Accounting for Berkson and Classical Measurement Error in Radon Exposure Using a Bayesian Structural Approach in the Analysis of Lung Cancer Mortality in the French Cohort of Uranium Miners.

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.

Concerted Uranium Research in Europe (CURE): toward a collaborative project integrating dosimetry, epidemiology and radiobiology to study the effects of occupational uranium exposure.

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.

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.