Chest X-ray screening examinations among French uranium miners: exposure estimation and impact on radon-associated lung cancer risk.

BACKGROUND: Medical surveillance of uranium miners can include periodic chest X-ray examinations. This study aimed to assess the X-ray exposure due to occupational health monitoring in the French cohort of uranium miners, and to test whether consideration of this additional radiation exposure impacts the excess risk of lung cancer death associated with radon exposure. METHOD: X-ray exposure due to occupational health monitoring was estimated retrospectively based on review of a sample of miners' medical records and bibliographic data. Four exposure scenarios were designed, differing in their assumptions about the type of procedures performed, their frequency, and the lung dose delivered. Radon exposure and lung doses from exposure to α-particle emitters and external γ rays have previously been individually assessed. Exposure-risk and dose-risk relations were estimated by Poisson regression with a linear excess relative risk (ERR) model. RESULTS: The cohort included 5086 miners with a mean follow-up duration of 30.1 years. The mean number of chest X-ray examinations ranged from 15.1 in the lowest to 34 in the highest-exposure scenario, and produced a mean cumulative lung dose ranging from 4.6 to 34.2 mGy. The role of occupation-related imaging screening X-ray procedures in total equivalent lung dose appeared insignificant compared to α-emitter exposure. X-ray exposure was not associated with lung cancer mortality risk. The ERR associated with radon remained significantly positive when X-ray exposure was included in the multivariate analysis. CONCLUSIONS: X-ray exposure did not confound the exposure-risk relation between radon and lung cancer.

Kidney cancer mortality and ionizing radiation among French and German uranium miners.

The investigation of potential adverse health effects of occupational exposures to ionizing radiation, on uranium miners, is an important area of research. Radon is a well-known carcinogen for lung, but the link between radiation exposure and other diseases remains controversial, particularly for kidney cancer. The aims of this study were therefore to perform external kidney cancer mortality analyses and to assess the relationship between occupational radiation exposure and kidney cancer mortality, using competing risks methodology, from two uranium miners cohorts. The French (n = 3,377) and German (n = 58,986) cohorts of uranium miners included 11 and 174 deaths from kidney cancer. For each cohort, the excess of kidney cancer mortality has been assessed by standardized mortality ratio (SMR) corrected for the probability of known causes of death. The associations between cumulative occupational radiation exposures (radon, external gamma radiation and long-lived radionuclides) or kidney equivalent doses and both the cause-specific hazard and the probability of occurrence of kidney cancer death have been estimated with Cox and Fine and Gray models adjusted to date of birth and considering the attained age as the timescale. No significant excess of kidney cancer mortality has been observed neither in the French cohort (SMR = 1.49, 95 % confidence interval [0.73; 2.67]) nor in the German cohort (SMR = 0.91 [0.77; 1.06]). Moreover, no significant association between kidney cancer mortality and any type of occupational radiation exposure or kidney equivalent dose has been observed. Future analyses based on further follow-up updates and/or large pooled cohorts should allow us to confirm or not the absence of association.

Impact of chemical exposure on cancer mortality in a French cohort of uranium processing workers.

BACKGROUND: Nuclear workers may be exposed to a variety of chemical hazards, in addition to radiation. We examined the effect of chemical exposures on cancer mortality among French uranium processing workers at the AREVA NC Pierrelatte facility. METHODS: A cohort of 2,897 uranium processing workers employed for at least 6 months was followed from 1968 through 2006. Exposure to uranium and potentially carcinogenic chemicals was assessed with a plant-specific job-exposure matrix. Mortality hazard ratios (HRs) for cancers of the lung, lymphohematopoietic system, kidney and bladder, brain and central nervous system (BCNS), and prostate were estimated for each specific chemical exposure, with Cox regression models stratified for sex and calendar period and adjusted for socioeconomic status. Additional adjustments enabled us to examine the effect of co-exposure to uranium and other chemicals. RESULTS: Exposure to aromatic solvents was associated with increased risk of BCNS malignancies after adjustment for other chemicals (HR=6.53, 95% CI=1.14-37.41; n=6) and for other chemicals and uranium (HR=7.26, 95% CI=0.90-58.19) in the annual exposure status model. Selected groups of lymphohematopoietic cancers were found associated with solvent exposure. Inconclusive results were found regarding chromium (VI) exposure, since only 2 workers died from lung cancer among 109 exposed. CONCLUSION: Based on our pilot study, it seemed important to take into account chemical exposures in the analyses of cancer mortality among French uranium processing workers.

Does uranium induce circulatory diseases? First results from a French cohort of uranium workers.

OBJECTIVES: Increased risk of circulatory system diseases (CSDs) was observed in nuclear workers handling uranium and plutonium in Russia and the UK. This work examines the CSD mortality after chronic intake of uranium among 2897 workers (79,892 person-years) at a uranium processing plant (1960-2006) in France. METHODS: Cumulative exposure to different uranium compounds, classified by their isotopic composition and solubility type, was quantified on the basis of a plant-specific job-exposure matrix and individual job histories. HRs and associated 95% CI for CSD (n = 111) and specific CSD categories were estimated using Cox regression models, stratified on sex and birth cohort and adjusted for potential confounders. The effect of smoking was analysed among 260 smokers (42 CSD deaths). RESULTS: Compared to unexposed workers, CSD mortality was increased among workers exposed to slowly soluble reprocessed uranium (RPU) (HR = 2.13, 95% CI = 0.96 to 4.70) and natural uranium (HR = 1.73, 95% CI = 1.11 to 2.69). The risk increased with cumulative exposure and exposure duration. In the subgroup of smokers, the risk estimates were higher but with larger CIs: HR=1.91 (95% CI = 0.92 to 3.98) for natural uranium and HR = 4.78 (95% CI = 1.38 to 16.50) for RPU. CONCLUSIONS: The authors observed that exposure to slowly soluble uranium, namely RPU, may increase the risk of CSD mortality. However, these results are preliminary since the study is lacking statistical power and many other biological and lifestyle-related factors may cause CSD. More detailed investigations are necessary to confirm these findings and analyse in depth the effects of internal radiation exposure on the circulatory system.

Risk of lung cancer mortality in relation to lung doses among French uranium miners: follow-up 1956-1999.

The aim of this study was to assess the risk of lung cancer death associated with cumulative lung doses from exposure to α-particle emitters, including radon gas, radon short-lived progeny, and long-lived radionuclides, and to external γ rays among French uranium miners. The French "post-55" sub-cohort included 3,377 uranium miners hired from 1956, followed up through the end of 1999, and contributing to 89,405 person-years. Lung doses were calculated with the ICRP Human Respiratory Tract Model (Publication 66) for 3,271 exposed miners. The mean "absorbed lung dose" due to α-particle radiation was 78 mGy, and that due to the contribution from other types of radiation (γ and ß-particle radiation) was 56 mGy. Radon short-lived progeny accounted for 97% of the α-particle absorbed dose. Out of the 627 deaths, the cause of death was identified for 97.4%, and 66 cases were due to lung cancer. A significant excess relative risk (ERR) of lung cancer death was associated with the total absorbed lung dose (ERR/Gy = 2.94, 95% CI 0.80, 7.53) and the α-particle absorbed dose (4.48, 95% CI 1.27, 10.89). Assuming a value of 20 for the relative biological effectiveness (RBE) of α particles for lung cancer induction, the ERR/Gy-Eq for the total weighted lung dose was 0.22 (95% CI: 0.06, 0.53).

The influence of multiple types of occupational exposure to radon, gamma rays and long-lived radionuclides on mortality risk in the French "post-55" sub-cohort of uranium miners: 1956-1999.

The adverse health effects of radon on uranium miners, especially on their lungs, are well documented, but few studies have considered the effects of other radiation exposures. This study examined the mortality risks associated with exposure to radon, external γ rays and long-lived radionuclides (LLR) in the French "post-55" sub-cohort, which includes uranium miners first employed between 1956 and 1990 for whom all three types of exposure were assessed individually. Exposure-risk relationships were estimated with linear excess relative risk models and a 5-year lag time. The post-55 sub-cohort includes 3377 miners, contributing 89,405 person-years, followed up through the end of 1999 with a mean follow-up of 26.5 years. Mean cumulative exposure was 17.8 WLM for radon, 54.7 mSv for γ rays, and 1,632 Bq.m(-3).h for LLR. Among the 611 deaths observed, 66 were due to lung cancer. Annual individual exposures were significantly correlated. Increased mortality was observed for lung cancer (SMR = 1.30; 95% CI: 1.01, 1.65) and for brain and central nervous system (CNS) cancer (SMR = 2.00; 95% CI: 1.09, 3.35). Cumulative exposure to radon, γ rays and LLR was associated only with a significant risk of lung cancer. These new results could suggest an association between lung cancer and exposure to γ rays and LLR. They must nonetheless be interpreted with caution because of the correlation between the types of exposure. The calculation of organ doses received by each of these exposures would reduce the collinearity.

Cancer mortality among two different populations of French nuclear workers.

PURPOSE: The aim of this paper is to study the effect of external photon radiation on the mortality of two populations of French nuclear workers: workers exposed only to external photon radiation and workers potentially exposed also to internal contamination or to neutrons. METHOD: External photon radiation has been measured through individual dosimeters. Potential exposure to internal contamination or to neutrons has been assessed by experts on the basis of quantitative measurements or of worksite and type of activity. The mortality observed in each population was compared with that expected from national mortality statistics, by computing standardized mortality ratios. Dose-effect relationships were analyzed through trend tests and log-linear Poisson regressions. RESULTS: 14,796 workers were exposed only to external photon radiation; 14,408 workers were also potentially exposed to internal radiation or to neutrons. Between 1968 and 1994, the number of deaths is respectively, 645 and 1,197. The mean external photon dose was respectively, 3.7 and 12.9 mSv. Similar Healthy Worker Effects were observed in the two populations (SMR = 0.59). SMR of 2.41 90% CI [1.39-3.90] was observed for malignant melanoma among workers of the second population. Significant dose-effect relationships were observed: among workers exposed only to external photon radiation for leukemia except CLL and in the other population, for cancers and other diseases related to tobacco or alcohol consumption. CONCLUSIONS: Results differed between the two populations. The increase in leukemia risk with dose in the first population will have to be confirmed with extended follow-up. In the other population, results may have been confounded by alpha-emitters inhalation, tobacco, or alcohol consumption.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Multifactorial study of the risk of lung cancer among French uranium miners: radon, smoking and silicosis.

This case-control study nested in the French cohort of uranium miners provides an opportunity to take account of silicosis and smoking in the assessment of the relation between radon and lung cancer. The study includes 100 miners who died of lung cancer and 500 matched controls born within the same period of birth and of the same age at the time of death of the matching case. Data on radon exposure are obtained from individual monitoring of the miners, and data on smoking come from medical records and interviews. To identify cases of silicosis among the 600 miners surveyed, appraisals carried out as part of the compensation process for occupational diseases are used. Statistical analyses are based on a conditional logistic regression, and the linear model for excess relative risk was used to model the risk of death due to lung cancer according to cumulative radon exposure. The percentage of missing data on silicotic status is less than 20%. The study reveals a significant association between the relative risk of lung cancer and silicosis (ORsilicosis = 3.6; 95% CI: 1.4-8.9), and the relation between radon and lung cancer persists after adjusting for smoking and silicotic status (ERRradon per WLM = 1.0%; 95% CI: 0.1-3.5%). Radon, cigarette smoking and silicotic status appear to be three factors that each have a specific effect on the risk of lung cancer. This study reminds us of the complexity involved in assessing occupational risks in the case of multiple sources of exposure.

Radon-associated lung cancer risk among French uranium miners: modifying factors of the exposure-risk relationship.

Radon is classified as a known pulmonary carcinogen in humans. A better understanding of the effects of low exposure and time-dependent factors, modifying the lung cancer risk is of continued interest. We present analyses of the exposure-risk relationship in the French cohort of uranium miners updated until 1999 and including five additional years of follow-up. These new analyses provide a better opportunity to look at low radon exposures with longer follow-up intervals, and allow consideration of new modifying factors, such as physical activity, mine location and job type. The cohort includes 5,086 miners, and 159 lung cancer deaths have been observed among these over a follow-up of more than 30 years. The exposure-risk relationship was estimated using excess relative risk models, which allow investigation of several modifying factors such as period of exposure, time since exposure, age at exposure, duration of exposure, exposure rate, job type, mine type and physical activity. The analysis confirms the association between radon exposure and lung cancer risk (ERR per 100 WLM = 0.58, P < 0.01). Period of exposure and physical activity appear as major modifying factors. Higher risks are observed for hard physical activity works. The effect of hard physical activity persists when the period of exposure is taken into account (ERR per 100 WLM = 2.95, P < 0.01).