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The use of ionising radiation (IR) for medical diagnosis and treatment procedures has had a major impact on the survival of paediatric patients. Although the benefits of these techniques lead to efficient health care, evaluation of potential associated long-term health effects is required. HARMONIC aims to better understand the increased risk of cancer and non-cancer effects after exposure to medical IR in children with cancer treated with modern external beam radiotherapy (EBRT) – radiation energy in MeV range – and in children with cardiac defects diagnosed and treated with cardiac fluoroscopy procedures (CFP) – radiation energy in keV range. The project investigates, among survivors of paediatric cancer, potential endocrine dysfunction, cardiovascular and neurovascular damage, health-related quality of life and second (and subsequent) primary cancer (SPC). The cardiac component builds a pooled cohort of approximately 90 000 paediatric patients who underwent CFP during childhood and adolescence to investigate cancer risk following exposure to IR and explore the potential effects of conditions predisposing to cancer. HARMONIC develops software tools to allow dose reconstruction in both EBRT and CFP to enable epidemiological investigations and future optimisation of treatments. With the creation of a biobank of blood and saliva samples, HARMONIC aims to provide a mechanistic understanding of radiation-induced adverse health effects and identify potential biomarkers that can predict these effects.

International audience; A meta-analytic summary estimate of association often is calculated as an inverse variance weighted average of study-specific estimates of association. The variances of published estimates of association are derived from their associated confidence intervals under the assumptions typical of Wald-type statistics. However, in some research areas, epidemiological results typically are obtained by fitting linear excess relative rate models, and associated likelihood-based confidence intervals are often asymmetrical; consequently, reasonable estimates of variances associated with study-specific estimates of association may be difficult to infer from the standard approach based on the assumption of a Wald-type interval. We describe a novel method to derive estimates of variance for use in meta-analysis of published results obtained by fitting linear excess relative rate models. The approach is illustrated using a previously-published example of meta-analysis of epidemiological findings regarding circulatory disease following exposure to low-level ionizing radiation, and a new example of meta-analysis of epidemiological findings regarding leukemia following exposure to ionizing radiation from diagnostic procedures; and, the meta-analytic summary obtained using the proposed approach is compared to that obtained using the more classical approach to meta-analysis. Keywords: meta-analysis; cohort studies; excess relative risk; cancer Abbreviations: RR, relative rate; CI, confidence interval; ERR, excess relative rate; Sv, sievert.

BackgroundDespite reductions in exposure for workers and the general public, radon remains a leading cause of lung cancer. Prior studies of underground miners depended heavily upon information on deaths among miners employed in the early years of mine operations when exposures were high and tended to be poorly estimated.ObjectivesTo strengthen the basis for radiation protection, we report on the follow-up of workers employed in the later periods of mine operations for whom we have more accurate exposure information and for whom exposures tended to be accrued at intensities that are more comparable to contemporary settings.MethodsWe conducted a pooled analysis of cohort studies of lung cancer mortality among 57,873 male uranium miners in Canada, Czech Republic, France, Germany, and the United States, who were first employed in 1960 or later (thereby excluding miners employed during the periods of highest exposure and focusing on miners who tend to have higher quality assessments of radon progeny exposures). We derived estimates of excess relative rate per 100 working level months (ERR/100 WLM) for mortality from lung cancer.ResultsThe analysis included 1.9 million person-years of observation and 1,217 deaths due to lung cancer. The relative rate of lung cancer increased in a linear fashion with cumulative exposure to radon progeny (ERR/100 WLM=1.33; 95% CI: 0.89, 1.88). The association was modified by attained age, age at exposure, and annual exposure rate; for attained ages

ObjectivesRadon is a ubiquitous occupational and environmental lung carcinogen. We aim to quantify the association between radon progeny and lung cancer mortality in the largest and most up-to-date pooled study of uranium miners.MethodsThe pooled uranium miners analysis combines 7 cohorts of male uranium miners with 7754 lung cancer deaths and 4.3 million person-years of follow-up. Vital status and lung cancer deaths were ascertained between 1946 and 2014. The association between cumulative radon exposure in working level months (WLM) and lung cancer was modelled as the excess relative rate (ERR) per 100 WLM using Poisson regression; variation in the association by temporal and exposure factors was examined. We also examined analyses restricted to miners first hired before 1960 and with ResultsIn a model that allows for variation by attained age, time since exposure and annual exposure rate, the ERR/100 WLM was 4.68 (95% CI 2.88 to 6.96) among miners who were less than 55 years of age and were exposed in the prior 5 to ConclusionsThis new large, pooled study confirms and supports a linear exposure–response relationship between cumulative radon exposure and lung cancer mortality which is jointly modified by temporal and exposure factors.

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.

International audience; BackgroundIonizing radiation use for medical diagnostic purposes has substantially increased over the last three decades. Moderate to high doses of radiation are well established causes of cancer, especially for exposure at young ages. However, cancer risk from low-dose medical imaging is debated.ObjectiveTo review the literature on cancer risks associated with prenatal and postnatal medical diagnostic ionizing radiation exposure among children and to assess this risk through a meta-analysis.Materials and methodsA literature search of five electronic databases supplemented by a hand search was performed to retrieve relevant epidemiological studies published from 2000 to 2019, including patients younger than 22 years of age exposed to medical imaging ionizing radiation. Pooled odds ratio (ORpooled) and pooled excess relative risk (ERRpooled) representing the excess of risk per unit of organ dose were estimated with a random effect model.ResultsTwenty-four studies were included. For prenatal exposure (radiographs or CT), no significant increased risk was reported for all cancers, leukemia and brain tumors. For postnatal exposure, increased risk was observed only for CT, mostly for leukemia (ERRpooled=26.9 Gy−1; 95% confidence interval [CI]: 2.7–57.1) and brain tumors (ERRpooled=9.1 Gy−1; 95% CI: 5.2–13.1).ConclusionCT exposure in childhood appears to be associated with increased risk of cancer while no significant association was observed with diagnostic radiographs.

International audience; Background The COCCINELLE study is a nationwide retrospective French cohort set up to evaluate the risk of radiation associated cancer in patients who undergone cardiac catheterization (CC) procedures for diagnosis or treatment of congenital heart disease during childhood [1].Material and methods Children who undergone CC procedures from 01/01/2000 to 31/12/2013 before the age of 16 in one of the 15 pediatric cardiology departments which perform pediatric CC in mainland France were included. The follow-up started at the date of the first recorded CC procedure until the exit date, i.e. the date of death, the date of first cancer diagnosis, the date of the 18th birthday, or the 31/12/2015, whichever occurred first. The cohort was linked to the National Childhood Cancer Registry to identify patients diagnosed with cancer and with the French National Directory for the Identification of Natural Persons to retrieve the patients’ vital status. An external comparison was conducted using standardized incidence ratios (SIR). Breslow and Day’s approximation was used to estimate 95% confidence intervals (CI) for the SIRs [2]. Results A total of 17,104 children were included in the cohort and followed for 110,335 person-years, with 22,227 CC procedures collected. Among the patients, 81.6 % received only one procedure. Fifty-nine cancer cases were observed in the cohort. SIRs were increased for all-cancer (SIR = 3.8, 95% CI 2.9, 4.9), leukemia (SIR = 3.3, 95% CI 2.0, 5.4), lymphoma (SIR = 14.9, 95% CI 9.9, 22.5) and solid cancers excluding central nervous system tumors (SIR = 3.3, 95% CI 2.0, 5.5) compared with the general population. Conclusion Increased risks of cancer were observed. Potential explanations include shared genetic or environmental factors, immunosuppression drugs, and exposure to medical ionizing radiation procedures. The dose-response analysis between ionizing radiation doses received during CCs and cancer occurrence will allow to address this question.Keywords: Ionizing radiation, cardiac catheterization, congenital heart disease, cancerCompeting interestsThe authors declare that they have no competing of interest.References1.Baysson H, Nkoumazok B, Barnaoui S, Réhel J, Girodon B, Milani G, Boudjemline Y, Bonnet D, Laurier D, Bernier M (2015) Follow-up of children exposed to ionising radiation from cardiac catheterisation: the Coccinelle study. Radiation protection dosimetry 165:13–162.Breslow NE, Day NE (1987) Statistical Methods in Cancer Research Volume II: The Design and Analysis of Cohort Studies, IARC Scientific Publication. IARC Scientific Publication No. 82, Lyon, France: International Agency for Research on Cancer.NotesCOCCINELLE: French acronym for COhorte sur le risque de Cancer après Cardiologie INterventionnELLECC: Cardiac CatheterizationSIR: Standardized Incidence Ratios CI: Confidence IntervalsCNS: Central Nervous System

The HARMONIC project (Health Effects of Cardiac Fluoroscopy and Modern Radiotherapy in Paediatrics) is a European study aiming to improve our understanding of the long-term health risks from radiation exposures in childhood and early adulthood. Here, we present the study design for the cardiac component of HARMONIC. A pooled cohort of approximately 100,000 patients who underwent cardiac fluoroscopy procedures in Belgium, France, Germany, Italy, Norway, Spain or the UK, while aged under 22 years, will be established from hospital records and/or insurance claims data. Doses to individual organs will be estimated from dose indicators recorded at the time of examination, using a lookup-table-based dosimetry system produced using Monte Carlo radiation transport simulations and anatomically realistic computational phantom models. Information on beam geometry and x-ray energy spectra will be obtained from a representative sample of radiation dose structured reports (RDSRs). Uncertainties in dose estimates will be modelled using 2-dimensional Monte Carlo methods. The cohort will be followed up using national registries and insurance records (Germany) to determine vital status and cancer incidence. Information on organ transplantation (a major risk factor for cancer development) and/or other conditions predisposing to cancer will be obtained from national or local registries and health insurance data, depending on country. The relationship between estimated radiation dose and cancer risk will be investigated using regression modelling. Results will improve information for patients and parents and aid clinicians in managing and implementing changes to reduce radiation risks without compromising medical benefits.

International audience; Nowadays, protection standards against ionizing radiation health effects are mainly derived from the results of the epidemiological study of atomic bomb survivors in Hiroshima and Nagasaki, who were exposed externally to radiation, at high dose rate. However, exposure to ionizing radiation in the general population and in workers generally occurs as a cumulation of low doses over years (therefore, at low dose rates), and as a result of external, but also internal, exposure. Epidemiological studies in radiation workers allow studying the long-term health effects of such exposures, and are precious to assess the adequacy of current radiation protection standards against cancer. In addition, they also allow for the study of new priority research questions in radiation protection, such as potential non-cancer effects of low dose radiation. Finally, they also provide a general picture of health in populations of radiation workers, which is useful for occupational and public health expertise. This article provides an overview of epidemiological research conducted in workers of the nuclear cycle by the French Institute for Radiological Protection and Nuclear Safety (IRSN), and discusses perspectives for its future developments. © EDP Sciences 2018; À ce jour, les normes internationales de radioprotection sont essentiellement basées sur les connaissances des effets sanitaires des rayonnements ionisants issues des études de cohortes de survivants des bombardements atomiques d’Hiroshima et de Nagasaki, qui ont subi des irradiations par voie externe à forts débits de doses. Or, les expositions aux rayonnements ionisants survenant en population générale et chez certains travailleurs correspondent généralement à de faibles doses, cumulées de manière prolongée dans le temps. Ces expositions peuvent avoir lieu par irradiation externe mais aussi par contamination interne. Les études épidémiologiques chez les travailleurs du nucléaire permettent notamment de mieux caractériser les effets de ces conditions d’expositions. Elles permettent ainsi d’évaluer l’adéquation des normes de radioprotection pour protéger les travailleurs, mais également la population générale adulte, contre les risques de cancer. Par ailleurs, elles permettent d’aborder de nouveaux questionnements de recherche en radioprotection, comme les potentiels effets non cancéreux. Enfin, ces études fournissent un bilan de santé général des populations de travailleurs du nucléaire. Cet article propose une vue d’ensemble des recherches épidémiologiques menées par l’Institut de Radioprotection et de Sûreté Nucléaire (IRSN) chez les travailleurs du cycle électronucléaire en France. Il dresse également quelques perspectives de développements possibles de ces recherches.

International audience; After the extension of the French cohort of uranium miners with the inclusion of workers employed in the Jouac mines, this article seeks to describe the new Jouac cohort and to estimate mortality risks, as well as to quantify their relation to radon exposure in this extended cohort. The Jouac cohort includes 458 miners hired by the Société des Mines de Jouac between 1957 and 2001. There is no measurement of radon exposure before 1978 and so no data were available. Consequently, only the post-1977 Jouac cohort (n = 314) has been included in the French cohort, creating an extended cohort of 5400 French uranium miners followed up from 1946 to 2007. Mortality analyses computed the standardised mortality ratios (SMRs). Excess relative risks (ERRs) were assessed using Poisson regression models. No evidence of a significant excess risk of overall mortality (n = 66, SMR = 0.93; 95% CI = 0.72-1.19) or any specific mortality was observed in the Jouac cohort. In the extended cohort, overall mortality did not increase, but a significant excess of deaths was observed for all cancers (SMR = 1.11, 95% CI = 1.03-1.19), lung cancer (SMR = 1.32, 95% CI = 1.14-1.51), and kidney cancer (SMR = 1.58, 95% CI = 1.01-2.35). Cumulative exposure to radon was 3.9 working level month (WLM) and 35.1 WLM in the post-1977 Jouac and extended cohorts, respectively. Cumulative radon exposure was significantly associated with an excess risk of death from lung cancer (ERR/100 WLM = 0.73, 95% CI = 0.32-1.33) and from cerebrovascular diseases (ERR/100 WLM = 0.42 95% CI = 0.04-1.04). In conclusion, the Jouac cohort is still a young cohort and its inclusion leads to slight modifications compared to previous analyses of the French cohort. The already known relation between radon exposure and lung cancer death as well as the excess risk of death from cerebrovascular diseases persisted in the extended cohort. © 2017 IOP Publishing Ltd.

ObjectivesEpidemiological studies of underground miners have provided clear evidence that inhalation of radon decay products causes lung cancer. Moreover, these studies have served as a quantitative basis for estimation of radon-associated excess lung cancer risk. However, questions remain regarding the effects of exposure to the low levels of radon decay products typically encountered in contemporary occupational and environmental settings on the risk of lung cancer and other diseases, and on the modifiers of these associations. These issues are of central importance for estimation of risks associated with residential and occupational radon exposures.MethodsThe Pooled Uranium Miner Analysis (PUMA) assembles information on cohorts of uranium miners in North America and Europe. Data available include individual annual estimates of exposure to radon decay products, demographic and employment history information on each worker and information on vital status, date of death and cause of death. Some, but not all, cohorts also have individual information on cigarette smoking, external gamma radiation exposure and non-radiological occupational exposures.ResultsThe PUMA study represents the largest study of uranium miners conducted to date, encompassing 124 507 miners, 4.51 million person-years at risk and 54 462 deaths, including 7825 deaths due to lung cancer. Planned research topics include analyses of associations between radon exposure and mortality due to lung cancer, cancers other than lung, non-malignant disease, modifiers of these associations and characterisation of overall relative mortality excesses and lifetime risks.ConclusionPUMA provides opportunities to evaluate new research questions and to conduct analyses to assess potential health risks associated with uranium mining that have greater statistical power than can be achieved with any single cohort.

International audience; Background: The Pooled Uranium Miners Analysis (PUMA) study draws together information about workers employed in uranium mining in Canada, the Czech Republic, France, Germany, and the United States. We compared mortality in PUMA to expectations based upon national mortality rates.Methods: The cohort includes over 120,000 uranium miners and over 50,000 deaths. Vital status and cause of death were ascertained and standardized mortality ratios (SMRs) were computed; SMRs were tabulated by categories of attained age, calendar period of follow-up, duration of employment as a miner, and calendar period of first employment as a miner. Results: Overall, the miners in PUMA experienced all cause mortality rates near those for the general population (SMR=1.0; 95%CI: 1.0, 1.0). There were more deaths than expected due to cancer of the lung (SMR=1.8; 95%CI: 1.8, 1.9), larynx (SMR=1.1; 95%CI: 0.9, 1.3), and liver (SMR=1.1; 95%CI: 0.9, 1.2). Non-malignant respiratory disease mortality also was in excess in PUMA (SMR=1.1; 95%CI: 1.0, 1.2). The relative excesses of mortality due to lung cancer and non-malignant respiratory disease persisted into more recent decades of follow-up, tended to increase with duration of employment as a uranium miner, and tended to decrease with more recent year of first employment as a uranium miner. While lung cancer was elevated in all of the PUMA cohorts, the relative excess of lung cancer was greatest among US Colorado Plateau (SMR=4.7; 95%CI: 4.3, 5.1) and Czech miners (SMR=2.9; 95%CI: 2.8, 3.1), intermediate for US New Mexico (SMR=1.9; 95%CI: 1.6, 2.1) and German Wismut (SMR=1.9; 95%CI: 1.8, 1.9) miners, and smallest among French (SMR=1.3; 95%CI:1.2, 1.5), Canadian Ontario (SMR=1.3; 95%CI: 1.3, 1.4), and Canadian Eldorado (SMR=1.3; 95%CI: 1.2, 1.4) miners. Conclusions: PUMA provides evidence of excess mortality among uranium miners and underscores the importance of long term follow-up to identify the effects of occupational exposures.

Epidemiological data on cohorts of occupationally exposed uranium miners are currently used to assess health risks associated with chronic exposure to low doses of ionizing radiation. Nevertheless, exposure uncertainty is ubiquitous and questions the validity of statistical inference in these cohorts. This paper highlights the flexibility and relevance of the Bayesian hierarchical approach to account for both missing and left-censored (i.e. only known to be lower than a fixed detection limit) radiation doses that are prone to measurement error, when estimating radiation-related risks. Up to the authors’ knowledge, this is the first time these three sources of uncertainty are dealt with simultaneously in radiation epidemiology. To illustrate the issue, this paper focuses on the specific problem of accounting for these three sources of uncertainty when estimating the association between occupational exposure to low levels of γ-radiation and lung cancer mortality in the post-55 sub-cohort of French uranium miners. The impact of these three sources of dose uncertainty is of marginal importance when estimating the risk of death by lung cancer among French uranium miners. The corrected excess hazard ratio (EHR) is 0.81 per 100 mSv (95% credible interval: [0.28; 1.75]). Interestingly, even if the 95% credible interval of the corrected EHR is wider than the uncorrected one, a statistically significant positive association remains between γ-ray exposure and the risk of death by lung cancer, after accounting for dose uncertainty. Sensitivity analyses show that the results obtained are robust to different assumptions. Because of its flexible and modular nature, the Bayesian hierarchical models proposed in this work could be easily extended to account for high proportions of missing and left-censored dose values or exposure data, prone to more complex patterns of measurement error.

It is well established that high radon exposures increase the risk of lung cancer mortality. The effects of low occupational exposures and the factors that confound and modify this risk are not clear and are needed to inform current radiation protection of miners. The risk of lung cancer mortality at low radon exposures (

Author(s): Rage, Estelle; Do, Minh; Demers, Paul A; Fenske, Nora; Kreuzer, Michaela; Laurier, Dominique; Samet, Jon; Schubauer-Berigan, Mary; Sobotzki, Christina; Tomasek, Ladislav; Zablotska, Lydia; Richardson, David

International audience; Background: Cardiac catheterization procedures (CCPs) are increasingly performed in children with congenital heart diseases who have now a long life expectancy and consequently potential long term radiation-induced risks. We evaluated organ equivalent radiation doses and projected Lifetime Attributable Risks (LARs) of cancer incidence from the most frequent procedures in pediatrics: atrial septal defect (ASD) closure, patent ductus arteriosus (PDA) occlusion or pulmonary valvuloplasty. Methods: Organ equivalent doses were individually estimated for 1251 procedures performed in children aged ≤15 years at two reference catheterization centers in France in 2009-2013, based on medical records and exposure scenarios. Gender-specific LARs were projected using the RadRAT software which incorporates extended BEIR VII risk models, various sources of risk projection uncertainties and dose variability. Survival probabilities and baseline cancer risks were those of lifelong non-smokers with no reduced life expectancy due to congenital cardiac diseases.Results: Median equivalent doses were 1-4 mSv (ASD closure), 8-17 mSv (PDA occlusion), and 10 mSv (pulmonary valvuloplasty) to both the lungs and breasts depending on patient age, and ≤10 mSv to other organs. There was a large individual variability, even for a given CCP type and patient age group. Median LARs ranged between 0.3 and 1.4 (ASD closure), 0.6 and 5.0 (PDA occlusion), and 1.0 and 12.0 (pulmonary valvuloplasty) per 1000 procedures, depending on patient gender and age at treatment. These excess risks from CCP radiation exposure would represent 0.4% to 6.0% of children’ total lifetime cancer risk. For the 10% of procedures (all types combined) with highest exposures, LARs reached 4.2 per 1000 [95% Uncertainty Interval (UI): 0.8-13.1] in boys and 22.2 per 1000 (95%UI: 7.4-45.6) in girls. In boys, lung cancer accounted for 70-80% of the projected LARs whereas in girls it accounted for 20-60% and breast cancer for 30-80% of the excess risks, depending on the CCP type and patient age.Conclusion: There was a large individual variability in radiation exposure which may lead to substantial organ equivalent doses and increased cancer risks in some cases. This suggests the need for dose reporting in clinical practice to support recommendations for long term surveillance and prevention strategies.

Epidemiological studies of uranium miners helped to establish radon as a human carcinogen. However, radon remains a leading occupational cause of cancer mortality, and many workers are exposed to radon at levels at which excess risk of lung cancer has been observed in occupational cohort studies. Prior pooled studies of underground miners provided important quantitative estimates of radon-associated lung cancer risk. Recently, efforts have been undertaken to strengthen uranium miner studies to address contemporary occupational safety concerns. New cohorts of underground miners have been enumerated, existing cohorts have been expanded, and follow-up of the major cohorts of miners has been extended substantially. An international collaborative study has been undertaken to combine information from many of the world’s most informative cohort studies of uranium miners; the combined study cohort encompasses more than 1 00 000 miners. This talk will describe the major themes of this project, the goals of the collaborators and the challenges that we have encountered to-date. We will describe similarities and differences between findings from these key cohorts and identify some major gaps in current knowledge about radon’s effects on human health. Finally, we will discuss how international collaborative studies can strengthen our understanding of risks associated with occupational and environmental radon exposures.

Context The French cohort of uranium miners was set up in the 1980’s to study the risk of mortality associated with occupational ionising radiation (IR) exposure. The analyses focused on radon exposure for a long time, but the exposure to long-lived radionuclides (LLR) arising from uranium ore dust and to external gamma rays is now also considered in the latest analyses. The individual assessment of IR exposure improved over time. The aim is to present an overview of these strengthening in the frame of the estimation of lung cancer risk. Methods The French cohort includes 5,086 men employed as a miner for at least one year and followed-up for 35 years in average (1946–2007). At end of follow-up, 211 cases of lung cancer deaths were identified among the 1935 deaths. Measurement errors (ME) in radon exposure assessment were characterised according to the periods and the methods of exposure measurement (retrospective, ambient, individual assessment). Gamma rays and LLR exposures were monitored from 1956, allowing the calculation of the absorbed lung dose due to the three radiation components. Results The size of ME in radon exposure decreased from 94% in the earliest years to 10% in the recent years. In the absence of correction for ME, the assessment of the risk for lung cancer death could be attenuated by up to 60%. In terms of lung doses, radon gas and progenies contributed to 58% of the total absorbed dose and to 97% of the equivalent dose, supporting the association between lung cancer risk and radon exposure. Conclusion Currently, a new approach is underway to take ME into account by using a structural Bayesien method. Furthermore, an international collaborative analysis of active miner cohorts would improve the estimation of risks for cancer or non-cancer diseases.

The potential health impacts of chronic exposures to uranium, as they occur in occupational settings, are not well characterized. Most epidemiological studies have been limited by small sample sizes, and a lack of harmonization of methods used to quantify radiation doses resulting from uranium exposure. Experimental studies have shown that uranium has biological effects, but their implications for human health are not clear. New studies that would combine the strengths of large, well-designed epidemiological datasets with those of state-of-the-art biological methods would help improve the characterization of the biological and health effects of occupational uranium exposure. The aim of the European Commission concerted action CURE (Concerted Uranium Research in Europe) was to develop protocols for such a future collaborative research project, in which dosimetry, epidemiology and biology would be integrated to better characterize the effects of occupational uranium exposure. These protocols were developed from existing European cohorts of workers exposed to uranium together with expertise in epidemiology, biology and dosimetry of CURE partner institutions. The preparatory work of CURE should allow a large scale collaborative project to be launched, in order to better characterize the effects of uranium exposure and more generally of alpha particles and low doses of ionizing radiation. © 2016 IOP Publishing Ltd.

A workshop dedicated to cancer risks associated with low-dose internal contamination was organised in March 2011, in Paris, in the framework of the DoReMi (Low Dose Research towards Multidisciplinary Integration) European Network of Excellence. The aim was to identify the best epidemiological studies that provide an opportunity to develop a multidisciplinary approach to improve the evaluation of the cancer risk associated with internal contamination. This workshop provided an opportunity for in-depth discussions between researchers working in different fields including (but not limited to) epidemiology, dosimetry, biology and toxicology. Discussions confirmed the importance of research on the health effects of internal contamination. Several existing epidemiological studies provide a real possibility to improve the quantification of cancer risk associated with internal emitters. Areas for future multidisciplinary collaborations were identified, that should allow feasibility studies to be carried out in the near future. The goal of this paper is to present an overview of the presentations and discussions that took place during this workshop.

Author(s): Lane, Rachel; Tomasek, Ladislav; Zablotska, Lydia; Rage, Estelle; Momoli, Franco; Little, Julian

The aim of our analysis was to study the association between air pollution and asthma among adults. For this goal, a previously developed "asthma score" was used. Persons aged 25-44 yrs were randomly selected (1991-1993) and followed up (2000-2002) within the European Community Respiratory Health Survey (ECRHS I and II, respectively). The asthma score was defined from 0 to 5, based on the positive answers to the following symptoms reported for the last 12 months: wheeze/breathlessness, chest tightness, dyspnoea at rest, dyspnoea after exercise and woken by dyspnoea. Participants' home addresses were linked to outdoor modelled NO2 estimates for 2001. Negative binomial regression was used to model the asthma score. The score from ECRHS II was positively associated with NO2 (ratio of the mean asthma score (RMS) 1.23, 95% CI 1.09-1.38, for an increase of 10 microg x m(-3)). After excluding participants with asthma and symptoms at baseline, the association remained (RMS 1.25, 95% CI 1.05-1.51), and was particularly high among those reporting a high score in ECRHS II. The latter probably reflects incident cases of asthma. Our results suggest that traffic-related pollution causes asthma symptoms and possibly asthma incidence in adults. The asthma score offers an alternative with which to investigate the course and aetiology of asthma in adults.

International audience; BACKGROUND: Effects of air pollution exposure on IgE-mediated response in asthmatics are poorly investigated. The aim was to examine the relationship between air pollution concentrations and total IgE levels in adult asthmatics. METHODS: The present study relates to the 369 asthmatic adults from the French Epidemiological study on Genetics and Environment of Asthma (EGEA), with availability of data on both total serum IgE measurements and air pollution concentrations. Geo-statistical models were performed on 4 x 4 km grids to assess individual outdoor air pollution exposure. Annual outdoor concentrations of ozone (O(3)), nitrogen dioxide (NO(2)), sulphur dioxide (SO(2)), and particulate matter smaller than 10 microm size (PM(10)), and concentrations of summer ozone were assigned to subject's home address. RESULTS: The geometric mean of total IgE was 161 IU/ml and the average of O(3) exposure was 44.9 +/- 9.5 microg/m(3). Ozone concentrations were positively related to total IgE levels and an increase of 10 microg/m(3) of O(3) resulted in an increase of 20.4% (95% CI = 3.0-40.7) in total IgE levels. Adjustment for age, gender, smoking habits and previous life in the countryside did not change the results, and an increase of 19.1% (2.4-38.6) in total IgE was observed with O(3). Negative associations observed between NO(2) and total IgE levels disappeared after including O(3) in the models. Neither SO(2) nor PM(10) were correlated with total IgE levels. CONCLUSIONS: Results suggest that O(3) or related ambient pollutants may up-regulate total IgE levels among asthmatic adults.

Resume Introduction L’etude EGEA (Etude epidemiologique des facteurs Genetiques et Environnementaux de l’Asthme, l’atopie et l’hyperreactivite bronchique), une etude cas-temoins et familiale regroupant 2 048 individus, a ete initiee afin de rechercher les facteurs environnementaux et genetiques de l’asthme. Nous presentons les resultats portant sur les aspects phenotypiques et environnementaux de l’asthme severe et de l’allergie obtenus depuis 2002 dans l’etude EGEA. Methodes et Resultats Les resultats etayent le role de facteurs hormonaux dans la severite de l’asthme et certains marqueurs allergiques associes a l’asthme. Un indice de masse corporelle eleve etait associe a la severite de l’asthme chez les femmes ayant eu des regles precoces. Des associations sont apparues entre des marqueurs d’allergie (eosinophiles, IgE, atopie) et des evenements hormono-dependants chez les femmes (asthme premenstruel, menopause et contraceptifs oraux). Chez les asthmatiques, l’exposition professionnelle aux nuisances asthmogenes, le tabagisme actif et passif etaient associes a un score clinique de severite plus eleve. L’etude a mis en evidence le role protecteur de la vie a la campagne et de l’exposition aux animaux domestiques dans la petite enfance vis-a-vis de l’allergie chez l’adulte, etayant ainsi l’hypothese hygieniste. Conclusions De nouvelles hypotheses seront prochainement testees grâce a la seconde phase de l’etude actuellement en cours.

Objectives: To assess the efficacy and safety of cetuximab in the palliative treatment of patients with intrahepatic cholangiocarcinomas (CCA) unresponsive to first-line gemcitabine-oxaliplatin (GEMOX) pretreatment. Methods: Nine patients (mean age: 54 years) with recurrent or unresectable CCA (6 peripheral and 3 hilar CCA, histologically proven) resistant to GEMOX received cetuximab 400 mg/m2 on day 1 then 250 mg/m2 weekly combined with gemcitabine 1,000 mg/m2 on day 1 and oxaliplatin 85 mg/m2 on day 2, every 3 weeks. Immunohistochemical detection of epidermal growth factor receptor (EGFR) and erbB-2, as well as EGFR gene copy number were assessed. Tumor response was measured using RECIST. Results: A total of 43 cycles were given (3–8 per patient). After 6 months, CT scans revealed 1 complete response, 1 partial response, 1 stable disease and 6 patients with disease progression. Median time to tumor progression and overall survival were 4 and 7 months, respectively. All patients relapsed (mean follow-up: 17 months). In 6 patients, death was not related to treatment. Toxicity included grade 3 neutropenia (n = 1) and acne-like rash (n = 7). In 7 of the 9 patients, EGFR was highly expressed in all tumor cells without gene amplification. No expression of erbB-2 was noted. Conclusion: Even in the absence of EGFR gene amplification, cetuximab + GEMOX is a well-tolerated palliative treatment in patients with advanced CCA. Adding cetuximab circumvents tumor resistance to GEMOX.

Resume Introduction et methode L’etude francaise EGEA (etude epidemiologique des facteurs genetiques et environnementaux de l’asthme, l’hyperactivite bronchique et l’atopie) combine une etude cas-temoins et une etude familiale de cas (n = 2120) avec trois enquetes sur 20 ans. Cet article de synthese presente les travaux realises depuis 2007 (42 articles) sur la caracterisation phenotypique et l’etude de facteurs environnementaux et genetiques de l’asthme et des phenotypes associes. Resultats Les resultats epidemiologiques et genetiques confirment le caractere heterogene de l’asthme. L’âge de debut, le statut allergique et le niveau d’activite de la maladie jouent un role preponderant dans l’identification des differents phenotypes et des facteurs genetiques sous-jacents. Le role nefaste du tabagisme, des expositions a la pollution atmospherique, aux asthmogenes professionnels et aux produits de nettoyage sur la prevalence et/ou l’activite de l’asthme est etaye. La prise en compte d’interactions gene–environnement a permis d’identifier de nouveaux facteurs genetiques de susceptibilite et de preciser leur mode d’action. Conclusion L’etude EGEA participe aux avancees de la recherche en pneumologie au niveau international. Les nouvelles donnees phenotypiques, environnementales et biologiques permettront de caracteriser l’evolution a long terme de l’asthme et les facteurs associes a cette evolution.

International audience; 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. © 2014, Springer-Verlag Berlin Heidelberg.

International audience; 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.

International audience; 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. © Springer-Verlag Berlin Heidelberg 2014.

International audience; Many occupational cohort studies on underground miners have demonstrated that radon exposure is associated with an increased risk of lung cancer mortality. However, despite the deleterious consequences of exposure measurement error on statistical inference, these analyses traditionally do not account for exposure uncertainty. This might be due to the challenging nature of measurement error resulting from imperfect surrogate measures of radon exposure. Indeed, we are typically faced with exposure uncertainty in a time-varying exposure variable where both the type and the magnitude of error may depend on period of exposure. To address the challenge of accounting for multiplicative and heteroscedastic measurement error that may be of Berkson or classical nature, depending on the year of exposure, we opted for a Bayesian structural approach, which is arguably the most flexible method to account for uncertainty in exposure assessment. We assessed the association between occupational radon exposure and lung cancer mortality in the French cohort of uranium miners and found the impact of uncorrelated multiplicative measurement error to be of marginal importance. However, our findings indicate that the retrospective nature of exposure assessment that occurred in the earliest years of mining of this cohort as well as many other cohorts of underground miners might lead to an attenuation of the exposure-risk relationship. More research is needed to address further uncertainties in the calculation of lung dose, since this step will likely introduce important sources of shared uncertainty. © 2017 by Radiation Research Society.

Introduction L’exploitation de l’uranium en France a debute en 1945 et s’est termine en 2001. Certains mineurs d’uranium francais ont par ailleurs ete expatries au Niger et au Gabon a partir de 1957. Ces travailleurs ont ete exposes de facon chronique au radon. La cohorte francaise des mineurs d’uranium a ete mise en place en 1982. Recemment, le perimetre de la cohorte francaise a ete elargi avec l’inclusion des mineurs embauches dans la mine de Jouac, initialement non integree et le suivi des mineurs expatries a ete mis a jour. L’objectif est de presenter l’analyse de mortalite realisee sur ces deux populations. Methodes La cohorte elargie inclut les hommes ayant travaille au moins un an en tant que mineur d’uranium dans le groupe CEA-COGEMA. Le suivi s’etend de 1946 a 2007. En parallele, le suivi de la mortalite des mineurs francais expatries au Niger et au Gabon a ete realise entre 1957 et 2011. Le statut vital et les causes de deces ont ete recueillis aupres des registres nationaux. L’exposition annuelle au radon a ete estimee de facon individuelle pour les mineurs de la cohorte francaise. Les ratios standardises de mortalite (SMR) ont ete calcules a partir des taux nationaux de mortalite masculine et les exces de risque relatif (ERR) ont ete estimes par regression interne de Poisson pour quantifier la relation exposition-risque. Resultats La cohorte elargie inclut 5400 mineurs suivis en moyenne pendant 34,7 ans, ayant travaille pendant 16,6 ans avec une exposition moyenne au radon de 35,1 working level month (WLM). Parmi les 1956 deces recenses (97 % de causes connues), aucune augmentation significative de la mortalite toute cause n’etait observee (SMR = 1,00 IC95 % [0,96–1,05]). Un exces de risque relatif significatif associe a l’exposition au radon etait observe pour les deces par cancer du poumon (n = 211, ERR/100WLM = 0,73 [0,32–1,33]) et par maladie cerebrovasculaire (n = 105, ERR/100WLM = 0,42 [0,04–1,04]). Chez les mineurs expatries, une mortalite toute cause significativement plus faible que celle de la population generale etait observee (n = 397 ; SMR = 0,77 [0,70–0,85]) et aucun exces de mortalite par cause specifique n’etait mis en evidence. Conclusion La cohorte elargie se caracterise par une bonne qualite de suivi et confirme l’existence de risque de cancer du poumon associe au radon. Chez les mineurs expatries, un effet du travailleur sain est observe. La limite principale de cette etude repose sur le manque de donnees sur le niveau d’exposition au radon.

International audience; 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). © 2012 by Radiation Research Society.

International audience; A broad variety of methods for measurement error (ME) correction have been developed, but these methods have rarely been applied possibly because their ability to correct ME is poorly understood. We carried out a simulation study to assess the performance of three error-correction methods two variants of regression calibration (the substitution method and the estimation calibration method) and the simulation extrapolation (SIMEX) method. Features of the simulated cohorts were borrowed from the French Uranium Miners' Cohort in which exposure to radon had been documented from 1946 to 1999. In the absence of ME correction, we observed a severe attenuation of the true effect of radon exposure, with a negative relative bias of the order of 60% on the excess relative risk of lung cancer death. In the main scenario considered, that is, when ME characteristics previously determined as most plausible from the French Uranium Miners' Cohort were used both to generate exposure data and to correct for ME at the analysis stage, all three error-correction methods showed a noticeable but partial reduction of the attenuation bias, with a slight advantage for the SIMEX method. However, the performance of the three correction methods highly depended on the accurate determination of the characteristics of ME. In particular, we encountered severe overestimation in some scenarios with the SIMEX method, and we observed lack of correction with the three methods in some other scenarios. For illustration, we also applied and compared the proposed methods on the real data set from the French Uranium Miners' Cohort study. © 2012 John Wiley and Sons, Ltd.

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.

Background and aims: Uranium miners are exposed to radon gas and its short-lived progeny (RnP), long-lived radionuclides and external gamma rays. While the lung cancer risk related to radon exposur...

21 pages; International audience; BACKGROUND/OBJECTIVES: There is evidence that exposure to air pollution affects asthma, but the effect of air pollution on asthma severity has not been addressed. The aim was to assess the relation between asthma severity during the past 12 months and home outdoor concentrations of air pollution. METHODS: Asthma severity over the past 12 months was assessed in two complementary ways among 328 adult asthmatics from the French Epidemiological study on the Genetics and Environment of Asthma (EGEA) examined between 1991 and 1995. The four-class severity score integrated clinical events and type of treatment. The five-level asthma score is based only on the occurrence of symptoms. Nitrogen dioxide (NO(2)), sulphur dioxide (SO(2)) and ozone (O(3)) concentrations were assigned to each residence using two different methods. The first was based on the closest monitor data from 1991 to 1995. The second consisted of spatial models that used geostatistical interpolations and then assigned air pollutants to the geo-coded residences (1998). RESULTS: Higher asthma severity score was significantly related to the 8-hour average of ozone during April-September (O(3)-8 h) and the number of days (O(3)-days) with 8-hour ozone averages above 110 microg.m(-3) (for a 36-day increase, equivalent to the interquartile range, in O(3)-days, odds ratio 2.22 (95% confidence interval 1.61 to 3.07) for one class difference in score). Adjustment for age, sex, smoking habits, occupational exposure, and educational level did not alter results. Asthma severity was unrelated to NO(2). Both exposure assessment methods and severity scores resulted in very similar findings. SO(2) correlated with severity but reached statistical significance only for the model-based assignment of exposure. CONCLUSIONS: The observed associations between asthma severity and air pollution, in particular O(3), support the hypothesis that air pollution at levels far below current standards increases asthma severity.

Objectives The study aims to assess the risk of lung cancer death associated with lung doses due to radon gas and its short-lived progeny (RnP), long-lived radionucleides (LLR) and external γ rays in the French cohort of uranium miners. Methods The cohort included 3271 exposed miners followed from 1956 through 1999. Annual exposures were assessed individually and lung doses were calculated according to the Human Respiratory Tract Model (Publication 66 of the International Commission on Radiological Protection). Poisson regression was used to fit linear excess relative risk (ERR) models to estimate dose-risk relationships. Results The mean absorbed lung dose due to α emitters was 78 milliGray (mGy), and to non-α emitters, 56 mGy. RnP accounted for 97% of the α absorbed dose. A significant ERR of lung cancer death was associated with the total absorbed lung dose (ERR/Gy (95% CI) = 2.9 (0.8–7.5)), the α absorbed dose (4.58 (1.3–10.9)) and RnP (4.6 (1.3–11.2)). Assuming a value of 20 for the relative biological effectiveness of α particles in lung cancer induction, the ERR/Gy-equivalent for the total-weighted lung dose was 0.2 (0.1–0.5), similar to that for the α-weighted and RnP-weighted lung dose. Conclusions These first results about lung doses from the European Alpha-Risk project, with regard to the lung dose distribution, support the major role of RnP in the risk of lung cancer death.

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.