Neurotoxic effects of home radon exposure on oscillatory dynamics serving attentional orienting in children and adolescents.

Radon is a naturally occurring gas that contributes significantly to radiation in the environment and is the second leading cause of lung cancer globally. Previous studies have shown that other environmental toxins have deleterious effects on brain development, though radon has not been studied as thoroughly in this context. This study examined the impact of home radon exposure on the neural oscillatory activity serving attention reorientation in youths. Fifty-six participants (ages 6-14 years) completed a classic Posner cuing task during magnetoencephalography (MEG), and home radon levels were measured for each participant. Time-frequency spectrograms indicated stronger theta (3-7 Hz, 300-800 ms), alpha (9-13 Hz, 400-900 ms), and beta responses (14-24 Hz, 400-900 ms) during the task relative to baseline. Source reconstruction of each significant oscillatory response was performed, and validity maps were computed by subtracting the task conditions (invalidly cued - validly cued). These validity maps were examined for associations with radon exposure, age, and their interaction in a linear regression design. Children with greater radon exposure showed aberrant oscillatory activity across distributed regions critical for attentional processing and attention reorientation (e.g., dorsolateral prefrontal cortex, and anterior cingulate cortex). Generally, youths with greater radon exposure exhibited a reverse neural validity effect in almost all regions and showed greater overall power relative to peers with lesser radon exposure. We also detected an interactive effect between radon exposure and age where youths with greater radon exposure exhibited divergent developmental trajectories in neural substrates implicated in attentional processing (e.g., bilateral prefrontal cortices, superior temporal gyri, and inferior parietal lobules). These data suggest aberrant, but potentially compensatory neural processing as a function of increasing home radon exposure in areas critical for attention and higher order cognition.

Radon Exposure and Incident Stroke Risk in the Women's Health Initiative.

BACKGROUND AND OBJECTIVES: Little is known about the role of radon in the epidemiology of stroke among women. We therefore examined the association between home radon exposure and risk of stroke among middle-aged and older women in the United States. METHODS: We conducted a prospective cohort study of postmenopausal women aged 50-79 years at baseline (1993-1998) in the Women's Health Initiative. We measured exposures as 2-day, indoor, lowest living-level average radon concentrations in picocuries per liter (pCi/L) as estimated in 1993 by the US Geological Survey and reviewed by the Association of American State Geologists under the Indoor Radon Abatement Act. We used Cox proportional hazards models to estimate risk of incident, neurologist-adjudicated stroke during follow-up through 2020 as a hazard ratio and 95% CI, adjusting for study design and participant demographic, social, behavioral, and clinical characteristics. RESULTS: Among 158,910 women without stroke at baseline (mean age 63.2 years; 83% white), 6,979 incident strokes were identified over follow-up (mean 13.4 years). Incidence rates were 333, 343, and 349 strokes per 100,000 woman-years at radon concentrations of <2, 2-4, and >4 pCi/L, respectively. Compared with women living at concentrations <2 pCi/L, those at 2-4 and >4 pCi/L had higher covariate-adjusted risks of incident stroke: hazard ratio (95% CI) 1.06 (0.99-1.13) and 1.14 (1.05-1.22). Using nonlinear spline functions to model radon, stroke risk was significantly elevated at concentrations ranging from 2 to 4 pCi/L (p = 0.0004), that is, below the United States Environmental Protection Agency Radon Action Level for mitigation (4 pCi/L). Associations were slightly stronger for ischemic (especially cardioembolic, small vessel occlusive, and large artery atherosclerotic) than hemorrhagic stroke, but otherwise robust in sensitivity analyses. DISCUSSION: Radon exposure is associated with moderately increased stroke risk among middle-aged and older women in the United States, suggesting that promulgation of a lower Radon Action Level may help reduce the domestic impact of cerebrovascular disease on public health.

A Study on Geographic Correlation between Indoor Radon Exposure and Leukemia Incidence in Canada.

ABSTRACT: In Canada, leukemia is diagnosed at a rate of 15 cases per 100,000 persons and accounts for about 3% of all new primary cancers. In this study, geographical correlation between residential radon exposure and leukemia incidence was investigated at a provincial level with more accurate long-term radon measurement data in 21,330 homes and 10-y (2000-2009) age standardized incidence rates per 100,000 population for various subtypes of leukemia. The analyses showed that the incidence rate of non-Hodgkin lymphoma is statistically significantly correlated with average indoor radon (222Rn) concentration for Canadian females (p = 0.01210) but not for males. At a provincial level, the association between average indoor radon level and chronic lymphocytic leukemia incidence rate is statistically significant (p = 0.0167), and the correlation is somewhat stronger for females (p = 0.0043). No correlation was found between indoor radon exposure and any other subtypes of leukemia evaluated in this study.

Radon exposure risks among residents proximal to gold mine tailings in Gauteng Province, South Africa: a cross-sectional preliminary study protocol.

Gold mine tailings, a legacy of the mining industry, harbors significant amount of radon gas, a classified human carcinogen. Radon exposure, especially near tailings, is a significant public health threat, potentially leading to increased risk of lung cancer, leukemia, and chronic obstructive pulmonary disease (COPD). These health problems are often associated with lower survival rates and significant financial burdens. This ongoing research aim to evaluating the relationship between indoor radon exposure and lung cancer, leukemia, and COPD risks among residents proximal to gold mine tailings in Gauteng Province, South Africa. This cross-sectional preliminary study focus on two distinct groups: Riverlea (exposed group, <2 km to Gold mine tailings) and Orlando East (unexposed group, >2 km to Gold mine tailings). Indoor radon levels is measured using AlphaE monitors, while health risks (lung cancer, leukemia, and COPD) linked to exposure are evaluated through interview-administered questionnaire and secondary data from Gauteng Health Department. Of the 476 residents randomly selected for this study, 300 have already participated, with balanced representation from both the exposed and unexposed groups. The study will compare indoor radon levels and health outcomes between the two groups. This study's results could aid in creating targeted interventions and policies to mitigate indoor radon exposure risks and safeguard vulnerable communities from this significant public health hazard.

Rural communities experience higher radon exposure versus urban areas, potentially due to drilled groundwater well annuli acting as unintended radon gas migration conduits.

Repetitive, long-term inhalation of radioactive radon gas is one of the leading causes of lung cancer, with exposure differences being a function of geographic location, built environment, personal demographics, activity patterns, and decision-making. Here, we examine radon exposure disparities across the urban-to-rural landscape, based on 42,051 Canadian residential properties in 2034 distinct communities. People living in rural, lower population density communities experience as much as 31.2% greater average residential radon levels relative to urban equivalents, equating to an additional 26.7 Bq/m3 excess in geometric mean indoor air radon, and an additional 1 mSv/year in excess alpha radiation exposure dose rate to the lungs for occupants. Pairwise and multivariate analyses indicate that community-based radon exposure disparities are, in part, explained by increased prevalence of larger floorplan bungalows in rural areas, but that a majority of the effect is attributed to proximity to, but not water use from, drilled groundwater wells. We propose that unintended radon gas migration in the annulus of drilled groundwater wells provides radon migration pathways from the deeper subsurface into near-surface materials. Our findings highlight a previously under-appreciated determinant of radon-induced lung cancer risk, and support a need for targeted radon testing and reduction in rural communities.

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.

Radon Exposure, Clonal Hematopoiesis, and Stroke Susceptibility in the Women's Health Initiative.

BACKGROUND AND OBJECTIVES: Studies suggest that clonal hematopoiesis of indeterminate potential (CHIP) may increase risk of hematologic malignancy and cardiovascular disease, including stroke. However, few studies have investigated plausible environmental risk factors for CHIP such as radon, despite the climate-related increases in and documented infrequency of testing for this common indoor air pollutant.The purpose of this study was to estimate the risk of CHIP related to radon, an established environmental mutagen. METHODS: We linked geocoded addresses of 10,799 Women's Health Initiative Trans-Omics for Precision Medicine (WHI TOPMed) participants to US Environmental Protection Agency-predicted, county-level, indoor average screening radon concentrations, categorized as follows: Zone 1 (>4 pCi/L), Zone 2 (2-4 pCi/L), and Zone 3 (<2 pCi/L). We defined CHIP as the presence of one or more leukemogenic driver mutations with variant allele frequency >0.02. We identified prevalent and incident ischemic and hemorrhagic strokes; subtyped ischemic stroke using Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria; and then estimated radon-related risk of CHIP as an odds ratio (OR) and 95% CI using multivariable-adjusted, design-weighted logistic regression stratified by age, race/ethnicity, smoking status, and stroke type/subtype. RESULTS: The percentages of participants with CHIP in Zones 1, 2, and 3 were 9.0%, 8.4%, and 7.7%, respectively (ptrend = 0.06). Among participants with ischemic stroke, Zones 2 and 1 were associated with higher estimated risks of CHIP relative to Zone 3: 1.39 (1.15-1.68) and 1.46 (1.15-1.87), but not among participants with hemorrhagic stroke: 0.98 (0.68-1.40) and 1.03 (0.70-1.52), or without stroke: 1.04 (0.74-1.46) and 0.95 (0.63-1.42), respectively (pinteraction = 0.03). Corresponding estimates were particularly high among TOAST-subtyped cardioembolism: 1.78 (1.30-2.47) and 1.88 (1.31-2.72), or other ischemic etiologies: 1.37 (1.06-1.78) and 1.50 (1.11-2.04), but not small vessel occlusion: 1.05 (0.74-1.49) and 1.00 (0.68-1.47), respectively (pinteraction = 0.10). Observed patterns of association among strata were insensitive to attrition weighting, ancestry adjustment, prevalent stroke exclusion, separate analysis of DNMT3A driver mutations, and substitution with 3 alternative estimates of radon exposure. DISCUSSION: The robust elevation of radon-related risk of CHIP among postmenopausal women who develop incident cardioembolic stroke is consistent with a potential role of somatic genomic mutation in this societally burdensome form of cerebrovascular disease, although the mechanism has yet to be confirmed.

The role of sex and gender in the diagnosis and treatment of lung cancer: the 6th ICAPEM Annual Symposium.

The incidence and mortality of lung cancer in women are rising, with both increasing by 124% between 2003 and 2019. The main risk factor for lung cancer is tobacco use, but indoor radon gas exposure is one of the leading causes in nonsmokers. The most recent evidence demonstrates that multiple factors can make women more susceptible to harm from these risk factors or carcinogens. For this consensus statement, the Association for Lung Cancer Research in Women (ICAPEM) invited a group of lung cancer experts to perform a detailed gender-based analysis of lung cancer. Clinically, female patients have different lung cancer profiles, and most actionable driver alterations are more prevalent in women, particularly in never-smokers. Additionally, the impact of certain therapies seems to be different. In the future, it will be necessary to carry out specific studies to improve the understanding of the role of certain biomarkers and gender in the prognosis and evolution of lung cancer.

Paracelsian 'Bergsucht' - lung cancer or radiation-induced fibrosis?

PURPOSE: Assessment of absorbed doses on organs and tissues of miners during radon exposure in the Schneeberg mines in the sixteenth century and calculation of the probability of occurrence of radiation-induced lung cancer and lung fibrosis, considering the life expectancy characteristic and the absence of smoking. MATERIALS AND METHODS: The expected radon concentration at the Schneeberg mines has been estimated using published data. Modeling of the accumulation of radon in the working tunnels of mine workings was carried out using the RESRAD-Build 4.0, based on the radium concentration in soil and geometric parameters of the mining tunnel from the engravings in Agricola's book. The dynamics of radionuclides in the human body were performed using the WinAct software in accordance with data from ICRP Publications 130 and 137. The values of absorbed doses on the tissues of the respiratory tract were obtained using the IDAC 2.1 program. Several models based on the epidemiology of uranium miners have been used to calculate radiation risks from radon exposure. The probability of male survival at birth and the age-specific frequency of spontaneous lung cancer not associated with radiation for miners of the sixteenth century (nonsmoking men aged 20-40 years) were estimated to properly calculate the radiation risks. RESULTS: The expected radon concentration in the Schneeberg mines was assessed in the range of 75-100 kBq m-3. The average value of the equilibrium factor was estimated as 0.49 ± 0.03. The annual exposure of miners to radon decay products was assessed as 125-165 WLM year-1. The annual values of absorbed doses to different sections of the respiratory tract were calculated, the maximum absorbed doses of α-radiation are formed on the bronchial and bronchiolar regions of the lungs (2.23 Gy year-1). The deterministic effects as radiation fibrosis of the lungs with 10 years of experience in the mines of Schneeberg have a probability of occurrence from 60 to 100%. All the models used for radiation risk assessments showed that the lifetime risk of developing lung cancer for nonsmoking Schneeberg miners is many times lower than the risk of developing deterministic radiation effects. In contrast, for the smoking cohort of miners in the nineteenth century lung cancer become the dominant cause of death. CONCLUSIONS: The deterministic radiation effects of Schneeberg miners in sixteenth century, exposed to extremely high levels of radon, such as radiation pneumosclerosis or pulmonary fibrosis, are more likely than the development of radiation-induced lung cancer.

Assessment of radiological risk associated with thoron gas at primary schools in Al-Najaf city, Iraq.

Children spend considerable time at home and school, so school is likely to be a second source of natural radionuclide exposure after home. This study evaluates the radiological risk associated with thoron gas in the air within the building of one hundred primary schools in Al-Najaf City, Iraq, using a CR-39 detector. The results of the average value of thoron concentration detector, the annual effective dose (AED), Excessive Lifetime Cancer Risk (ELCR) × 10-3, and Lung Cancer Case (LCC) × 10-9 measured in the building of the schools were 7.47 ± 2.85 Bq/m3, 0.03 ± 0.01 mSv/y, 0.11 ± 0.04, and 0.54 ± 0.20, respectively. All the results of indoor thoron were below the global average limit. The results of the radiological survey due to thoron concentrations for studied primary schools suggest that the radionuclides and their radiological hazard indexes in all studied schools in AL Najaf city, Iraq, do not impose a health hazard.

Radon activity concentration RnCA and workers lung cancer risks in SENA coal mines, Colombia.

The risk of lung cancer or pneumoconiosis mortality, increases with radioactive radon gas exposures. This article report health risk for underground workers exposed to radioactive gas and radon daughters carried by airborne dust at the coal mining in the Central Mountainous Region of Colombia. A set of 33 measurement points located in that mine galleries were selected to monitor radon gas concentration activity, by passive LR-115 detectors, during two months. Resulting values provided radon concentrations, absorbed dose, environmental equivalent dose and the effective dose; miners increased risk of contracting lung cancer is included. It is concluded that the mine ventilation system satisfies the conditions required by the current radiological protection of the miners. Our study point out that Colombia can effectively address the potential risks associated with radon exposure and ensure a safer living environment for its citizens.

Radon exposure: a major cause of lung cancer in nonsmokers.

Exposure to radon can impact human health. This is a nonsystematic review of articles written in English, Spanish, French, or Portuguese published in the last decade (2013-2023), using databases such as PubMed, Google Scholar, EMBASE, and SciELO. Search terms selected were radon, human health, respiratory diseases, children, and adults. After analyzing the titles and abstracts, the researchers initially identified 47 studies, which were subsequently reduced to 40 after excluding reviews, dissertations, theses, and case-control studies. The studies have shown that enclosed environments such as residences and workplaces have higher levels of radon than those outdoors. Moreover, radon is one of the leading causes of lung cancer, especially in nonsmokers. An association between exposure to radon and development of other lung diseases, such as asthma and COPD, was also observed. It is crucial to increase public awareness and implement governmental control measures to reduce radon exposure. It is essential to quantify radon levels in all types of buildings and train professionals to conduct such measurements according to proven efficacy standards. Health care professionals should also be informed about this threat and receive adequate training to deal with the effects of radon on human health.

Behaviourally-informed household communications increase uptake of radon tests in a randomised controlled trial.

Exposure to radon gas is a leading cause of lung cancer. Testing homes for the gas is straightforward, yet most people do not undertake tests even when offered freely. We report a pre-registered randomised controlled trial of communications to encourage test uptake. Households (N = 3500) in areas at high risk of radon exposure were randomly assigned to receive (i) a the control letter from the national Environmental Protection Agency; (ii) a behaviourally-informed version of the control letter that incorporated multiple nudges, including reciprocity messages and numeric frequencies of risk; (iii) this same behaviourally-informed letter in a re-designed envelope; (iv) the behaviourally-informed letter in the re-designed enveloped with a radon risk map of the household's county. The behaviourally-informed letter led to a large increase in test uptake, from 22% in the control condition to 33% (a 50% increase). There was no additional benefit of the re-designed envelope, which generated uptake of 30%. Including the map led some households to respond faster, but the overall uptake (26%) was weaker. The results have implications for public health communications with households and show the potential for techniques from behavioural science to help mitigate environmental risks.

Smoking Modifies the Association Between Radon Exposure and Incident Ischemic Stroke: The REGARDS Study.

BACKGROUND: Exposure to radon has been linked to lung cancer and other lung diseases. Although biologically plausible, research of residential radon exposure in relation to stroke risk is scarce. METHODS: Study participants were from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort (n=30 239), which consisted of male and female non-Hispanic Black and White adults aged 45 and older. After excluding participants with baseline stroke and transient ischemic attack, and missing information on exposure and outcome of interest, the final sample size was 26 950. The primary outcome was time to the first ischemic stroke through September 30, 2020. County-level radon measures from Lawrence Berkeley National Laboratory were linked to each participant based on their geocoded residential history. We used Cox proportional hazards regression models with a time-dependent exposure to estimate hazard ratios and 95% CIs for the association. RESULTS: After controlling for potential confounding factors including demographic, lifestyle, clinical variables, and PM2.5, radon exposure was significantly associated with incident ischemic stroke among never-smokers (hazard ratio, 1.39 [95% CI, 1.01-1.90]) but not ever-smokers. The results were generally consistent in the sensitivity analysis when using radon measures from state/Environmental Protection Agency residential radon survey. CONCLUSIONS: Findings from this study suggest that the association between residential radon exposure and incidence of ischemic stroke varies by smoking status and may be prominent in never-smokers. Further studies incorporating indoor-radon measures are needed to confirm these findings.

Preliminary study of chromosome aberrations using Giemsa, two-colour fish, and micronucleus assays in lymphocytes of individuals living in elevated radon concentration areas.

The frequencies of unstable and stable chromosome aberrations and micronuclei were examined in peripheral blood samples from 10 individuals living in elevated radon concentration areas (Takandeang Village, Mamuju, Indonesia). Blood samples from 10 people living in Topoyo Village were used as a control group. For unstable chromosome aberration analysis, a dicentric chromosome assay was conducted using conventional Giemsa staining. Chromosomal painting of chromosomes 1 and 4 using the fluorescence in situ hybridisation technique was also applied to four subjects to assess the stable chromosome aberration. Our study showed no significant increases across all groups in dicentric and other unstable chromosome aberrations, such as rings and acentric fragments. Translocations were found in one person from Takandeang Village and two Topoyo Village inhabitants. The translocations found in the subjects from Takandeang Village were due more to aging factors than to radon exposure. The number of micronuclei per 1000 binucleus cells in Takandeang Village inhabitants was not significantly different than that in the control group (p = 0.943). A more comprehensive analysis should be conducted in a subsequent study by increasing the number of study donors and the number of metaphases to be analysed in both dicentric chromosome assay and fluorescence in situ hybridisation assays. Such research could provide valid information on the cytogenetic effects of elevated indoor radon exposure.

Indoor radon exposure and living conditions in patients with advanced lung cancer in Lublin region, Poland.

OBJECTIVE: Radon (Rn-222) is a noble gas formed in the uranium path (U-238) as a decay product of radium (Ra-226). It is estimated to cause between 3% to 14% of all lung cancers, depending on the national average radon level and smoking prevalence. Radon molecules emit alpha radiation, which is characterized by low permeability through tissues, but due to its remarkably high energy, it has a high potential for DNA damage. The aim of our research was to assess the radon concentration inside the houses of patients with advanced lung cancer and to analyze their socio-economics status. PATIENTS AND METHODS: The measurements of radon concentration were performed in 102 patients with stage 3B or higher lung cancer in the region of Lublin, Poland. One month of radon exposure measurement was performed with alpha-track detectors. In addition, patients filled in a detailed survey about factors that might influence the concentration of radon inside their houses. RESULTS: The average concentration of radon during the exposure of the detector in the residential premises of the respondents was at the level of 69.0 Bq/m3 [37.0-117.0]. A few significant correlations were discovered, e.g., higher levels of radon in countryside houses or in houses equipped with air conditioning. CONCLUSIONS: As radon exposure is a modifiable risk factor for lung cancer, it is extremely important to find factors that may reduce its concentration in dwelling places. Since our research was performed in houses of people with lung cancer, taking corrective actions based on our findings could prevent new lung cancer incidence in patients' flatmates.

An overview on the relationship between residential radon and lung cancer: what we know and future research.

We aim to provide an overview of the research available on indoor radon and lung cancer, with a special focus on Spanish investigations. Early studies on underground miners established the link between radon and lung cancer, which was later confirmed for the general population by residential case-control studies. Spain contributed with extensive evidence, including 5 multicentric, hospital-based, case-control studies in the last 30 years, exploring diverse aspects, such as radon's effect on never-smokers, molecular pathways linking radon exposure to lung cancer risk, survival rates, mortality burden, and occupational exposure. There is a well-established causal association between radon with lung cancer. Despite pioneering research performed in our country by the Galician Radon Laboratory, particularly on driver genes, the evidence on the potential molecular pathways which makes radon a carcinogen is sparse. Also, relevant questions on the potential association of radon exposure with the induction of other diseases are still pending.

Influence of the natural radon radiation on the spread of the COVID 19 pandemic.

The statistics of COVID-19 accumulated in Ukraine show areas with a significantly lower incidence of diseases. The purpose of the study was to identify factors that could influence the pattern of the pandemic in a particular area. Within the study it was assumed that the level of health care is approximately the same throughout the country. Population density was considered the main factor influencing the dynamics of the spread of infection. To reduce the impact of changes in population density across regions, it was normalized by the average population density in the country. The normalization of statistics for the country resulted in a model in the form of a linear relationship between the normalized values of the number of COVID-19 cases in the region and the size of the region. Subsequent analysis of the graphical data made it possible to identify four regions with the lowest incidence of COVID-19. The geographical proximity of these regions Dnipro, Kherson, Vinnytsia and Kirovograd, indicates the presence of a common factor for them, not typical for the rest of Ukraine. Such a factor may be the location of 83% of Ukraine's uranium deposits in the territories around Kirovohrad. Radon is one of the decay products of uranium, so the population of these areas may experience increased exposure to radon. This noble gas has more than a century of medical use, in particular for pulmonary diseases, although there is still no consensus about its effectiveness and side effects. Considering that COVID-19 was often complicated by pulmonary diseases, it can be assumed that the geological specificity of these four regions of Ukraine had an impact on the course of the COVID-19 pandemic in their territories. The study findings are important in terms of further COVID-19 research and prevention strategies.

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.