Radon and lung cancer in the pooled uranium miners analysis (PUMA): highly exposed early miners and all miners.

OBJECTIVES: Radon 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. METHODS: The 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 <100 WLM cumulative exposure. RESULTS: In 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 <15 years at annual exposure rates of <0.5 WL. This association decreased with older attained age, longer time since exposure and higher annual exposure rate. In analyses restricted to men first hired before 1960, we observed similar patterns of association but a slightly lower estimate of the ERR/100 WLM. CONCLUSIONS: This 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.

Lung Cancer and Radon: Pooled Analysis of Uranium Miners Hired in 1960 or Later.

BACKGROUND: Despite reductions in exposure for workers and the general public, radon remains a leading cause of lung cancer. Prior studies of underground miners depended heavily upon information on deaths among miners employed in the early years of mine operations when exposures were high and tended to be poorly estimated. OBJECTIVES: To strengthen the basis for radiation protection, we report on the follow-up of workers employed in the later periods of mine operations for whom we have more accurate exposure information and for whom exposures tended to be accrued at intensities that are more comparable to contemporary settings. METHODS: We conducted a pooled analysis of cohort studies of lung cancer mortality among 57,873 male uranium miners in Canada, Czech Republic, France, Germany, and the United States, who were first employed in 1960 or later (thereby excluding miners employed during the periods of highest exposure and focusing on miners who tend to have higher quality assessments of radon progeny exposures). We derived estimates of excess relative rate per 100 working level months (ERR/100 WLM) for mortality from lung cancer. RESULTS: The analysis included 1.9 million person-years of observation and 1,217 deaths due to lung cancer. The relative rate of lung cancer increased in a linear fashion with cumulative exposure to radon progeny (ERR/100 WLM=1.33; 95% CI: 0.89, 1.88). The association was modified by attained age, age at exposure, and annual exposure rate; for attained ages <55 y, the ERR/100 WLM was 8.38 (95% CI: 3.30, 18.99) among miners who were exposed at ≥35 years of age and at annual exposure rates of <0.5 working levels. This association decreased with older attained ages, younger ages at exposure, and higher exposure rates. DISCUSSION: Estimates of association between radon progeny exposure and lung cancer mortality among relatively contemporary miners are coherent with estimates used to inform current protection guidelines. https://doi.org/10.1289/EHP10669.

Innovations in applied decision theory for health and safety.

OBJECTIVES: There are established methods for occupational epidemiological cohort analysis, such as proportional hazards regression, that are well suited to aetiological research and yield parameter estimates that allow for succinct communication among academics. However, these methods are not necessarily well suited for evaluation of health impacts of policy choices and communication to decision makers. An informed decision about a policy that impacts health and safety requires a valid estimate of the policy's potential impact. METHODS: We propose methods for data summarisation that may facilitate communication with managers, workers and their advocates. We calculate measures of effect in a framework for competing events, graphically display potential impacts on cause-specific mortality under policy alternatives and contrast these results to estimates obtained using standard Poisson regression methods. Methods are illustrated using a cohort mortality study of 28 546 Ontario uranium miners hired between 1950 and 1996 and followed through 2007. RESULTS: A standard regression analysis yields a positive association between cumulative radon progeny exposure and all-cause mortality (log(RR per 100 WLM)=0.09; SE=0.02). The proposed method yields an estimate of the expected gain in life expectancy (approximately 6 months per worker) and reduction of 261 lung cancer deaths under a policy that eliminated occupational radon progeny exposure. CONCLUSIONS: The proposed method shifts attention from covariate-adjusted risk ratios or rate ratios to estimates of deaths that are avoided or delayed under a potential policy. The approach may help inform decision-making and strengthen the connection of epidemiological approaches to data analysis with developments in decision theory and systems engineering to improve health and safety.

PUMA - pooled uranium miners analysis: cohort profile.

OBJECTIVES: Epidemiological studies of underground miners have provided clear evidence that inhalation of 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 7825 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 characterisation 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.

Uncertainties associated with assessing Ontario uranium miners' exposure to radon daughters.

The Ontario uranium miners study is a large (n = 28 546) cohort with low levels of radon exposure relative to other uranium miner cohorts. Multiple methods were used over time to estimate annual occupational exposure to radon daughters including: mine-specific extrapolations by mining engineers, area sampling in limited areas of the mines combined with approximate working time and lastly, consistent exposure sampling in different locations of the mine combined with workers' time cards. Nonetheless, estimating exposures involves assumptions that lead to some uncertainty in occupational exposure characterisation arising from the assessment approach and variability within workplace, over time and by individual. An evaluation of the total uncertainty associated with radon daughter exposure estimation in Ontario miners over time has not been conducted. The objective of this study was to identify the contributing sources and assess the total uncertainty associated with estimating occupational radon daughter exposure among underground Ontario uranium miners over the course of uranium mining. The five sources of radon daughter exposure uncertainty evaluated were: natural variations in radon concentration, estimation of working time, precision of the radon measurement method, unintended errors during sampling, and record keeping and transcription of exposure data. These sources were examined separately for the period 1958 to 1967 and then 1968 onward due to changes in radon daughter concentration measurement practices between these periods. The magnitude of uncertainty associated with each of these sources over time were determined by reviewing historical literature on uranium mining in Ontario as well as through expert advice. Using the root sum square method, the total radon daughter exposure uncertainty was found to be 53 to 67% in the earlier period of uranium mining from 1958 to 1967. This decreased to 31 to 39% for the period 1968 to 1996 with natural variations of radon daughter concentrations in mines accounting for the largest percentage of uncertainty. This assessment provides an initial step in understanding the effect of exposure uncertainty on risk estimates. The impact of this uncertainty on the dose-response relationship between radon exposure and cancer risk will be assessed in future work.

Histopathologic Analysis of Lung Cancer Incidence Associated with Radon Exposure among Ontario Uranium Miners.

Although radon is a well-established contributor to lung cancer mortality among uranium miners, the effects of radon decay products on different histopathologies of lung carcinoma are not well established. Using a retrospective cohort design, this study aims to examine the risks of lung cancer by histological subtypes associated with exposure to radon decay products among the Ontario Uranium Miners cohort. Cases were stratified by histological groups, and associated risks were estimated for cumulative radon exposure after adjustment for attained age and calendar period. Between 1969 and 2005, 1274 incident cases of primary lung cancer were identified. Of these, 1256 diagnoses (99%) contained information on histology. Squamous cell carcinoma was most common (31%), followed by adenocarcinoma (20%), large cells (18%), small cell lung carcinoma (14%), and other or unspecified cell types (17%). Of the histological sub-groups, small cell lung carcinoma had the strongest association with cumulative radon exposure; compared to the reference group (<1 cumulative working level months (WLM)), the highest exposure category (>60 cumulative WLM) had a relative risk (RR) of 2.76 (95% CI: 1.67⁻4.57). Adenocarcinoma had the lowest risk and was not significantly associated with exposure to radon decay products (RR = 1.49, 95% CI: 0.96⁻2.31). An increasing, linear trend in relative risk was noted with increasing cumulative WLM across small cell, squamous cell, and large cell lung carcinomas (Ptrend < 0.05). Similarly, the excess relative risk (ERR) per WLM was highest for small cell lung carcinoma (ERR/WLM = 0.15, p < 0.01), followed by squamous cell carcinoma (ERR/WLM = 0.12, p < 0.01). Non-statistically significant excess risk was observed for adenocarcinoma (ERR/WLM = 0.004, p = 0.07). Our analysis of the Ontario Uranium Miners cohort data shows differences in the magnitude of the risks across four histological subtypes of lung carcinoma; the strongest association was noted for small cell lung carcinoma, followed by squamous cell, large cell, and lastly adenocarcinoma, which showed no significant associations with exposure to radon decay products.

Cancer incidence and mortality from exposure to radon progeny among Ontario uranium miners.

OBJECTIVES: The study objectives were to extend the follow-up of the Ontario uranium miners cohort, one of the largest cohorts of uranium miners with low cumulative exposures, to examine the relationship between radon exposure and lung cancer mortality and, for the first time incidence, and address gaps in the literature, including dose-response relationship between radon exposure and other cancer sites, and non-cancer mortality. METHODS: The cohort of mine and mill workers was created using data from Canada's National Dose Registry and the Ontario Mining Master File. The follow-up for the cohort was recently extended for mortality (1954-2007) and for the first time includes cancer incidence (1969-2005). The Poisson regression was used to estimate relative risks (RR) and excess relative risks (ERR) and their 95% CIs with levels of cumulative radon exposure. RESULTS: The cohort consisted of 28 546 male miners with a mean cumulative radon exposure of 21.0 working level months (WLM). An increased risk of lung cancer and a dose-response relationship was observed with cumulative radon exposure. Miners exposed to >100 WLM demonstrated a twofold increase in the risk of lung cancer incidence (RR=1.89, CI 1.43 to 2.50) compared with the non-exposed group, and a linear ERR of 0.64/100 WLM (CI 0.43 to 0.85), with similar results observed for mortality. No association was observed for other cancer sites (stomach, leukaemia, kidney and extrathoracic airways) or non-cancer sites (cardiovascular diseases) with increasing cumulative exposure to radon. CONCLUSIONS: These findings suggest no increased risk of cancer sites other than lung or non-cancer mortality from relatively low cumulative exposure to radon.

Health-related interventions among night shift workers: a critical review of the literature.

OBJECTIVES: Associations between shift work and chronic disease have been observed, but relatively little is known about how to mitigate these adverse health effects. This critical review aimed to (i) synthesize interventions that have been implemented among shift workers to reduce the chronic health effects of shift work and (ii) provide an overall evaluation of study quality. METHODS: MeSH terms and keywords were created and used to conduct a rigorous search of MEDLINE, CINAHL, and EMBASE for studies published on or before 13 August 2012. Study quality was assessed using a checklist adapted from Downs & Black. RESULTS: Of the 5053 articles retrieved, 44 met the inclusion and exclusion criteria. Over 2354 male and female rotating and permanent night shift workers were included, mostly from the manufacturing, healthcare, and public safety industries. Studies were grouped into four intervention types: (i) shift schedule; (ii) controlled light exposure; (iii) behavioral; and, (iv) pharmacological. Results generally support the benefits of fast-forward rotating shifts; simultaneous use of timed bright light and light-blocking glasses; and physical activity, healthy diet, and health promotion. Mixed results were observed for hypnotics. Study quality varied and numerous deficiencies were identified. CONCLUSIONS: Except for hypnotics, several types of interventions reviewed had positive overall effects on chronic disease outcomes. There was substantial heterogeneity among studies with respect to study sample, interventions, and outcomes. There is a need for further high-quality, workplace-based prevention research conducted among shift workers.

Fertilizer use and self-reported respiratory and dermal symptoms among tree planters.

In British Columbia, some tree planting operations require workers to fertilize planted seedlings with polymer-coated nitrogen, phosphorus, and potassium (NPK) fertilizers. This study examined respiratory and dermal health associated with fertilizer exposure among tree planters. We interviewed 223 tree planters using an adapted version of the American Thoracic Society questionnaire supplemented with questions on dermal health. Subjects were grouped by categories of increasing duration of exposure, with workers who had not worked with fertilizer as a reference group. The relationship between exposure and reported work-related symptoms was analyzed using logistic regression, adjusting for age, cumulative tobacco cigarettes smoked, marijuana smoking status, sex, and exposure to abrasive spruce needles. An elevated odds ratio was seen for work-related cough, phlegm, nasal symptoms, nosebleed, and skin rash in the highest exposure group (>37 days of fertilizer use in the past 2 years) but was significant only for phlegm (odds ratio = 3.59, 95% confidence interval = 1.10-11.70). Trends of increasing odds ratios with increasing exposure were seen for cough, phlegm, nasal symptoms, and skin rash. The results suggest a weak association between respiratory and dermal irritation and work with fertilizer. Results highlight the need for further exposure monitoring within the tree planting industry, and larger studies to investigate the relationship between work with fertilizer and respiratory and dermal health symptoms. [Supplementary materials are available for this article. Go to the publisher's online edition of the Journal of Occupational and Environmental Hygiene for the following free supplemental resource: a PDF file containing a respiratory and dermal health questionnaire.].