Radon-related Lung Cancer Research Articles

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.

Quantitative evaluation of radon, tobacco use and lung cancer association in an occupational cohort with 27 follow-up years

BackgroundOccupational radon cohorts provide important information about exposure at residential level, which are difficult to observe prospectively. However, evidence about radon-related lung cancer risks from initial exposure in childhood or interaction between radon and smoking is still limited. MethodsA total of 6017 tin miners with at least 10 years of underground radon exposure were enrolled beginning in 1992 and followed for up to 27 years. Lung cancer risks were estimated by modeling total and intensity of radon exposure. ResultsA total of 933 lung cancer cases occurred in this cohort over 89,092 person-years of follow up. Excess relative risk increased by 0.96% per cumulative working level month (WLM). A unique aspect of this population was the early age at first radon exposure for workers. Results showed that lung cancer risk from initial radon exposure in childhood (<13 years old) was greater than risk when first exposure occurred at later ages (13–17, 18–24, and ≥ 25 years old). Moreover, risk declined with years since last exposure and attained age, but increased with age at last exposure. Importantly, these patterns were stable after adjustment for tobacco use or arsenic exposure. For joint effects of radon and other agents, our results support sub-multiplicative as the most likely model for interaction between radon and tobacco use or arsenic exposure. ConclusionThis study highlights the possible importance of radon exposure in childhood in cancer etiology and suggests another potential strategy to mitigate the global lung cancer burden.

Understanding geographic variations of indoor radon potential for comprehensive cancer control planning.

Lung cancer is the leading cause of U.S. cancer deaths and radon is the second leading risk factor for lung cancer. By better understanding geologic variations of radon production in states, comprehensive cancer control efforts could be improved. The study purpose was to assess states with the greatest potential for elevated radon and the likelihood of radon-related actions in National Comprehensive Cancer Control Program (NCCCP) awardee cancer plans. Two state-level variables were derived to approximate potential for elevated radon using the Environmental Protection Agency county map and the 2015 U.S. Census. The association between radon potential and inclusion of radon activity within cancer plans was evaluated using logistic regression. Fifty-one percent of cancer plans recognized an association between radon and cancer risk, and included measurable radon activities. Most states with high radon potential included radon activity in cancer plans. Both measures of radon potential were significantly associated with NCCCP cancer plans including radon activity. Geospatial analyses help to prioritize radon-related lung cancer activities. In areas with high potential for radon exposure, increasing knowledge about potential for radon exposure may result in increased radon testing, mitigation, or other radon reducing strategies, and ultimately reduction of lung cancer deaths.

Estimation of residential radon exposure and definition of Radon Priority Areas based on expected lung cancer incidence

Radon is a naturally occurring gas, classified as a Class 1 human carcinogen, being the second most significant cause of lung cancer after tobacco smoking. A robust spatial definition of radon distribution in the built environment is therefore essential for understanding the relationship between radon exposure and its adverse health effects on the general population. Using Ireland as a case study, we present a methodology to estimate an average indoor radon concentration and calculate the expected radon-related lung cancer incidence. We use this approach to define Radon Priority Areas at the administrative level of Electoral Divisions (EDs).Geostatistical methods were applied to a data set of almost 32,000 indoor radon measurements, sampled in Ireland between 1992 and 2013. Average indoor radon concentrations by ED range from 21 to 338 Bq m−3, corresponding to an effective dose ranging from 0.8 to 13.3 mSv y−1 respectively. Radon-related lung cancer incidence by ED was calculated using a dose-effect model giving between 15 and 239 cases per million people per year, depending on the ED. Based on these calculations, together with the population density, we estimate that of the approximately 2,300 lung cancer cases currently diagnosed in Ireland annually, about 280 may be directly linked to radon exposure. This figure does not account for the synergistic effect of radon exposure with other factors (e.g. tobacco smoking), so likely represents a minimum estimate. Our approach spatially defines areas with the expected highest incidence of radon-related lung cancer, even though indoor radon concentrations for these areas may be moderate or low. We therefore recommend that both indoor radon concentration and population density by small area are considered when establishing national radon action plans.

Factors Modifying the Radon-Related Lung Cancer Risk at Low Exposures and Exposure Rates among German Uranium Miners.

It is still not fully understood whether and how factors such as time, age and smoking modify the relationship between lung cancer and radon at low exposures and exposure rates. Improved knowledge is necessary for the dose conversion of radon in working level month (WLM) into effective dose, as currently discussed by the International Commission on Radiological Protection (ICRP). An update of the German uranium miner cohort study (n = 58,974 men) with a 10-year extension of mortality follow-up (1946-2013) was used to further examine this issue. Internal Poisson regression was applied to estimate the excess relative risk (ERR) for lung cancer mortality per unit of cumulative radon exposure in WLM with exponential time-related effect modifiers. In the full cohort restricted to <100 WLM the estimated overall ERR/WLM was 0.006 [95% confidence interval (CI): 0.003; 0.010] based on 1,254 lung cancer deaths and 1,620,190 person-years at risk. Both age at and time since exposure turned out to be important modifiers of the ERR/WLM and were included in the final model. Here, the ERR/WLM centered on age at exposure of 30 years, and 20 years since exposure was 0.016 (95% CI: 0.008; 0.028). This value decreased statistically significantly by approximately 40% and 60% for each 10-year increase in age at exposure and time since exposure, respectively. The joint effect of smoking and radon exposure was investigated in the sub-cohort of miners hired in 1960 or later, which includes data on smoking status. The centered ERR/WLM was slightly higher for non/light smokers compared to moderate/heavy smokers (0.022 versus 0.013). The current findings provide evidence for an increased lung cancer risk at low radon exposures or exposure rates that is modified by age and time. The observed risk is lower, but statistically compatible to those of other miner studies at low exposures or exposure rates. These findings reject an additive- and support a sub- to (supra-) multiplicative interaction between smoking and radon.

Lung cancer risk from radon in Ontario, Canada: how many lung cancers can we prevent?

PurposeTo calculate the burden of lung cancer illness due to radon for all thirty-six health units in Ontario and determine the number of radon-attributable lung cancer deaths that could be prevented. MethodsWe calculated the population attributable risk percent, excess life-time risk ratio, life-years lost, the number of lung cancer deaths due to radon, and the number of deaths that could be prevented if all homes above various cut-points were effectively reduced to background levels.ResultsIt is estimated that 13.6 % (95 % CI 11.0, 16.7) of lung cancer deaths in Ontario are attributable to radon, corresponding to 847 (95 % CI 686, 1,039) lung cancer deaths each year, approximately 84 % of these in ever-smokers. If all homes above 200 Bq/m3, the current Canadian guideline, were remediated to background levels, it is estimated that 91 lung cancer deaths could be prevented each year, 233 if remediation was performed at 100 Bq/m3. There was important variation across health units.ConclusionsRadon is an important contributor to lung cancer deaths in Ontario. A large portion of radon-attributable lung cancer deaths are from exposures below the current Canadian guideline, suggesting interventions that install effective radon-preventive measures into buildings at build may be a good alternative population prevention strategy to testing and remediation. For some health units, testing and remediation may also prevent a portion of radon-related lung cancer deaths. Regional attributable risk estimates can help with local public health resource allocation and decision making.

The impact of declining smoking on radon-related lung cancer in the United States.

We examined the effect of current patterns of smoking rates on future radon-related lung cancer. We combined the model developed by the National Academy of Science's Committee on Health Risks of Exposure to Radon (the BEIR VI committee) for radon risk assessment with a forecasting model of US adult smoking prevalence to estimate proportional decline in radon-related deaths during the present century with and without mitigation of high-radon houses. By 2025, the reduction in radon mortality from smoking reduction (15 percentage points) will surpass the maximum expected reduction from remediation (12 percentage points). Although still a genuine source of public health concern, radon-induced lung cancer is likely to decline substantially, driven by reductions in smoking rates. Smoking decline will reduce radon deaths more that remediation of high-radon houses, a fact that policymakers should consider as they contemplate the future of cancer control.

Differences in baseline lung cancer mortality between the German uranium miners cohort and the population of the former German Democratic Republic (1960–2003)

A previous analysis of the radon-related lung cancer mortality risk, in the German uranium miners cohort, using Poisson modeling techniques, noted internal (spontaneous) rates that were higher on average than the external rates by 16.5% (95% CI: 9%; 24%). The main purpose of the present paper is to investigate the nature of, and possible reasons for, this difference by comparing patterns in spontaneous lung cancer mortality rates in a cohort of male miners involved in uranium extraction at the former Wismut mining company in East Germany with national male rates from the former German Democratic Republic. The analysis is based on miner data for 3,001 lung cancer deaths, 1.76 million person-years for the period 1960-2003, and national rates covering the same calendar-year range. Simple "age-period-cohort" graphical analyses were applied to assess the main qualitative differences between the national and cohort baseline lung cancer rates. Some differences were found to occur mainly at higher attained ages above 70 years. Although many occupational risk factors may have contributed to these observed age differences, only the effects of smoking have been assessed here by applying the Peto-Lopez indirect method for calculating smoking attributability. It is inferred that the observed age differences could be due to the greater prevalence of smoking and more mature smoking epidemic in the Wismut cohort compared to the general population of the former German Democratic Republic. In view of these observed differences between external population-based rates and internal (spontaneous) cohort baseline lung cancer rates, it is strongly recommended to apply only the internal rates in future analyses of uranium miner cohorts.

Estimates of Costs for Housing-Related Interventions to Prevent Specific Illnesses and Deaths

Public health is embracing economic analyses in an effort to use limited resources in the most efficient manner. However, users of economic analyses in the public health arena should recognize the inherent strengths and weaknesses of different types of analysis, as well as understand how the inclusion or omission of certain costs or benefits might influence study results. For example, asthma is a chronic condition that can result in health care costs that accrue well beyond the duration of a housing intervention. Thus, an economic analysis that omits long-term health care costs can underestimate the total economic benefit of the housing intervention. This article contains reviews of economic articles on housing interventions published in PubMed, examines salient differences between studies, and discusses pertinent gaps in the literature. In addition, this article attempts to provide an overview of key economic evaluation methods in relation to housing interventions to a target audience of local and state public health practitioners. Specific housing-related health issues discussed include asthma, lead, and carbon monoxide poisoning and radon-related lung cancer.

ACCOUNTING FOR SMOKING IN THE RADON-RELATED LUNG CANCER RISK AMONG GERMAN URANIUM MINERS: RESULTS OF A NESTED CASE-CONTROL STUDY

The possible confounding effect of smoking on radon-associated risk for lung cancer mortality was investigated in a case-control study nested in the cohort of German uranium miners. The study included 704 miners who died of lung cancer and 1,398 controls matched individually for birth year and attained age. Smoking status was reconstructed from questionnaires and records from the mining company's health archives for 421 cases and 620 controls. Data on radon exposure were taken from a job-exposure matrix. Smoking adjusted odds ratios for lung cancer in relation to cumulative radon exposure have been calculated with conditional logistic regression. The increase in risk per Working Level Month (WLM) was assessed with a linear excess relative risk (ERR) model taking smoking into account as a multiplicative factor. In addition, the potential impact of temporal factors on the ERR per WLM was examined. Lung cancer mortality risk increased with increasing radon exposure, yielding a crude ERR per WLM of 0.25% (95% CI: 0.13-0.46%). Adjustment for smoking led only to marginal changes of the radon-associated lung cancer risks. The adjusted ERR per WLM was very similar (0.23%, 95%-CI: 0.11-0.46%) to the crude risk and to the risk found in the Wismut cohort study. This stability of the radon-related lung cancer risks with and without adjustment for smoking suggests that smoking does not act as a major confounder in this study and presumably also not in the cohort study.

A Simulation Study of Radon and Thoron Discrimination Problem in Case-Control Studies

In most countries, radon is the dominant contributor among natural radiation sources to the radiation exposure dose of the general population. Numerous case-control studies of residential radon and lung cancer have been conducted using passive radon (Rn-222) detectors. These studies showed that radon may increase lung cancer risk, but most of them did not show a significant risk. Recently it was shown that the readings of passive radon detectors that do not employ thoron (Rn-220) discrimination techniques are affected by thoron. Therefore, we conducted a simulation study to evaluate the possible effect of thoron interference on the estimation of radon-related lung cancer risk. Various assumptions were made based on the number of cases, matching ratio, baseline risk, true radon-related risk, distribution of radon and thoron concentrations, correlation between radon and thoron, and radon detectors. The results suggested that in certain circumstances thoron interference in radon measurements resulted in an approximately 90% downward bias. In addition, the magnitude of the bias increased as the geometric mean and geometric standard error of radon concentration decreased and those of thoron increased. In order to resolve this problem, it is necessary to use passive radon detectors with thoron discrimination techniques in epidemiological studies.

Assessment of the Effectiveness of Radon Screening Programs in Reducing Lung Cancer Mortality

The present study was aimed at assessing the health consequences of the presence of radon in Quebec homes and the possible impact of various screening programs on lung cancer mortality. Lung cancer risk due to this radioactive gas was estimated according to the cancer risk model developed by the Sixth Committee on Biological Effects of Ionizing Radiations. Objective data on residential radon exposure, population mobility, and tobacco use in the study population were integrated into a Monte-Carlo-type model. Participation rates to radon screening programs were estimated from published data. According to the model used, approximately 10% of deaths due to lung cancer are attributable to residential radon exposure on a yearly basis in Quebec. In the long term, the promotion of a universal screening program would prevent less than one death/year on a province-wide scale (0.8 case; IC 99%: -3.6 to 5.2 cases/year), for an overall reduction of 0.19% in radon-related mortality. Reductions in mortality due to radon by (1) the implementation of a targeted screening program in the region with the highest concentrations, (2) the promotion of screening on a local basis with financial support, or (3) the realization of systematic investigations in primary and secondary schools would increase to 1%, 14%, and 16.4%, respectively, in the each of the populations targeted by these scenarios. Other than the battle against tobacco use, radon screening in public buildings thus currently appears as the most promising screening policy for reducing radon-related lung cancer.

Radon carcinogenesis: risk data and cellular hits

Abundant epidemiological data are now available (2008) on the human lung cancer response for lifetime radon gas exposure to residential concentrations of 100 Bq m(-3), equal to 22 working level months over 40 y. We combined published pooled epidemiological data and dosimetric calculations of alpha particle hits to target basal or mucous cell nuclei in bronchial epithelium. This yields an estimate that about 10,000 basal nuclei (target) cell hits per cm2 per person over a lifetime are involved in radon-related lung cancer. The DNA target cell area (cross section) for a hit is about 2 bp. The present epidemiology indicates that 1000 persons need to be exposed to this hit rate for observable cancers to be detected. The mechanism proposed is that the extensive prior DNA damage in smokers, followed by alpha particle damage to a critical site in checkpoint genes, accounts for the greater lung cancer response in smokers.

Assessment and prevention of radioactive risk due to 222Radon on University Premises in Genoa, Italy.

From October 2004 to September 2005, Radon222 activity in high-risk indoor spaces used by employees and students at the University of Genoa was measured with CR-39 nuclear track detectors. The mean concentration in winter (78.9 Bq/m3 +/- 74.92 S.D.) was low in relation to the microenvironment considered. When data were broken down by type and location of the spaces, no significant differences were found, despite the fact that the Genoa conurbation lies on soil of variable geological composition. The dose absorbed by employees was 0.42 mSv/year, with a relative risk of 4.2/1000 cases of Radon-related lung cancer. The dose absorbed by students was 0.28 mSv/year, with a relative risk of 2.5/1000 cases of Radon-related lung cancer. The level of radon activity detected never exceeded the limit of 500 Bq/m3 established by Italian law. Nevertheless, the value of the compound uncertainty index suggested that the real level of Radon contamination could have exceeded 400 Bq/m3 in selected spaces, a value requiring annual concentration tests.

Lung cancer risk among German male uranium miners: a cohort study, 1946–1998

From 1946 to 1990 extensive uranium mining was conducted in the southern parts of the former German Democratic Republic. The overall workforce included several 100 000 individuals. A cohort of 59 001 former male employees of the Wismut Company was established, forming a large retrospective uranium miners' cohort for the time period 1946–1998. Mean duration of follow-up was 30.5 years with a total of 1 801 630 person-years. Loss to follow-up was low at 5.3%. Of the workers, 16 598 (28.1%) died during the study period. Based on 2388 lung cancer deaths, the radon-related lung cancer risk is evaluated. The excess relative risk (ERR) per working level month (WLM) was estimated as 0.21% (95% CI: 0.18–0.24). It was dependent on time since exposure and on attained age. The highest ERR/WLM was observed 15–24 years after exposure and in the youngest age group (<55 years of age). While a strong inverse exposure-rate effect was detected for high exposures, no significant association was detected at exposures below 100 WLM. Excess relative risk /WLM was not modified by duration of exposure. The results would indicate the need to re-estimate the effects of risk modifying factors in current risk models as duration of exposure did not modify the ERR/WLM and there was only a modest decline of ERR/WLM with increasing time since exposure.

An alternate characterization of hazard in occupational epidemiology: years of life lost per years worked.

Standardized mortality ratios (SMRs) and other measures of relative risk by themselves may not suffice as descriptors of occupational hazards for many audiences including decision-makers and those at direct risk from hazardous work. To explore other approaches, we calculated excess years of potential life lost and excess lifetime risk for both lung diseases and fatal injuries in a cohort of uranium miners with historical records of exposure to radon gas. We used relatively simple life table (SMR) methods and also analyzed lung cancer mortality with Poisson regression methods permitting control for smoking. Among uranium miners hired after 1950, whose all-cause SMR was 1.5, 28 percent would experience premature death from lung diseases or injury in a lifetime of uranium mining. On average, each miner lost 1.5 yr of potential life due to mining-related lung cancer, or almost 3 months of life for each year employed in uranium mining. As a consequence of all excess lung disease and injury risks combined, a year of mining was associated with 5.9 months loss of potential life. For each year actually working underground, miners lost more than 8 months of potential life. When controlled for smoking (and healthy worker effect) with Poisson regression, the estimates for radon-related lung cancer effects were slightly larger. Although chronic disease deaths dominated in excess years of life lost (due to radon, silica and possibly other exposures), more years were lost on average per individual injury death (38 yr), than per excess lung cancer (20 yr) or other lung disease death (18 yr). Fatal-injury dominated the potential years of life lost up to about age 40. Years of life lost per years employed provides another, more intuitive summary of occupational mortality risk.

Exposure to atmospheric radon.

We measured radon (222Rn) concentrations in Iowa and Minnesota and found that unusually high annual average radon concentrations occur outdoors in portions of central North America. In some areas, outdoor concentrations exceed the national average indoor radon concentration. The general spatial patterns of outdoor radon and indoor radon are similar to the spatial distribution of radon progeny in the soil. Outdoor radon exposure in this region can be a substantial fraction of an individual's total radon exposure and is highly variable across the population. Estimated lifetime effective dose equivalents for the women participants in a radon-related lung cancer study varied by a factor of two at the median dose, 8 mSv, and ranged up to 60 mSv (6 rem). Failure to include these doses can reduce the statistical power of epidemiologic studies that examine the lung cancer risk associated with residential radon exposure.

Exposure to Atmospheric Radon

We measured radon (222Rn) concentrations in Iowa and Minnesota and found that unusually high annual average radon concentrations occur outdoors in portions of central North America. In some areas, outdoor concentrations exceed the national average indoor radon concentration. The general spatial patterns of outdoor radon and indoor radon are similar to the spatial distribution of radon progeny in the soil. Outdoor radon exposure in this region can be a substantial fraction of an individual's total radon exposure and is highly variable across the population. Estimated lifetime effective dose equivalents for the women participants in a radon-related lung cancer study varied by a factor of two at the median dose, 8 mSv, and ranged up to 60 mSv (6 rem). Failure to include these doses can reduce the statistical power of epidemiologic studies that examine the lung cancer risk associated with residential radon exposure.

Effects of radon mitigation vs smoking cessation in reducing radon-related risk of lung cancer.

The purpose of this paper is to provide smokers with information on the relative benefits of mitigating radon and quitting smoking in reducing radon-related lung cancer risk. The standard radon risk model, linked with models characterizing residential radon exposure and patterns of moving to new homes, was used to estimate the risk reduction produced by remediating high-radon homes, quitting smoking, or both. Quitting smoking reduces lung cancer risk from radon more than does reduction of radon exposure itself. Smokers should understand that, in addition to producing other health benefits, quitting smoking dominates strategies to deal with the problem posed by radon.

Effects of residential mobility on individual versus population risk of radon-related lung cancer: Warner KE, Courant PN, Mendez D. Dept. Health Management and Policy, School of Public Health, University of Michigan, 103 Observatory, Ann Arbor, MI 48109-2029. Environ Health Perspect 1995; 103:1144–1149

Effects of residential mobility on individual versus population risk of radon-related lung cancer: Warner KE, Courant PN, Mendez D. Dept. Health Management and Policy, School of Public Health, University of Michigan, 103 Observatory, Ann Arbor, MI 48109-2029. Environ Health Perspect 1995; 103:1144–1149