Alain Acker

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.

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.

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 β-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.

Leukemia Risk Associated with Chronic External Exposure to Ionizing Radiation in a French Cohort of Nuclear Workers

Leukemia is one of the earliest cancer effects observed after acute exposure to relatively high doses of ionizing radiation. Leukemia mortality after external exposure at low doses and low-dose rates has been investigated at the French Atomic Energy Commission (CEA) and Nuclear Fuel Company (AREVA NC) after an additional follow-up of 10 years. The cohort included radiation-monitored workers employed for at least one year during 1950–1994 at CEA or AREVA NC and followed during 1968–2004. Association between external exposure and leukemia mortality was estimated with excess relative risk (ERR) models and time-dependent modifying factors were investigated with time windows. The cohort included 36,769 workers, followed for an average of 28 years, among whom 73 leukemia deaths occurred. Among the workers with a positive recorded dose, the mean cumulative external dose was 21.7 mSv. Results under a 2-year lag assumption suggested that the risk of leukemia (except chronic lymphatic leukemia) increased significantly by 8% per 10 mSv. The magnitude of the association for myeloid leukemia was larger. The higher ERR/Sv for doses received 2–14 years earlier suggest that time since exposure modifies the effect. The ERR/Sv also appeared higher for doses received at exposure rates ≥20 mSv per year. These results are consistent with those found in other studies of nuclear workers. However, confidence intervals are still wide. Further analyses should be conducted in pooled cohorts of nuclear workers.

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.

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-Hodgkins 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.

0266 Mortality in the French cohort of nuclear workers monitored for external radiation exposure0266 Mortality in the French cohort of nuclear workers monitored for external radiation exposure

Objectives Understanding the effect of chronic low dose radiation exposure is crucial for radiation protection. This study analyses mortality of workers monitored for external radiation exposure while employed at three major French nuclear companies. Method The cohort includes all workers employed at least one year by CEA, AREVA NC or EDF between 1950 and 1994, monitored for radiation exposure and alive on 1 January 1968. The mortality follow-up was to 2004. Vital status and causes of death were obtained from national registries. Standardised mortality ratios were assessed using national rates as the reference. Results A total of 59 004 workers were followed-up for an average of 25 years. Mean age at end of follow-up was 56 years. Less than 1% of workers were lost to follow-up. 6310 deaths occurred between 1968 and 2004 including 2547 cancer deaths. A strong healthy worker effect was observed (all-cause SMR = 0.61, 95%-CI: 0.60–0.63). Significant excess mortality was observed for pleura cancer (SMR= 1.71, 95%-CI: 1.24–2.30) and for melanoma (SMR= 1.43, 95%-CI: 1.04–1.92), with no significant trend in SMRs for these outcomes across categories of cumulative radiation exposure. Conclusions This analysis of French nuclear workers confirms a healthy worker effect but also an excess risk of death from pleura cancer and melanoma. This cohort study is the most informative ever conducted in France among nuclear workers.

0194 Circulatory system disease mortality among French uranium miners

Objectives There is currently no consensus for an association between risk of Circulatory System Diseases (CSD) and low exposure to ionising radiation. The aim is to study the relationship between CSD mortality and radon exposure in the French cohort of uranium miners considering classical CSD risk factors. Method The French cohort includes 5086 uranium miners followed from 1946 through 2007. Among the 1935 deaths, 442 were from CSD, including 167 cases of IHD and 105 cases of CVD. Annual radon exposures were assessed individually. A nested case-control study was performed to collect individual information concerning classical CSD risk factors (weight, height, smoking status, blood pressure, blood glucose and cholesterolemia) from medical files for 76 cases of death from CSD (including 26 from IHD and 16 from CVD) and 237 controls, matched for attained age and birth date and counter-matched for cumulative radon exposure. Results In the whole cohort, a significant association with cumulative radon exposure was observed for CVD mortality, but not for CSD or IHD mortality. In the case-control study, no significant unadjusted Odd-Ratio for cumulative radon exposure was observed for any endpoint. Analyses adjusted on CSD risk factors, for which missing data do not exceed 25%, are ongoing. Conclusions The issue of CSD associated to ionising radiation is crucial for radiation protection. The present study, allowing to consider individual data on major classical CSD risk factors, will contribute to improve knowledge on the effects of low dose exposure.