Lifetime excess absolute risk for lung cancer due to exposure to radon: results of the pooled uranium miners cohort study PUMA.

The Pooled Uranium Miners Analysis (PUMA) study is the largest uranium miners cohort with 119,709 miners, 4.3 million person-years at risk and 7754 lung cancer deaths. Excess relative rate (ERR) estimates for lung cancer mortality per unit of cumulative exposure to radon progeny in working level months (WLM) based on the PUMA study have been reported. The ERR/WLM was modified by attained age, time since exposure or age at exposure, and exposure rate. This pattern was found for the full PUMA cohort and the 1960 + sub-cohort, i.e., miners hired in 1960 or later with chronic low radon exposures and exposure rates. The aim of the present paper is to calculate the lifetime excess absolute risk (LEAR) of lung cancer mortality per WLM using the PUMA risk models, as well as risk models derived in previously published smaller uranium miner studies, some of which are included in PUMA. The same methods were applied for all risk models, i.e., relative risk projection up to <95 years of age, an exposure scenario of 2 WLM per year from age 18-64 years, and baseline mortality rates representing a mixed Euro-American-Asian population. Depending upon the choice of model, the estimated LEAR per WLM are 5.38 × 10-4 or 5.57 × 10-4 in the full PUMA cohort and 7.50 × 10-4 or 7.66 × 10-4 in the PUMA 1960 + sub-cohort, respectively. The LEAR per WLM estimates derived from risk models reported for previously published uranium miners studies range from 2.5 × 10-4 to 9.2 × 10-4. PUMA strengthens knowledge on the radon-related lung cancer LEAR, a useful way to translate models for policy purposes.

Mortality among uranium miners in North America and Europe: the Pooled Uranium Miners Analysis (PUMA).

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.

Miner studies and radiological protection against radon.

Fundamental estimates of radon-associated health risk have been provided by epidemiological studies of miners. In total, approximately 15 studies have been conducted worldwide since the 1960s. These results have contributed directly to radiological protection against radon. The present article summarises the main results, with a focus on analyses of miners exposed more recently, estimates of radon lifetime attributable risk, and interaction between radon and smoking. The potential for the upcoming Pooled Uranium Miner Analysis project to further improve our knowledge is discussed.

Effect of age at exposure in 11 underground miners studies.

Eleven underground miners studies evaluated the risk of lung cancer from exposure in underground mines. Nearly 68,000 miners were included in the joint study, contributing to nearly 2700 lung cancers. The resulting model of the Biological Effects of Ionizing Radiation (BEIR) VI Committee considered linear exposure response relationship, which was modified by time since exposure (TE), attained age and exposure rate. The effect of age at exposure (AE) was not explicitly evaluated. The presentation aims to show that the modifying effect of AE is substantial if time-since-exposure modification is simultaneously used in the model. When the excess relative risk per unit exposure (ERR/WLM) is adjusted for TE, the ERR/WLM corresponding to AE<15 is 0.013 and in subsequent categories decreased gradually up to the AE of 40 and more years, which was only 0.004. In comparison with the BEIR VI model, the present model predicts higher risks at younger ages and the risk decreases more rapidly.

International intercomparison of measuring instruments for radon/thoron gas and radon short-lived daughter products in the NRPI Prague.

During the 7th European Conference on Protection Against Radon at Home and at Work held in the autumn of 2013 in Prague, the second intercomparison of measuring instruments for radon and its short-lived decay products and the first intercomparison of radon/thoron gas discriminative passive detectors in mix field of radon/thoron were organised by and held at the Natural Radiation Division of the National Radiation Protection Institute (NRPI) in Prague. In total, 14 laboratories from 11 different countries took part in the 2013 NRPI intercomparison. They submitted both continuous monitors for the measurement of radon gas and equivalent equilibrium radon concentration in a big NRPI chamber (48 m3) and sets of passive detectors including radon/thoron discriminative for the measurement of radon gas in the big chamber and thoron gas in a small thoron chamber (150 dm3).

Reassessment of individual dosimetry of long-lived alpha radionuclides of uranium miners through experimental determination of urinary excretion of uranium.

Urinary excretion of uranium of 40 uranium miners was determined by the high-resolution inductively coupled mass spectrometry method. The concentration of uranium in the urine of the miners was converted to daily excretion of (238)U either under the assumption that the daily urinary excretion is 1.6 l or daily urinary excretion of creatinine is 1.7 g and compared with the excretion of (238)U calculated with a biokinetic model. Input data to the excretion model were derived from personal three- component ALGADE dosemeters, using the component for the estimation of inhalation of long-lived alpha radionuclides. Experimentally found contents of uranium in the urine of uranium miners are generally lower than the modelled ones, which means that the dosimetric approach is conservative. The uncertainty of inhalation intakes, derived from the measurements of filters from personal dosemeters, and the uncertainty of the concentration of uranium in the urine are discussed.

Short- and long-term variability of radon progeny concentration in dwellings in the Czech Republic.

In this paper, repeated measurements of radon progeny concentration in dwellings in the Czech Republic are described. Two distinct data sets are available: one based on present measurements in 170 selected dwellings in the Central Bohemian Pluton with a primary measurement carried out in the 1990s and the other based on 1920 annual measurements in 960 single-family houses in the Czech Republic in 1992 and repeatedly in 1993. The analysis of variance model with random effects is applied to data to evaluate the variability of measurements. The calculated variability attributable to repeated measurements is compared with results from other countries. In epidemiological studies, ignoring the variability of measurements may lead to biased estimates of risk of lung cancer.

Lung cancer in a Czech cohort exposed to radon in dwellings--50 years of follow-up.

The presented study reports lung cancer mortality in a cohort of 11 842 subjects exposed to high levels of radon covering the period 1961-2010. Exposure estimates were based on one year measurements of radon progeny in most houses of the study area (72%), missing values in the studied area were replaced by measurements in proxy houses (9%) and exposures outside the area (19%) were based on country radon mapping. Mean concentration of 448 Bq m(-3) in the study is higher than the country mean by a factor of 5. By 2010, a total of 293 lung cancers were observed. The risk is significantly related to cumulated exposure with ERR/100Bq m(-3) 0.11 (90%CI: 0.04 - 0.25). This value is consistent with the risk coefficients in other indoor studies and also with the risks observed among uranium miners. The present follow-up demonstrated that increased incidence of lung cancer depends mainly on exposure from previous 5-19 years. The relative risk of lung cancer in the present study derived from this model is 1.53 (90%CI: 1.39 - 1.69).

Lung cancer mortality in the European uranium miners cohorts analyzed with a biologically based model taking into account radon measurement error.

The biologically based two-stage clonal expansion (TSCE) model is used to analyze lung cancer mortality of European miners from the Czech Republic, France, and Germany. All three cohorts indicate a highly significant action of exposure to radon and its progeny on promotion. The action on initiation is not significant in the French cohort. An action on transformation was tested but not found significant. In a pooled analysis, the results based on the French and German datasets do not differ significantly in any of the used parameters. For the Czech dataset, only lag time and two parameters that determine the clonal expansion without exposure and with low exposure rates (promotion) are consistent with the other studies. For low exposure rates, the resulting relative risks are quite similar. Exposure estimates for each calendar year are used. A model for random errors in each of these yearly exposures is presented. Depending on the used technique of exposure estimate, Berkson and classical errors are used. The consequences for the model parameters are calculated and found to be mostly of minor importance, except that the large difference in the exposure-induced initiation between the studies is decreased substantially.

Dosimetric calculations for uranium miners for epidemiological studies.

Epidemiological studies on uranium miners are being carried out to quantify the risk of cancer based on organ dose calculations. Mathematical models have been applied to calculate the annual absorbed doses to regions of the lung, red bone marrow, liver, kidney and stomach for each individual miner arising from exposure to radon gas, radon progeny and long-lived radionuclides (LLR) present in the uranium ore dust and to external gamma radiation. The methodology and dosimetric models used to calculate these organ doses are described and the resulting doses for unit exposure to each source (radon gas, radon progeny and LLR) are presented. The results of dosimetric calculations for a typical German miner are also given. For this miner, the absorbed dose to the central regions of the lung is dominated by the dose arising from exposure to radon progeny, whereas the absorbed dose to the red bone marrow is dominated by the external gamma dose. The uncertainties in the absorbed dose to regions of the lung arising from unit exposure to radon progeny are also discussed. These dose estimates are being used in epidemiological studies of cancer in uranium miners.

A review of exposures to radon, long-lived radionuclides and external gamma at the Czech uranium mine.

This paper presents the results of the personal exposure monitoring conducted in the RoZná uranium mine in the Czech Republic. In this mine, which has been operated since the late 1950s, personal ALGADE dosemeters have been used since 1998. A group of 600 miners employed during the period 2000-09 has been analysed. Annual exposures to radon decay products, long-lived alpha emitters and external gamma radiation are described. These components play an essential role in the estimation of the total effective dose. The dependence of the exposures on the type of mining job is also assessed.

Interaction of radon and smoking among Czech uranium miners.

The study is based on a case-control study nested within a cohort study (11 000 miners and 1074 lung cancers). The controls were individually matched by year of birth and attained age. Smoking data were collected in person or from relatives of deceased subjects or from medical files. The study resulted in 850 cases of lung cancer with smoking data. The linear dependence of lung cancer relative risk (RR) on radon exposure adjusted for smoking was not substantially different from analyses when smoking was ignored and reflected mainly the risk among smokers. However, the excess RR per unit exposure among never smokers (70 cases) was substantially higher in comparison with that in smokers, reflecting differences in lung morphometry and clearance. The RRs from combined effects are substantially lower than the risk derived from the multiplicative model, but somewhat higher than those from the additive model. The work was supported by the Czech Ministry of Health (IGA NS 10596).

Content of uranium in urine of uranium miners as a tool for estimation of intakes of long-lived alpha radionuclides.

Uranium in the urine of 10 uranium miners (hewers), 27 members of general population and 11 family members of miners was determined by the High-Resolution ICP-MS method. Concentration of uranium in urine of the miners was converted to daily excretion of (238)U under the assumption that the daily excretion of urine is 2 l and compared with the modelled excretion of (238)U. Daily excretion of (238)U was modelled using input data from personal dosemeters from a component for measurement of intake of long-lived alpha radionuclides. A reasonable agreement between evaluated and measured values was found. The uncertainty of inhalation intakes, derived from measurements of filters from personal dosemeters, and uncertainty of concentration of uranium in urine are discussed.

Dominant position of colorectal cancer in Slovakia: the old-new problem for cancer control.

The development of colorectal cancer in former Czechoslovakia and its successor states is illustrated using recorded mortality and from 1968 incidence rates retrieved from National Cancer Registry of Slovakia. The relatively high mortality rates in Czechoslovakia around 1950 contrasted with rates seen in other countries of central, southern and particularly of eastern Europe and were more close to those recorded in affluent countries of western Europe and northern America. Despite continuous stabilisation and decrease of this cancer in high risk countries from late 1970s the unexpected and gradual rise of incidence rates of colorectal cancer was recorded in Slovakia. During the period studied incidence rates rose by an annual mean percent change of 4,2 and 2,8 in colon and 2,2 and 1,0 in rectal cancer in males and females respectively. Beginning with the year 1995 colorectal cancer is the most common cancer in this country in both genders together. Study of the development of colorectal cancer at the levels of subsites indicated the higher rates but decreasing proportion of rectal cancer and increasing proportion of cases occurring in proximal colon. The importance of this new priority in diagnostics, treatment and control programmes is stressed.

Dosimetric models used in the Alpha-Risk project to quantify exposure of uranium miners to radon gas and its progeny.

The European project Alpha-Risk aims to quantify the cancer and non-cancer risks associated with multiple chronic radiation exposures by epidemiological studies, organ dose calculation and risk assessment. In the framework of this project, mathematical models have been applied to the organ dosimetry of uranium miners who are internally exposed to radon and its progeny as well as to long-lived radionuclides present in the uranium ore. This paper describes the methodology and the dosimetric models used to calculate the absorbed doses to specific organs arising from exposure to radon and its progeny in the uranium mines. The results of dose calculations are also presented.

Dose conversion of radon exposure according to new epidemiological findings.

In 1993, ICRP-65 recommended that dose conversion of radon exposure should be based on the comparison of detriments between radon exposure and effective dose. The lifetime detriment from the radon exposure was projected according to the epidemiological studies of uranium miners then available. The projection model (GSF) was multiplicative with temporal and age-at-exposure modification. Since 1993, new studies of uranium miners have appeared and many original studies were updated. In addition, projections of the risk have been improved by including further modifying factors as for instance in BEIR VI. New analyses were completed in the Czech and French studies of uranium miners with accurate estimates of exposures based on extensive radon measurements. The resulting estimates of excess absolute lifetime risk per unit exposure in working level months (WLM) from these models lead to dose conversion of 10 mSv WLM(-1) for the BEIR VI model and 8 mSv WLM(-1) for the joint Czech-French model in contrast to the conversion of 5 mSv WLM(-1) for the GSF model.

Cost-effectiveness of countermeasures against radon in the Czech Republic: preliminary report.

The cost-effectiveness of remedial and preventive countermeasures against indoor radon in the frame of the Czech Radon Programme is preliminarily estimated, resulting in 72 700 CZK and 194 000 CZK per y of life gained by remediation and prevention, respectively, (exchange rate approximately 28 CZK/EUR).

A case-control study of lifestyle and lung cancer associations by histological types.

The objective of the study was to investigate the contribution of dietary factors and physical exercise to the variation in the risk of lung cancer and its major histological types among men and women in the Czech Republic, and reveal interactions between smoking and diet/physical exercise, if any. In a hospital based case-control study, data collected by in-person interviews from 1096 microscopically confirmed lung cancer cases (587 women, 509 men) and 2966 controls were analyzed using unconditional logistic regression stratified by appropriate factors. Among all nonsmoking women protective effects were observed for black tea (OR=0.69), among all smoking women for wine (OR=0.71), physical exercise (OR=0.64) and vitamin supplements (OR=0.71). Among all men, inverse associations were found in smokers between lung cancer risk and frequent intake of fruits (OR=0.69) or moderate intake of spirits (OR=0.64), and a direct association for fat foods (OR=1.68). Comparing the effects of diet/physical activity on lung cancer risk among nonsmokers versus smokers, interactions with smoking appeared for the intake of black tea and milk/dairy products among women, and for moderate intake of spirits in men. When the effects of diet/physical exercise on risk were analyzed by major cell types in women, the intake of wine and physical exercise were inversely associated with the risk of both adenocarcinoma and small cell cancer, the intakes of fruits and vitamin supplements were inversely associated with the risk of squamous cell cancer. In men, the intake of fat foods was directly associated with the risk of squamous cell cancer, while the frequent intake of apples was inversely associated with the risk of both squamous- and small cell cancers. In men an inverse association with the risk of squamous cell cancer was found for the intake of other fruits. These data suggest that diet/physical exercise may affect the risk of lung cancer and major cell types, and that interactions between some dietary items and smoking may occur. Lung cancer is a multifactorial disease, since smoking, its main determinant, and other environmental and lifestyle factors interact with one another and with genetic factors to cause the disease.

Interactions between smoking and other exposures associated with lung cancer risk in women: diet and physical activity.

UNLABELLED: The objective of the study is to estimate the differences in the impact of diet and physical exercise on lung cancer risk in female nonsmokers vs. smokers, and reveal interactions, if any. In a hospital based case-control study, data collected by in-person interviews from 569 female lung cancer cases and 2120 controls were analyzed using unconditional logistic regression stratifying by appropriate factors. Protective effects were observed for intake of milk/dairy products (OR=0.57, 95%CI 0.35-0.94), vegetables (OR=0.60, 95%CI 0.40-0.91), apples (OR=0.69), wine (OR=0.77), and physical exercise (OR=0.59, 95%CI 0.42-0.83) among smokers only, while no similar effects were found among nonsmokers. In contrast, the intake of black tea was associated with a protective effect (OR=0.66, 95%CI 0.47-0.94) among nonsmokers only. Comparing the effects of dietary items and physical activity on lung cancer risk among nonsmokers versus smokers, statistically significant effect modifications were found for black tea (P 0.005), and milk/dairy products (P 0.047). Borderline effect modifications emerged for physical exercise (P 0.077). CONCLUSIONS: These results indicate protective effects of some components of healthful diet and physical exercise among smokers, and of the intake of black tea among nonsmokers. The observed interactions of the impact of black tea, milk/dairy products and physical activity upon lung cancer risk in women at different levels of the smoking habit deserve further studies.

Congenital diaphragmatic hernia: onset of respiratory distress and size of the defect: analysis of the outcome in 104 neonates.

The purpose of this study was to evaluate the outcome in neonates with congenital diaphragmatic hernia (CDH) either presenting within the first 24 h of life or diagnosed prenatally. The study was particularly focused on the time of onset of respiratory distress and on the use of the Gore-Tex (GT) patch for diaphragmatic reconstruction. Records of 104 neonates with CDH were retrospectively reviewed. The data were analyzed by ANOVA, Kruskal-Wallis test or chi (2) test as appropriate. The result showed that the overall survival rate was 73.1% (76/104). Survival of operated neonates was 91.6% (76/83). Postnatally diagnosed neonates with the onset of respiratory distress within the first minute of life survived in 67%, with the onset between 2 and 10 min survived in 89%, whilst neonates with the onset of respiratory distress after l0 min survived in 100% (P = 0.007). Birth weight, gestational age, time of onset of respiratory distress and Apgar score significantly differed between survivors and nonsurvivors. Primary closure of the diaphragmatic defect was performed in 62 patients while the GT patch was used in 21 patients. The survival of patients with a large defect treated with a GT patch was lower (76.2 vs. 96.8%, P = 0.003). There was only one case of recurrence in our series with the GT patch. Survival depends on the time of onset of respiratory distress and size of the defect, both of which correlate with the degree of pulmonary hypoplasia. The term high-risk CDH is appropriate only for children with respiratory distress within the first 10 min of life and those diagnosed prenatally. The GT patch is a suitable material for the diaphragmatic reconstruction; we suppose that the recurrence is caused by incorrect attachment of the patch to the thoracic wall.