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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.

Objectives To examine the risk of death from leukaemia in relation to occupational chronic low-level external and internal radiation exposure in a cohort of 58 972 former German uranium miners with mortality follow-up from 1946 to 2013. Methods The red bone marrow (RBM) dose from low-linear energy transfer (LET) (mainly external γ-radiation) and high-LET (mainly radon gas) radiation was estimated based on a job-exposure matrix and biokinetic/dosimetric models. Linear excess relative risks (ERR) and 95% CIs were estimated via Poisson regression for chronic lymphatic leukaemia (CLL) and non-CLL. Results The mean cumulative low-LET and high-LET RBM doses among the 86% radiation-exposed workers were 48 and 9 mGy, respectively. There was a positive non-significant dose-response for mortality from non-CLL (n=120) in relation to low-LET (ERR/Gy=2.18; 95% CI −0.41 to 6.37) and high-LET radiation (ERR/Gy=16.65; 95% −1.13 to 46.75). A statistically significant excess was found for the subgroup chronic myeloid leukaemia (n=31) in relation to low-LET radiation (ERR/Gy=7.20; 95% CI 0.48 to 24.54) and the subgroup myeloid leukaemia (n=99) (ERR/Gy=26.02; 95% CI 2.55 to 68.99) for high-LET radiation. The ERR/Gy tended to be about five to ten times higher for high-LET versus low-LET radiation; however, the CIs largely overlapped. Results indicate no association of death from CLL (n=70) with either type of radiation. Conclusions Our findings indicate an increased risk of death for specific subtypes from non-CLL in relation to chronic low-LET and high-LET radiation, but no such relation for CLL.

Objective To quantify the relationship between death from non-malignant respiratory diseases (NMRD) and exposure to silica dust or radon in a cohort of 58 690 former German uranium miners. Methods In the follow-up period from 1946 to 2008, a total of 2336 underlying deaths from NMRDs occurred, including 715 deaths from chronic obstructive pulmonary diseases (COPD) and 975 deaths from silicosis or other pneumoconiosis. Exposure to respirable crystalline silica and radon was individually assessed by means of a comprehensive job-exposure matrix. Risk analyses were based on a linear Poisson regression model with the baseline stratified by age, calendar year and duration of employment. Results There was no increase in risk of death from COPDs or any other NMRDs in relation to cumulative exposure to silica (mean=5.9, max=56 mg/m 3 -years), except in the group of deaths from silicosis or other pneumoconiosis. Here, a strong non-linear increase in risk was observed. Cumulative radon exposure (mean=280; max=3224 Working Level Months) was not related to death from COPDs or any other NMRDs. Conclusions The present findings do not indicate a relationship between mortality from COPD with silica dust or radon. However, validity of cause of death and lack of control for smoking remain potential sources of bias.

Objectives The presentation includes an evaluation of lung cancer risk observed in three cohort studies of uranium miners in the Czech Republic, France, and Germany. Methods The analysis is based on a total of 1567 lung cancers observed among 50 059 uranium miners during the period 1947–99. The risk, in terms of excess relative risk per unit exposure (ERR/WLM), is analysed in dependence on time since exposure, exposure rate, age at exposure, and other modifying factors. Results and conclusions The presentation includes analyses of differences and similarities between the three cohorts when modifying factors are incorporated into the risk model. The risk coefficients in separate cohorts corresponding to low annual exposures in more recent periods are considerably consistent: ERR/WLM = 0.021, 0.022, and 0.020 in the Czech, French and German studies, respectively. The uncertainty of the pooled estimate related to such low cumulated exposures is only 14%. The relative risk decreases with time since exposure by ½ per decade, and simultaneously by ⅓ per decade of age at exposure. The work was supported by the European Commission under FP6 (FI6R 516483).

Objectives To investigate the exposure-response relationship between silica dust and lung cancer mortality within German uranium miners in the extended follow-up period from 1946 to 2008. The cohort consists of 58,672 miners including 2.2 Mio person-years and 3,477 lung cancer deaths. Methods Individual information on occupational exposure to crystalline silica in mg/m³-years and the potential confounders radon and arsenic is available for all cohort members based on a detailed job-exposure matrix. Internal Poisson regression with baseline-stratification by age and calendar year was used to estimate the excess relative risk (ERR) per mg/m³-year. Several spline functions were applied to investigate the exposure-response relationship. Detailed adjustment for cumulative radon and arsenic exposure was conducted. Effect modification by age, time and exposure-rate was tested. Additionally detailed risk analyses with specific focus on the low dose range have been performed. Results All miners were exposed to crystalline silica at any time. The mean cumulative silica exposure was 5,9 mg/m³-years with a maximum of 56 mg/m³-years. A piece-wise linear spline function with a knot at 10 mg/m³-years provided the best model fit. After full adjustment for radon (continuous variable with consideration of time since median exposure and dose rate) and arsenic no increase in risk below 10 mg/m³-years was observed. Fixing the parameter estimate of the ERR in this range at 0 provided the best model fit with an ERR of 0.065 (95% CI: 0.043, 0.087) above 10 mg/m³-years. The silica-induced lung cancer risk decreased with increasing attained age. Data of a nested case-control study did not indicate a major correlation between silica and smoking status. Conclusions The study confirms a positive exposure-response relationship between silica and lung cancer, particularly for high exposures. No clear evidence was observed in the low-dose range. Confounding by smoking is unlikely but residual confounding cannot be fully excluded.