cohort of uranium miners (1946-2007).

PURPOSE: The objectives are to analyze mortality risks in the extended follow-up of the French uranium miners' cohort and to examine their potential relation to occupational exposure to ionizing radiation (IR). METHODS: The total cohort includes 5,086 uranium miners employed in the CEA-COGEMA group and followed up from 1946 to 2007. Vital status, causes of death, and cumulative radon exposures were recorded. The post-55 subcohort includes 3,377 miners first employed after 1955, for whom long-lived radionuclides (LLR) and external gamma-ray exposure were also recorded. External mortality analyses were performed by computing standardized mortality ratios (SMR). Excess relative risks (ERRs) due to IR exposures were estimated from Poisson regression models. RESULTS: The miners included in the total cohort were followed up for 35.4 years and exposed to 36.6 working level months (WLM) on average. There was no evidence of a difference in overall mortality between miners and the general French male population. Miners had a statistically significant excess mortality rate from lung cancer (SMR = 1.34 [95% CI 1.16-1.53]) and from kidney cancer (SMR = 1.60 [1.03-2.39]). Cumulative radon exposure was significantly associated with lung cancer risk (ERR/100 WLM = 0.71 [0.31-1.30]) and cerebrovascular risk (ERR/100 WLM = 0.41 [0.04-1.03]). In the post-55 subcohort, this excess mortality from lung cancer remained associated with exposure to radon, and also with exposure to LLR and external gamma rays. CONCLUSIONS: The analyses in the extended follow-up strengthen the results previously observed among French uranium miners about their excess risk of mortality and its association with their occupational IR exposure.

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.

[Effects of chronic uranium internal exposure on mortality: results of a pilot study among French nuclear workers]. / Effets de la contamination chronique à l'uranium sur la mortalité : bilan d'une étude-pilote chez les travailleurs de l'industrie nucléaire en France.

BACKGROUND: This article presents the mortality data compiled among a cohort of workers at risk of internal uranium exposure and discusses the extent to which this exposure might differentiate them from other nuclear workers. METHODS: The cohort consisted of 2897 Areva-NC-Pierrelatte plant workers, followed from 1st January 1968 through 31st December 2006 (79,892 person-years). Mortality was compared with that of the French population, by calculating Standardized Mortality Ratios (SMR) and 95% confidence intervals (CI95%). External radiation exposure was reconstructed using external dosimetry archives. Internal uranium exposure was assessed using a plant-specific job-exposure-matrix, considering six types of uranium compounds according to their nature (natural and reprocessed uranium [RPU] and solubility [fast-F, moderate-M, and slow-S]). Exposure-effect analyses were performed for causes of death known to be related to external radiation exposure (all cancers and circulatory system diseases) and cancer of uranium target-organs (lung and hematopoietic and lymphatic tissues, HLT). RESULTS: A significant deficit of mortality from all causes (SMR=0.58; CI95% [0.53-0.63]), all cancers (SMR=0.72; CI95% [0.63-0.82]) and smoking related cancers was observed. Non-significant 30%-higher increase of mortality was observed for cancer of pleura (SMR=2.32; CI95 % [0.75-5.41]), rectum and HLT, notably non-Hodgkin's lymphoma (SMR=1.38; CI95 % [0.63-2.61]) and chronic lymphoid leukemia (SMR=2.36; CI95% [0.64-6.03]). No exposure-effect relationship was found with external radiation cumulative dose. A significant exposure-effect relationship was observed for slowly soluble uranium, particularly RPU, which was associated with an increase in mortality risk reaching 8 to 16% per unit of cumulative exposure score and 10 to 15% per year of exposure duration. CONCLUSION: The Areva-NC-Pierrelatte workers cohort presents a non-significant over-mortality from HLT cancers, notably of lymphoid origin, unrelated to external radiation exposure. The pilot study suggests an association between mortality from the HLT and lung cancers and exposure to slowly soluble RPU compounds. The results of this study should be investigated further in more powerful studies, with a dose-response analysis based on individual assessment of uranium absorbed dose to uranium-target organs.

Risk of lung cancer from radon exposure: contribution of recently published studies of uranium miners.

The International Commission on Radiological Protection (ICRP) recently estimated the risk of lung cancer associated with radon exposure, and a statement was issued in ICRP Publication 115. This was based on recent epidemiological studies and the results from a joint analysis of cohorts of Czech, French, and German uranium miners, and indicated that the excess relative risk of lung cancer per unit of exposure should be expressed with consideration of chronic exposure over more than 10 years, by modelling time since median exposure, age attained or age at exposure, and taking in account, if possible, interaction between radon and tobacco. The lifetime excess absolute risk (LEAR) calculated from occupational exposure studies is close to 5 × 10(-4) per working level month (WLM) (14 × 10(-5) per hmJ/m(3)). LEAR values estimated using risk models derived from both miners and domestic exposure studies are in good agreement after accounting for factors such as sex, attained age, and exposure scenario. A sensitivity analysis highlighted the high dependence of background mortality rates on LEAR estimates. Using lung cancer rates among Euro-American males instead of the ICRP reference rates (males and females, and Euro-American and Asian populations), the estimated LEAR is close to 7 × 10(-4) per WLM (20 × 10(-5) per hm J/m(3)).

Lung cancer mortality in the European uranium miners cohorts analyzed with a biologically based model taking into account radon measurement error.

The biologically based two-stage clonal expansion (TSCE) model is used to analyze lung cancer mortality of European miners from the Czech Republic, France, and Germany. All three cohorts indicate a highly significant action of exposure to radon and its progeny on promotion. The action on initiation is not significant in the French cohort. An action on transformation was tested but not found significant. In a pooled analysis, the results based on the French and German datasets do not differ significantly in any of the used parameters. For the Czech dataset, only lag time and two parameters that determine the clonal expansion without exposure and with low exposure rates (promotion) are consistent with the other studies. For low exposure rates, the resulting relative risks are quite similar. Exposure estimates for each calendar year are used. A model for random errors in each of these yearly exposures is presented. Depending on the used technique of exposure estimate, Berkson and classical errors are used. The consequences for the model parameters are calculated and found to be mostly of minor importance, except that the large difference in the exposure-induced initiation between the studies is decreased substantially.

Characterisation of protracted low-level exposure to uranium in the workplace: A comparison of two approaches.

Retrospective estimates of internal doses received by workers in the nuclear industry following intake of radionuclides, based on bioassay data, are a benchmark method in epidemiological studies. Nonetheless, full information relative to thousands of people included in an epidemiological cohort is rarely available, thus implying difficulties to estimate exposure precisely. To evaluate the cumulative exposure to uranium in a cohort of the AREVA NC Pierrelatte plant workers, we compared the epidemiological Job Exposure Matrix (JEM) method with the dosimetric method based on biological monitoring of exposure for 30 workers randomly selected within the cohort. A moderate to strong correlation was observed between the estimators resulting from the two approaches, thereby validating the JEM as a tool that can be used to characterise cumulative exposure to uranium in the cohort. In addition, this study showed that the JEM is a valuable complement to the interpretation of bioassy, (1) in providing information on exposure periods as well as on physical and chemical form of the radionuclides and (2) in compensating for the lack of exposure data regarding the very earliest periods. Combining the two methods may improve the precision in reconstructing cumulative exposure for epidemiological studies.

Mortality risk in the French cohort of uranium miners: extended follow-up 1946-1999.

OBJECTIVES: This paper presents the risk of death from lung cancer and from other causes of death for the French cohort of uranium miners through 1999 and estimates associations with radon exposure. METHODS: The cohort includes men employed as uranium miners for at least 1 year between 1946 and 1990. For each miner, vital status and cause of death were obtained from the national registry, and radon exposure was reconstructed for each year. Standardised mortality ratios were computed with national mortality rates as references. Exposure-risk relationships were estimated by Poisson regression, with a linear excess relative risk (ERR) model and a 5-year lag. RESULTS: The cohort included 5086 miners and 153 063 person-years of exposure. The mean duration of follow-up was 30.1 years. In all 4140 miners exposed to radon, the average cumulative exposure was 36.6 working level months (WLM). There were 1411 deaths of miners <85 years of age. The miners did not differ significantly in overall mortality from the general male population. The analysis confirmed an excess risk of lung cancer death (n = 159; SMR = 1.43; 95% CI: 1.22 to 1.68), which increased significantly with cumulative radon exposure (ERR per 100 WLM = 0.71; 95% CI: 0.29 to 1.35). The ERR per unit exposure was much higher after 1955, when the accuracy of exposure measurement improved substantially (ERR per 100 WLM = 2.00; 95% CI: 0.91 to 3.65). A significant excess of kidney cancer deaths was observed (n = 20; SMR = 2.0; 95% CI: 1.22 to 3.09), which was not associated with cumulative radon exposure. No excess was observed for other causes of death, except silicosis (n = 23; SMR = 7.12; 95% CI: 4.51 to 10.69). CONCLUSIONS: The analysis confirmed the excess risk of death from lung cancer associated with low radon exposure. An excess risk of death from kidney cancer was also observed, apparently not associated with cumulative radon exposure.

Lung cancer risk in the French cohort of uranium miners.

The French cohortof uranium miners includes 5098 miners,and 125 lung cancer deaths have been observed. The relationship between radon exposure and risk of lung cancer is estimated using relative risk models, which allow investigation of time dependent modifying factors such as the period of exposure, time since exposure and exposure rate. A linear exposure-response relationship is observed. The main modifier is the period of exposure before or after 1956: the excess relative risk after introduction of ventilation in the French mines is eight times higher than before. The decrease in risk with time since exposure and exposure rate disappears when period of exposure is taken into account. Compared to most of the uranium miner studies, this cohort constitutes a population exposed to low levels and low rates of radon for a long duration. The extension of the French cohort leads to an important increase in its statistical power. Exposure rate effect will be further investigated, in the framework of a European collaborative research project aiming at the synthesis of the effects of radon exposure at low dose and low dose rate.