Long-term Radon Exposure Research Articles

Radon Exposure Is Associated with Breast Cancer Risk: A Long-Term Population-Based Study from Finland

Abstract Background Radon is a common environmental carcinogen. It is not known whether radon exposure and breast cancer risk are associated at the population level. Methods Women continuously living in Finland during the 1987-2016 period were linked to municipality-level indoor radon data annually to estimate their cumulative radon exposure over 30 years. Breast cancer incidence was observed over five years from 2017 onwards. Association between radon exposure and breast cancer incidence was assessed using conditional Cox models adjusted for family history of breast cancer, reproductive history, and socio-demographic covariates. Population attributable fractions (PAF) of breast cancer due to radon exposure were estimated. Robustness analyses were conducted in the population who lived only in houses. Results Among 1,335,947 women, 20,067 breast cancer cases were observed during a median follow-up period of 4.9 years. Among women who were exposed to high levels of radon (>100 Bq/m3), overall breast cancer incidence was 10% higher (Hazard ratio 1·10 [95% CI 1·05-1·16]), duct carcinoma incidence was 6% higher (1·06 [1·00-1·13]), lobular carcinoma incidence was 8% higher (1·08 [0·94-1·23]), and the incidence of other morphological sub-types was 34% higher (1·34 [1·17-1·53]) than among other women. Robust associations with overall breast cancer incidence (1·12 [1·05-1·20]) and the incidence of morphological sub-types in the house sample. Correspondingly, suggestive dose-response associations were observed. Conclusions High radon exposure is associated with elevated breast cancer risk at the population level, and this relationship is independent of well-established risk factors. Key messages • This study investigates the association between long-term radon exposure and breast cancer incidence based on national register data. • High radon exposure is robustly associated with breast cancer risk in general Finnish population.

Alteration of genome-wide DNA methylation in non-uranium miners induced by high level radon exposure.

In China, according to statistics about underground non-uranium mine radon levels, 15% exceed the national standard intervention level of 1000Bq/m3, and some mines may exceed 10,000Bq/m3. The relationship between radon exposure in underground miners and lung cancer has already been established, but the mechanisms and biological processes underlying it are poorly understood. In order to identify the genome-wide DNA methylation profile associated with long-term radon exposure, we performed the Infinium Human Methylation 850K BeadChip measurement in whole blood samples obtained from 15 underground non-uranium miners and 10 matched aboveground control workers. Radon concentrations in the air of workplaces and living environments were measured by CR-39 radon detectors, and annual effective doses were calculated using the detection data. Under the high radon concentration with an average value of 12,700Bq·m-3, a total of 165 significant differentially methylated positions (127 hypermethylated sites and 38 hypomethylated sites) annotated to 71 genes were identified in underground miners (|Δβ| ≥ 0.10, p<0.05), and the average DNA methylation level of 165 DMPs was significantly higher than that of the control workers. Most DMPs were found on chromosome 1, and approximately one-quarter of them were located in genomic promoter regions. Through bioinformatics analysis and pyrosequencing validation, five candidate genes differentially methylated by radon, including TIMP2, EMP2, CPT1B, AMD1 and SLC43A2 were identified. GO and KEGG analysis implicated that long term radon exposure could induce the lung cancer related biological processes such as cell adhesion and cellular polarity maintenance. Our study provides evidence for the alterations of genome-wide DNA methylation profiles induced by long-term high level radon exposure, and new insights into searching for carcinogenic biomarkers of high radon exposure in future studies.

A national comparison between the collocated short- and long-term radon measurements in the United States.

Knowing the geographical and temporal variation in radon concentrations is essential for assessing residential exposure to radon, the leading cause of lung cancer in never-smokers in the United States. Tens of millions of short-term radon measurements, which normally last 2 to 4 days, have been conducted during the past decades. However, these massive short-term measurements have not been commonly used in exposure assessment because of the conflicting evidence regarding their correlation with long-term measurements, the gold standard of assessing long-term radon exposure. We aim to evaluate the extent to which a long-term radon measurement can be predicted by a collocated short-term radon measurement under different conditions. We compiled a national dataset of 2245 pairs of collocated short- and long-term measurements, analyzed the predictability of long-term measurements with stratified linear regression and bootstrapping resampling. We found that the extent to which a long-term measurement can be predicted by the collocated short-term measurement was a joint function of two factors: the temporal difference in starting dates between two measurements and the length of the long-term measurement. Short-term measurements, jointly with other factors, could explain up to 79% (0.95 Confidence Interval [CI]: 0.73-0.84) of the variance in seasonal radon concentrations and could explain up to 67% (0.95 CI: 0.52-0.81) of the variance in annual radon concentrations. The large proportions of variance explained suggest that short-term measurement can be used as convenient proxy for seasonal radon concentrations. Accurate annual radon estimation entails averaging multiple short-term measurements in different seasons. Our findings will facilitate the usage of abundant short-term radon measurements, which have been obtained but was previously underutilized in assessing residential radon exposure. Tens of millions of short-term radon measurements have been conducted but underutilized in assessing residential exposure to radon, the greatest cause of lung cancer in non-smokers. We investigate the correlations between collocated short- and long-term measurements in 2245 U.S. buildings and find that short-term measurements can explain ~75% of the variance in subsequent long-term measurements in the same buildings. Our results can facilitate the usage of massive short-term radon measurements that have been conducted to estimate the spatial and longitudinal distribution of radon concentrations, which can be used in epidemiological studies to quantify the health effects of radon.

Proteomic and miRNA profiling of radon-induced skin damage in mice: FASN regulated by miRNAs.

Radon is a naturally occurring radioactive gas and considered as a serious carcinogen to humans. Continuous radioactive decay of this gas emits high-energy alpha particles. Long-term radon exposure induces oxidative stress and inflammatory response, which results in chronic lung diseases. However, biological effects after radon exposure in other organs have been rarely reported. As the outermost organ of the human body, the skin suffers from environmental damage to agents such as air pollution. Epidemiological studies indicated that areas with high level of radon had a high incidence of skin cancer. However, whether radon exposure induces skin damage has not been reported yet. In this study, we established a radon-exposed mouse model and found that radon exposure affected the structure of skin tissues, which was manifested by inflammatory cell infiltration and skin atrophy. Using proteomic approach, we found 45 preferentially expressed proteins in 60 Working Level Months (WLM) group and 314 preferentially expressed proteins in 120 WLM group from radon-exposed skin tissues. Through microRNA (miRNA) sequencing profiling analysis, 57 dysregulated miRNAs were screened between the control and radon-treated mouse skin. By integrating the dysregulated proteins and miRNAs, radon-induced fatty acid synthase (FASN) was investigated in greater detail. Results showed that FASN was regulated by miR-206-3p and miR-378a-3p and involved in the pathogenesis of radon-induced skin damage. Overexpression of FASN inhibited the proliferation, and induced in WS1 cells. Our present findings illustrate the molecular change during radon-induced skin damage and the potential role of FASN during this process.

Repeated radon exposure induced lung damage via oxidative stress-mediated mitophagy in human bronchial epithelial cells and mice

This study aimed to investigate the potential molecular mechanism underlying radon-induced lung damage. Our results showed that long-term radon exposure induced mitochondrial damage and redox imbalance in BEAS-2B cells and a time-dependent lung pathological injury in mice. The activation of Nrf-2 and its down-stream antioxidants, and the gene expression of the indicated markers at different stages of autophagy were found to be induced with the increasing of radon exposure time. Changes in the gene expression of PINK-1, Parkin, and p62 induced by radon showed differences in mechanisms of mitophagy activation and profiles of autophagic flux between BEAS-2B cells and mice. Our findings not only demonstrated that long-term radon exposure induced damages to bronchial epithelial cells and the mice lung through increasing oxidative stress, decreasing mitochondrial function and activating mitophagy with different profiles of autophagic flux, but also revealed Nrf-2 as a central regulator of mitochondrial homeostasis and lung damage.

Impact of temporal variability of radon concentration in workplaces on the actual radon exposure during working hours

For workplaces where significant diurnal variations in radon concentrations are likely, measurements to evaluate average radon concentration during working hours could be useful for planning an optimized protection of workers according to the 2013/59/Euratom Directive. However, very few studies on this subject, generally limited to periods of few weeks, have been published. Therefore, a study has been conducted to evaluate the actual long-term radon exposure during working hours for a sample of 33 workplaces of four different types (postal offices, shops, restaurants, municipal offices), mainly located at the ground floor, and with expected considerable air exchange rate occurring during working hours due to frequent entrance/exit of persons or mechanical ventilation. The results show that the difference between the average radon level during working hours and that one during the whole day is about 20% on average and ranges from 0 to 50%. These observed differences, generally smaller compared with those found in other similar studies, are nearly the same if the analysis is restricted to workplaces with annual radon level higher than 300 Bq m–3, and therefore natural or mechanical ventilation normally present during working hours of the monitored workplaces cannot be considered an effective mitigation measure. However, the costs and time-response characteristics of the active monitors, as those used for the present study, will probably allow using more frequently a similar measurement strategy in workplaces.

Protection of melatonin against long-term radon exposure-caused lung injury.

Radon is one of the major pathogenic factors worldwide. Recently, epidemiological studies have suggested that radon exposure plays an important role in lung injury, which could further cause cancer. However, the toxic effects and underlying mechanism on lung injury are still not clear. Here, we identified the detailed toxic effects of long-term radon exposure. Specifically, the manifestations were inflammatory response and cell apoptosis in dose- and time-dependent manners. In detail, it caused the mitochondrial dysfunction and oxidative stress as determined by the abnormal levels of mitochondrial DNA copy number, adenosine triphosphate, mitochondrial membrane potential, superoxide dismutase, and cycloxygenase-2. Furthermore, we found that melatonin treatment ameliorated mitochondrial dysfunction and attenuated the levels of oxidative stress caused by long-term radon exposure, which could further inhibit the lung tissue apoptosis as determined by the decreased levels of cleaved caspase 3. Our study would provide potential therapeutic application of melatonin on lung tissue injury caused by long-term radon exposure.

SDHA-mediated Warburg effect in malignantly transformed human bronchial epithelial cells following long-term exposure to radon.

Radon and its progeny have been classified as human class I carcinogens by the IARC. However, the mechanisms by which radon induces lung and other cancers, especially the radon-induced Warburg effect, have not been fully elucidated. The aim of this study was to investigate the role of the succinate dehydrogenase subunit A (SDHA)-mediated Warburg effect in (human bronchial epithelial) BEAS-2B cells with malignant transformations induced by long-term radon exposure. Soft agar colony formation and MMP-9 were increased following radon-induced malignant transformation. Additionally, we observed the Warburg effect in BEAS-2B cells following long-term radon exposure, evidenced by increases in the levels of glucose uptake, lactate, and lactate dehydrogenase (LDH). Following radon exposure, the expression of SDHA was decreased, while the levels of HIF-1α and hexokinase-2 (HK2) were increased. Our findings suggested that the SDHA-associated pathway may be involved in mediating the Warburg effect in radon-induced malignant transformation of BEAS-2B.

The Disease Burden of Lung Cancer Attributable to Residential Radon Exposure in Korean Homes

BackgroundResidential radon exposure is known to be an important risk factor for the development of lung cancer. The objective of this study was to calculate the disease burden of lung cancer attributable to residential radon exposure in Korea.MethodsWe calculated the national exposure level using Korean national radon survey data from 2011 to 2014, and house structure distribution data from each administrative region. Using the exposure-risk function, the population attributable fraction (PAF) was calculated and applied to calculate the disease burden for lung cancer attributable to residential radon exposure.ResultsResidential radon exposure levels were the highest, at 116.4 ± 50.4 Bq/m3 (annual mean radon concentration ± standard deviation) in detached houses, followed by 74.1 ± 30.0 Bq/m3 in the multi-family dwellings, and 55.9 ± 21.1 Bq/m3 in apartments. The PAF for lung cancer, due to long-term radon exposure in Korean homes, was 6.6% and 4.7% in men and women, respectively. The total disease burden of lung cancer attributable to residential radon exposure was 14,866 years of life lost (YLL) and 1,586 years lost due to disability (YLD) in 2013. Overall, 1,039 deaths occurred due to residential radon exposure, of which 828 were in men and 211 in women.ConclusionThe smoking rate of men in Korea exceeded 70% in the 1990s, and is still near 40%. Although the size of the effect varies depending on the estimation method, it is a critical aspect as a risk factor of lung cancer because of the synergistic relationship between smoking and radon exposure. Because the Korean society is rapidly aging, population who were formerly heavy-smokers are entering a high-risk age of lung cancer. Therefore, it is necessary to inform the public about the health benefits of reduced radon exposure and to strengthen the risk communication.

Air change rates and radon accumulation in rooms with various levels of window and door closure

Dwellings in Israel must include a residential protected room made of thick concrete slabs and walls, with an extremely airtight window and outward opening extremely airtight steel door. An inward opening regular door is applied for everyday usage. Being multipurpose, the residential protected room raised concern regarding long-term radon exposure. This article presents the stage of air change rate investigation (using SF6 as tracer gas) and radon monitoring in a multidisciplinary research performed by two teams. It comprised six residential protected rooms in a tall unoccupied building, including various scenarios of window and door closure. The teams established a common theoretical model and addressed sensitivity to differences in assumptions and methods of analysis. Similar orders of magnitude of air change rates and free surface exhalation rates were obtained, but with nonnegligible discrepancies between specific values. Tracer gas method results were more sensitive to calculation assumptions and radon monitoring results to measurement uncertainties. Measured air change rates were as follows: fully sealed residential protected room: &lt;0.03 ACH (air changes per hour); closed window and regular door: &lt;0.25 ACH; tilted window and closed door: 1–3 ACH; one component open and the other closed: 3–20 ACH; and both components somewhat open: 20–100 ACH. It was shown that expected maximal radon concentrations in a residential protected room under conditions of regular usage or emergency protection would not reach the limit value of 200 Bq/m3.

An Extended Study on the Correlation between 210Pb in Household Dust and Indoor Radon Concentration

Radon and its progeny have been identified as the second leading cause of lung cancer after tobacco smoking. Radon decays to a long-lived isotope, 210Pb, with a half-life of about 22 years. Measuring concentrations of 210Pb in household dust could be an alternative method of determining indoor radon levels. A previous study conducted in 2008 demonstrated that 210Pb concentrations in household dust correlate reasonably well to radon concentrations in homes. To confirm the viability of this retrospective method, a field experiment was repeated in 2010 to further study the correlation between 210Pb in household dust and indoor radon concentration. The results showed that 210Pb is a reasonably good indicator of long-term radon exposure indoors when dust samples collected are representative of household dust in a house.

210Pb concentration in household dust: a potential indicator of long-term indoor radon exposure

Radon decays to a long-lived isotope 210Pb with a half-life of about 22 years. Measuring concentrations of 210Pb in household dust could be an alternative method of determining indoor radon levels. This novel method for estimating long-term radon concentration was explored in over a hundred Canadian residential homes. The results demonstrate that 210Pb concentrations in household dust relate reasonably well to radon concentrations in homes.

Radon-Induced Proteomic Profile of Lung Tissue in Rats

The aim of this study was to investigate the differential expression of proteins in lung of rats following long-term exposure to radon. The total proteins of lung tissue from Wistar rats exposed to radon for cumulative doses up to 100, 200, or 400 WLM (working level months) were isolated by two-dimensional electrophoresis (2-DE) and analyzed with ImageMaster 2D Platinum software. Comparison of the 2-DE images between the control and radon-exposed groups resulted in 14 upregulated and 9 downregulated protein spots, of which 15 were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) or matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). The simultaneous up-expressions of RAGE and S100A6 indicated that both proteins might be applied as biomarkers for lung injury induced by long-term radon exposure.

Adverse Effects Attributed to Long-term Radon Inhalation in Rats

The aim of this study was to investigate the adverse effect of long-term radon exposure on lung and blood cells in rats exposed to different radiation doses. Sprague-Dawley rats were exposed to radon for cumulative doses up to 66, 111, and 174 WLM (work level month). Total number and differential cells counts were determined in the bronchoalveolar lavage fluid (BALF) and the peripheral blood, as well as the activity of lactate dehydrogenase (LDH) and levels of glutathione (GSH) and total protein. DNA damage and interleukin (IL)-6 mRNA expression in BALF cells and peripheral blood mononuclear cells (PBMC) were detected by single cell gel electrophoresis (SCGE) and reverse-transcription polymerase chain reaction (RT-PCR), respectively. The results showed that radon-exposed lymphocytes were significantly lower and granulocytes higher in BALF compared to blood in exposed groups. The distance of DNA migration in the BALF and PBMC increased in a dose-dependent manner. A positive correlation between the PBMC and BALF cells in terms of DNA damage was noted. These findings suggested that PBMC might be used as a surrogate for BALF cells and thus the easier non-invasive ability to obtain PBMC may be useful in detection of lung DNA damage induced by radon.

Risk of lung cancer and residential radon in China: pooled results of two studies.

Studies of radon-exposed underground miners predict that residential radon is the second leading cause of lung cancer mortality; however, case-control studies of residential radon have not provided unambiguous evidence of an association. Owing to small expected risks from residential radon and uncertainties in dosimetry, large studies or pooling of multiple studies are needed to fully evaluate effects. We pooled data from 2 case-control studies of residential radon representing 2 large radon studies conducted in China. The studies included 1050 lung cancer cases and 1996 controls. In the pooled data, odds ratios (OR) increased significantly with greater radon concentration. Based on a linear model, the OR with 95% confidence intervals (CI) at 100 Becquerel/cubic-meter (Bq/m(3)) was 1.33 (1.01,1.36). For subjects resident in the current home for 30 years or more, the OR at 100 Bq/m(3) was 1.32 (1.07,1.91). Results across studies were consistent with homogeneity. Estimates of ORs were similar to extrapolations from miner data and consistent with published residential radon studies in North American and Europe, suggesting long-term radon exposure at concentrations found in many homes increases lung cancer risk.

Estimating the attributable risk of residential radon among nonsmoking women: Initial results and methodologic challenges

A population-based, case-control study of incident lung cancer among women in Missouri (United States) who were lifetime nonsmokers and long-term exsmokers was conducted between 1986 and 1992. The study included 538 lung cancer cases and 1183 population-based, age matched controls. Information on lung cancer risk factors was obtained by interviewing cases, next-of-kin of cases, and controls. Year-long radon measurements were also sought in every dwelling occupied for the previous 5–30 y. The Missouri study was among the first studies specifically-designed to evaluate the effects of residential radon on lung cancer risk. The mean radon level found in homes was 1.6 pCi/L. This level of radon exposure is somewhat higher than that observed in the United States as a whole (mean 1.25 pCi/L). A small nonsignificant risk was found for study subjects exposed to a median domestic radon concentration of 4 pCi/L (25 y time-weight average). Since only a small fraction of the population is exposed at this level, it is estimated that the population attributable risk (PAR) for domestic radon is between 1 and 4% in Missouri. The growing body of residential studies has not clearly shown an elevation in lung cancer risk due to low-level, long-term radon exposure. It may be difficult to demonstrate a statistically significant increase in risk due in part to the inherent methodologic difficulties associated with assessing the potential carcinogenic effect of low-level radon exposure, errors in reconstructing past radon exposures, and population mobility which tends to homogenize exposures. A complementary method of radon exposure measurement, now being used in a second epidemiologic evaluation of lung cancer in Missouri, which uses heirloom glass to assess actual historic cumulative dose, is discussed, and may help strengthen future studies.

Long-Lived Radon Decay Products as a Long-Term Radon Exposure Indicator

Long-Lived Radon Decay Products as a Long-Term Radon Exposure Indicator

Long-Lived Radon Decay Products as a Long-Term Radon Exposure Indicator

Abstract The different members of the uranium decay series have distinct roles to play in the scenario of indoor radon. The 222Rn gas is the airborne carrier of the dose giving short-lived decay products. These transform into long-lived daughters (LRnD) of low activity, useful as retrospective radon tracers. Porous objects constitute volume traps for LRnD via radon diffusion, while surfaces trap LRnD through alpha recoil implantation. Only when the build-up of LRnD activity proceeds undisturbed over many years, do we have a system which is potentially useful for retrospective radon/radon daughter exposure studies. The feasibility of using LRnD in humans and in volume and surface traps as radon retrospective monitors is discussed. It is concluded that only surface implantation sinks are potentially well suited for long-term studies at radon levels met in dwellings.

The Use of Computed Radon Entry Rates to Understand Radon Concentration in Buildings

The central role played by basement depressurization in drawing radon-contaminated soil gas into a structure has been demonstrated by calculating the radon entry rate from radon concentration and air infiltration measurements at different levels of basement depressurization in a single-family research house. The radon entry rate is found to be a linear function of basement depressurization in this house which indicates that the flow of soil gas into the structure is laminar. The radon entry rates calculated before and after using a mitigation procedure is shown to provide a better measure of the mitigation efficacy than the standard before and after mitigation radon measurements in a research house. In addition, an analysis of the possible flow characteristics of soil gas and uncontaminated air into a basement indicates that any attempt to predict long-term average radon exposure from short-term screening measurements will only be possible under severely restricted conditions.

Increased risk for small cell lung cancer following residential exposure to low-dose radon: a pilot study.

Alpha track radon detectors were placed in the homes of 35 lung cancer patients and 35 matched controls for a period of 8 to 10 mo. Twenty lung cancer patients had small cell lung carcinoma; 11 had adenocarcinoma, 2 had squamous cell carcinoma, and 2 had unclassified carcinoma among 15 nonsmokers. Mean overall living on ground level was significantly higher in the group with small cell lung carcinoma (50 y +/- 15) than among controls (33 y +/- 19); the adjusted odds ratio for lung cancer was 5.2 (90% confidence interval [90% CI] = 1.1-24.9) per decade of living on the ground floor for the group with small cell lung carcinoma. Radon exposure of more than 1.0 pci/l in the group with small cell lung carcinoma was associated with increased risk of lung cancer, although it did not reach statistical significance [odds ratio = 1.5 (90% CI = 0.4-5.4)], adjusting for differences in smoking habits. Our study supports the presence of a differentially increased risk for small cell lung carcinoma following long-term radon exposure.