Lung Cancer Risk from Occupational and Environmental Radon and Role of Smoking in Two Czech Nested Case-Control Studies

The aim of the present study was to evaluate the risk of lung cancer from combined exposure to radon and smoking. Methodologically, it is based on case-control studies nested within two Czech cohort studies of nearly 11,000 miners followed-up for mortality in 1952–2010 and nearly 12,000 inhabitants exposed to high levels of radon in homes, with mortality follow-up in 1960–2010. In addition to recorded radon exposure, these studies use information on smoking collected from the subjects or their relatives. A total of 1,029 and 370 cases with smoking information have been observed in the occupational and environmental (residential) studies, respectively. Three or four control subjects have been individually matched to cases according to sex, year of birth, and age. The combined effect from radon and smoking is analyzed in terms of geometric mixture models of which the additive and multiplicative models are special cases. The resulting models are relatively close to the additive interaction (mixing parameter 0.2 and 0.3 in the occupational and residential studies, respectively). The impact of the resulting model in the residential radon study is illustrated by estimates of lifetime risk in hypothetical populations of smokers and non-smokers. In comparison to the multiplicative risk model, the lifetime risk from the best geometric mixture model is considerably higher, particularly in the non-smoking population

Low Radon Exposures and Lung Cancer Risk: Joint Analysis of the Czech, French and Beaverlodge Cohorts of Uranium Miners

International audienceIt 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 (< 100 working-level months) was assessed in the joint cohort analysis of Czech, French, and Canadian uranium miners, employed in 1953 or later. Statistical analysis was based on linear Poisson regression modeling with grouped cohort survival data. Two sensitivity analyses were used to assess potential confounding from tobacco smoking. A statistically significant linear relationship between radon exposure and lung cancer mortality was found. The excess relative risk per working-level month was 0.022 (95% confidence intervals: 0.013-0.034), based on 408 lung cancer deaths and 394,236 person-years of risk. Time since exposure was a statistically significant modifier; risk decreased with increasing time since exposure. A tendency for a decrease in risk with increasing attained age was observed, but this was not statistically significant. Exposure rate was not found to be a modifier of the excess relative risk. The potential confounding effect of tobacco smoking was estimated to be small and did not substantially change the radon-lung cancer mortality risk estimates. This joint cohort analysis provides strong evidence for an increased risk of lung cancer mortality from low occupational radon exposures. The results suggest that radiation protection measures continue to be important among current uranium miners

Studying biomarkers reflecting the adverse outcome pathways from exposures to diseases using molecular epidemiology: example of the molecular epidemiology protocol developed as part of the Concerted Uranium Research in Europe (CURE) project

International audienceResults produced during recent years have shown that epidemiology still has a strong potential to quantify radiation-related health effects after low dose exposures, even below 100 mGy. However below certain dose levels, which may differ according to the disease considered and population characteristics (e.g.: age at exposure), direct observations of dose-risk relationships by classical epidemiological studies are not possible. Indirect evidence, including subtle changes in various physiological functions and biomarkers (sub-clinical/ pre-pathological) reflecting key events in response to low or even very low doses will need to be determined in order to draw inferences on risk after exposures to very low doses. Such inference will be possible for instance, if very large cohorts, - which can even be non-radiation cohorts - quantify the relationships between (combinations of) these biomarkers or changes in physiological function and disease risks. Such inferences are in line with the so-called “meet-in-the-middle” approach. Following this philosophy, as part of the CURE project which aimed to prepare protocols to study the health effects of chronic uranium exposures at low dose, a rational approach was employed to select biomarkers of exposures and subclinical biomarkers of effects in uranium target organs (kidney, lung, bone, brain) and in systems in which potential effects could be suspected (e.g.: vascular system). The use of non-targeted techniques (omics) is also essential to generate new hypotheses of induced signal cascades resulting finally in disease pathways and disease onset (Adverse Outcome Pathways, AOP). A full molecular epidemiology protocol was then developed, including a questionnaire and other means of data collection to measure potential confounding factors. Such an approach will be useful in order 1) to determine the changes in biomarkers which may be attributed to uranium itself and 2) to better appreciate the relative influence of uranium versus other stressors on these biomarker changes, as part of AOP leading to chronic diseases. 3) These yet hypothetical diseases and their development can subsequently be studied in classical epidemiological approaches (at higher doses) and through well-justified radiobiological experiments. Finally, indirect evidence gained from molecular epidemiology studies will prove useful to quantify risks after very low dose exposures, in addition to experimental studies and classical epidemiology