CANCER INCIDENCE AND MORTALITY AMONG URANIUM MINERS IN THE PŘÍBRAM REGION OF THE CZECH REPUBLIC

There is strong evidence that radon is carcinogenic to humans, and the positive relationship between radon exposure and lung cancer mortality has been demonstrated among several cohorts of uranium miners. However, information is lacking on radon-cancer dose-response relationship at low level exposures, differences between cancer incidence and mortality, the joint effects of smoking and radon, and risks associated with radon exposure and cancers other than lung. To better understand cancer incidence and mortality among miners occupationally-exposed to low levels of radon progeny, we analyzed data for uranium miners in the Příbram region of the Czech Republic. A total of 16,434 male employees who worked at least 12 months underground between 1949 and 1991, and were alive and residing in Czechoslovakia at the start of the Czech cancer registry (1/1/1977), were included in the cohort. The case-cohort data included more precise radon exposure estimates and smoking information. Standardized mortality and incidence ratios were calculated. Expected disease rates were based on age- and calendar period-specific national mortality and cancer incidence rates. For internal analyses, the association between cumulative radon exposure and cancers was modeled using log-linear rate and linear excess relative rate models We observed a 52% increase in deaths from all malignant causes compared to expected rates. Miners had higher rates of death than expected due to lung and extrathoracic cancer. Higher than expected incidence was observed for lung, stomach, rectal, liver, extrathoracic, and some hematopoietic cancers. Positive associations were observed between radon and lung cancer incidence along with modification by smoking. The ERR/100WLM was 0.12 (95%CI: -0.09, 0.33) among non-smokers and 1.34 (95%CI: 0.88, 1.80) among smokers. Associations between cumulative radon exposure and extrathoracic cancer incidence (ERR/100 WLM = 0.07; 95%CI: -0.17, 0.31) and chronic lymphocytic leukemia (ERR/100 WLM = 0.24; 95%CI: -0.80, 1.27) were positive but imprecise. Consistent with other published studies of uranium miners, we observed positive associations between radon exposure, and lung cancer and the joint effect of smoking and radon exposure is greater than additive. Further investigation of associations between radon and extrathoracic cancer and chronic lymphocytic leukemia are needed to estimate more precise exposure-response associations.Doctor of Philosoph

Use of Anticoagulant Rodenticides in Single-Family Neighborhoods Along an Urban-Wildland Interface in California

Urbanization poses many threats for many wildlife species. In addition to habitat loss and fragmentation, non-target wildlife species are vulnerable to poisoning by rodenticides, especially acutely toxic second generation anticoagulant rodenticides (SGARs). Although such poisonings are well documented for birds and mammals worldwide, the pathways by which these widely available compounds reach non-target wildlife have not been adequately studied, particularly in urban landscapes. Long-term studies of wild carnivores in and around Santa Monica Mountains National Recreation Area, a national park north of Los Angeles, have documented \u3e85% exposure to anticoagulant rodenticides among bobcats, coyotes, and mountain lions. To investigate potential mechanisms of transfer of chemicals from residential users of rodenticides to non-target wildlife in the Santa Monica Mountains in Los Angeles County, California, we distributed surveys to residents in two study areas on the north (San Fernando Valley) and south (Bel Air-Hollywood Hills) slopes of these mountains. We assessed knowledge of residents about the environmental effects of rodenticides, and for information about individual application of chemicals. We asked for the same information from pest control operators (PCOs) in both study areas. Forty residents completed the survey in the San Fernando Valley area, and 20 residents completed the survey in Bel Air-Hollywood Hills. Despite the small number of total responses, we documented a number of important findings. Homeowners (as opposed to gardeners or PCOs) were the primary applicators of rodenticides, predominantly SGARs, and awareness of the hazards of secondary poisoning to wildlife was not consistent. Some residents reported improperly applying rodenticides (e.g., exceeding prescribed distances from structures), and in one instance a respondent reported observing dead animals outside after placing poison inside a structure. Improper application of SGARs that ignores label guidelines occurs in neighborhoods along the urban–wildland interface, thereby providing a transmission pathway for chemical rodenticides to reach native wildlife. Moreover, the responses suggest that even on-label use (e.g. placing poisons inside) can create risk for non-target wildlife

Nonmalignant respiratory disease mortality in male Colorado Plateau uranium miners, 1960-2016.

BACKGROUND: To evaluate trends of nonmalignant respiratory disease (NMRD) mortality among US underground uranium miners on the Colorado Plateau, and to estimate the exposure-response association between cumulative radon progeny exposure and NMRD subtype mortality. METHODS: Standardized mortality ratios (SMRs) and excess relative rates per 100 working level months (excess relative rate [ERR]/100 WLM) were estimated in a cohort of 4021 male underground uranium miners who were followed from 1960 through 2016. RESULTS: We observed elevated SMRs for all NMRD subtypes. Silicosis had the largest SMR (n = 52, SMR = 41.4; 95% confidence interval [CI]: 30.9, 54.3), followed by other pneumoconiosis (n = 49, SMR = 39.6; 95% CI: 29.6, 52.3) and idiopathic pulmonary fibrosis (IPF) (n = 64, SMR = 4.77; 95% CI 3.67, 6.09). SMRs for silicosis increased with duration of employment; SMRs for IPF increased with duration of employment and calendar period. There was a positive association between cumulative radon exposure and silicosis with evidence of modification by smoking (ERR/100 WLM≥10 pack-years  = 0.78; 95% CI: 0.05, 24.6 and ERR/100 WLM<10 pack-years  = 0.01; 95% CI: -0.03, 0.52), as well as a small positive association between radon and IPF (ERR/100 WLM = 0.06, 95% CI: 0.00, 0.24); these associations were driven by workers with prior employment in hard rock mining. CONCLUSIONS: Uranium mining workers had excess NMRD mortality compared with the general population; this excess persisted throughout follow-up. Exposure-response analyses indicated a positive association between radon exposure and IPF and silicosis, but these analyses have limitations due to outcome misclassification and missing information on occupational co-exposures such as silica dust

Lung and extrathoracic cancer incidence among underground uranium miners exposed to radon progeny in the Příbram region of the Czech Republic: a case-cohort study.

OBJECTIVES: Radon is carcinogenic, but more studies are needed to understand relationships with lung cancer and extrathoracic cancers at low exposures. There are few studies evaluating associations with cancer incidence or assessing the modifying effects of smoking. METHODS: We conducted a case-cohort study with 16 434 underground uranium miners in the Czech Republic with cancer incidence follow-up 1977-1996. Associations between radon exposure and lung cancer, and extrathoracic cancer, were estimated with linear excess relative rate (ERR) models. We examined potential modifying effects of smoking, time since exposure and exposure rate. RESULTS: Under a simple ERR model, assuming a 5-year exposure lag, the estimated ERR of lung cancer per 100 working level months (WLM) was 0.54 (95% CI 0.33 to 0.83) and the estimated ERR of extrathoracic cancer per 100 WLM was 0.07 (95% CI -0.17 to 0.72). Most lung cancer cases were observed among smokers (82%), and the estimated ERR of lung cancer per 100 WLM was larger among smokers (ERR/100 WLM=1.35; 95% CI 0.84 to 2.15) than among never smokers (ERR/100 WLM=0.12; 95% CI -0.05 to 0.49). Among smokers, the estimated ERR of lung cancer per 100 WLM decreased with time since exposure from 3.07 (95% CI -0.04 to 10.32) in the period 5-14 years after exposure to 1.05 (95% CI 0.49 to 1.87) in the period 25+ years after exposure. CONCLUSIONS: We observed positive associations between cumulative radon exposure and lung cancer, consistent with prior studies. We observed a positive association between cumulative radon exposure and extrathoracic cancers, although the estimates were small. There was evidence that the association between radon and lung cancer was modified by smoking in a multiplicative or super-multiplicative fashion

Mortality among workers in the Pooled Uranium Miners Analysis (PUMA)

International audienceBackground: 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

An international cohort of uranium miners: The Pooled Uranium Miners Analysis (PUMA)

International audienceIntroduction: Previous individual and pooled epidemiological studies of underground miners have provided clear evidence that increased risk of lung cancer death is associated with higher cumulative radon exposure. These studies contributed to radiation protection measures limiting exposure to radon and its short-lived progeny at higher levels. However, questions remain regarding the risk of lung cancer associated with chronic exposure to lower levels of radon present in occupational and environmental settings. Furthermore, knowledge gaps for the risks of cancers other than lung and of non-cancer diseases, such as circulatory and respiratory system diseases remain. Therefore, the setting up of a large combined cohort gathering some of the most informative cohorts of uranium miners will allow us to conduct additional epidemiological analyses with increased statistical power and harmonized methods. Methods: The Pooled Uranium Miners Analysis (PUMA) combines seven cohorts of uranium miners: three European cohorts (Czech Republic, France and Germany), two Canadian cohorts (Eldorado and Ontario cohorts) and two U.S. cohorts (Colorado Plateau and New Mexico cohorts). All included miners have available data on demographic and employment history information, vital status (date of death, and cause of death), and annual estimates of radon exposure. Some cohorts also have individual information on smoking history and/or external gamma radiation exposure. Results: The PUMA study includes 124,507 uranium miners, corresponding to 4.51 million person-years of observation. In total, 54,462 deaths were observed, including 17,085 deaths due to all sites of cancer, 7,825 deaths due to lung cancer, 18,416 deaths due to circulatory diseases and 4,621 deaths due to respiratory system diseases. The mean durations of the follow-up of individual cohorts range from 30 to 39 years. The mean cumulative exposure to radon varied from 31 to 580 Working Level Months (WLM). Planned research topics include analyses of associations between radon exposure and mortality due to lung cancer, cancers other than lung, non-malignant diseases, and of modifiers of these associations, and characterization of overall relative mortality excesses and lifetime risks.Conclusion: PUMA represents the largest study of uranium miners conducted to-date and provides opportunities to evaluate new research questions and to conduct analyses to assess potential long-term health risks associated with uranium mining that have greater statistical power to detect health risks at lower levels of exposure than can be achieved with any single cohort

An international cohort of uranium miners: The Pooled Uranium Miners Analysis (PUMA)

International audienceIntroduction: Previous individual and pooled epidemiological studies of underground miners have provided clear evidence that increased risk of lung cancer death is associated with higher cumulative radon exposure. These studies contributed to radiation protection measures limiting exposure to radon and its short-lived progeny at higher levels. However, questions remain regarding the risk of lung cancer associated with chronic exposure to lower levels of radon present in occupational and environmental settings. Furthermore, knowledge gaps for the risks of cancers other than lung and of non-cancer diseases, such as circulatory and respiratory system diseases remain. Therefore, the setting up of a large combined cohort gathering some of the most informative cohorts of uranium miners will allow us to conduct additional epidemiological analyses with increased statistical power and harmonized methods. Methods: The Pooled Uranium Miners Analysis (PUMA) combines seven cohorts of uranium miners: three European cohorts (Czech Republic, France and Germany), two Canadian cohorts (Eldorado and Ontario cohorts) and two U.S. cohorts (Colorado Plateau and New Mexico cohorts). All included miners have available data on demographic and employment history information, vital status (date of death, and cause of death), and annual estimates of radon exposure. Some cohorts also have individual information on smoking history and/or external gamma radiation exposure. Results: The PUMA study includes 124,507 uranium miners, corresponding to 4.51 million person-years of observation. In total, 54,462 deaths were observed, including 17,085 deaths due to all sites of cancer, 7,825 deaths due to lung cancer, 18,416 deaths due to circulatory diseases and 4,621 deaths due to respiratory system diseases. The mean durations of the follow-up of individual cohorts range from 30 to 39 years. The mean cumulative exposure to radon varied from 31 to 580 Working Level Months (WLM). Planned research topics include analyses of associations between radon exposure and mortality due to lung cancer, cancers other than lung, non-malignant diseases, and of modifiers of these associations, and characterization of overall relative mortality excesses and lifetime risks.Conclusion: PUMA represents the largest study of uranium miners conducted to-date and provides opportunities to evaluate new research questions and to conduct analyses to assess potential long-term health risks associated with uranium mining that have greater statistical power to detect health risks at lower levels of exposure than can be achieved with any single cohort

PUMA-pooled uranium miners analysis: Cohort profile

International audienceObjectives Epidemiological studies of underground miners have provided clear evidence that exposure to 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. Methods The 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. Results The 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 7,825 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 characterization of overall relative mortality excesses and lifetime risks.Conclusion PUMA 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

Cancer mortality after low dose exposure to ionising radiation in workers in France, the United Kingdom, and the United States (INWORKS): cohort study

International audienceObjective To evaluate the effect of protracted low dose, low dose rate exposure to ionising radiation on the risk of cancer.Design Multinational cohort study. Setting Cohorts of workers in the nuclear industry in France, the UK, and the US included in a major update to the International Nuclear Workers Study (INWORKS). Participants 309 932 workers with individual monitoring data for external exposure to ionising radiation and a total follow-up of 10.7 million person years. Main outcome measures Estimates of excess relative rate per gray (Gy) of radiation dose for mortality from cancer.Results The study included 103 553 deaths, of which 28 089 were due to solid cancers. The estimated rate of mortality due to solid cancer increased with cumulative dose by 52% (90% confidence interval 27% to 77%) per Gy, lagged by 10 years. Restricting the analysis to the low cumulative dose range (0-100 mGy) approximately doubled the estimate of association (and increased the width of its confidence interval), as did restricting the analysis to workers hired in the more recent years of operations when estimates of occupational external penetrating radiation dose were recorded more accurately. Exclusion of deaths from lung cancer and pleural cancer had a modest effect on the estimated magnitude of association, providing indirect evidence that the association was not substantially confounded by smoking or occupational exposure to asbestos.Conclusions This major update to INWORKS provides a direct estimate of the association between protracted low dose exposure to ionising radiation and solid cancer mortality based on some of the world’s most informative cohorts of radiation workers. The summary estimate of excess relative rate solid cancer mortality per Gy is larger than estimates currently informing radiation protection, and some evidence suggests a steeper slope for the dose-response association in the low dose range than over the full dose range. These results can help to strengthen radiation protection, especially for low dose exposures that are of primary interest in contemporary medical, occupational, and environmental settings