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.

Evaluating county-level lung cancer incidence from environmental radiation exposure, PM2.5, and other exposures with regression and machine learning models.

Characterizing the interplay between exposures shaping the human exposome is vital for uncovering the etiology of complex diseases. For example, cancer risk is modified by a range of multifactorial external environmental exposures. Environmental, socioeconomic, and lifestyle factors all shape lung cancer risk. However, epidemiological studies of radon aimed at identifying populations at high risk for lung cancer often fail to consider multiple exposures simultaneously. For example, moderating factors, such as PM2.5, may affect the transport of radon progeny to lung tissue. This ecological analysis leveraged a population-level dataset from the National Cancer Institute's Surveillance, Epidemiology, and End-Results data (2013-17) to simultaneously investigate the effect of multiple sources of low-dose radiation (gross [Formula: see text] activity and indoor radon) and PM2.5 on lung cancer incidence rates in the USA. County-level factors (environmental, sociodemographic, lifestyle) were controlled for, and Poisson regression and random forest models were used to assess the association between radon exposure and lung and bronchus cancer incidence rates. Tree-based machine learning (ML) method perform better than traditional regression: Poisson regression: 6.29/7.13 (mean absolute percentage error, MAPE), 12.70/12.77 (root mean square error, RMSE); Poisson random forest regression: 1.22/1.16 (MAPE), 8.01/8.15 (RMSE). The effect of PM2.5 increased with the concentration of environmental radon, thereby confirming findings from previous studies that investigated the possible synergistic effect of radon and PM2.5 on health outcomes. In summary, the results demonstrated (1) a need to consider multiple environmental exposures when assessing radon exposure's association with lung cancer risk, thereby highlighting (1) the importance of an exposomics framework and (2) that employing ML models may capture the complex interplay between environmental exposures and health, as in the case of indoor radon exposure and lung cancer incidence.

A cohort analysis of residential radon exposure and melanoma incidence in Switzerland.

Radon is a radioactive noble gas found in Earth's crust. It accumulates in buildings, and accounts for approximately half the ionizing radiation dose received by humans. The skin is considerably exposed to ionizing radiation from radon. We aimed to evaluate the association between residential radon exposure and melanoma and squamous cell carcinoma incidence. The study included 1.3 million adults (20 years and older) from the Swiss National Cohort who were residents of the cantons of Vaud, Neuchâtel, Valais, Geneva, Fribourg, and Ticino at the study baseline (December 04, 2000). Cases of primary tumours of skin (melanoma and squamous cell carcinoma) were identified using data from cantonal cancer registries. Long-term residential radon and ambient solar ultraviolet radiation exposures were assigned to each individual's address at baseline. Cox proportional hazard models with age as time scale, adjusted for canton, socioeconomic position, demographic data available in the census, and outdoor occupation were applied. Total and age specific effects were calculated, in the full population and in non-movers, and potential effect modifiers were tested. In total 4937 incident cases of melanoma occurred during an average 8.9 years of follow-up. Across all ages, no increased risk of malignant melanoma or squamous cell carcinoma incidence in relation to residential radon was found. An association was only observed for melanoma incidence in the youngest age group of 20-29 year olds (1.68 [95% CI: 1.29, 2.19] 100 Bq/m3 radon). This association was mainly in women, and in those with low socio-economic position. Residential radon exposure might be a relevant risk factor for melanoma, especially for young adults. However, the results must be interpreted with caution as this finding is based on a relatively small number of melanoma cases. Accumulation of radon is preventable, and measures to reduce exposure and communicate the risks remain important to convey to the public.

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 1000 Bq/m3, and some mines may exceed 10,000 Bq/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 850 K 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 12,700 Bq·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 (|Δß| ≥ 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.

Elevated radon level in drinking water of Ajodhya Hill Area of West Bengal, India: probable health impact on lung and stomach.

A screening survey has been carried out to measure the radon concentration in drinking water at various locations of Ajodhya hill and surrounding areas in Purulia district of West Bengal, India, using AlphaGUARD radon monitor. The obtained 222Rn concentration in ground water varies from 5.71 ± 0.29 to 579.47 ± 23.18 Bq/l with an average of 110.00 ± 6.61 Bq/l. Comparison between our results with the internationally recommended reference levels reveals that drinking of water from the majority of these tube-wells can pose significant health risks to the local people. Correlation study indicates that tube-well depth has significant influence on the radon level in water samples. Using 60 l/yr and 1642.50 l/yr water consumption estimated annual effective radon doses for most of the samples (almost 70% and 96%, respectively) are high compared to the World Health Organization (WHO) and the European Union (EU) Commission prescribed reference dose limit of 100 µSv/yr. Also, the evaluated Excess Lifetime Cancer Risk (ELCR) values associated with the tube-wells are showing serious threat to the health of the locals.The primary goal of this work is to develop a radon profile map of this area and to find out the possible reasons behind the elevated radon level in ground water. This type of work may play a very crucial role to aware the locals in perspective of human exposure to radon. The local health officials and the water quality regulators of India are requested to take necessary steps for protecting the local people from water radon hazard.

Oxidative genomic damage in humans exposed to high indoor radon levels in Northeast Brazil.

Radon gas inhalation is the main source of exposure to ionizing radiation by humans. There is still lack in knowledge concerning the chronic and indirect effects of exposure to this carcinogenic factor. Therefore, the aim of this work is to analyze the levels of oxidative genomic damage in inhabitants of a medium-high background radiation area (HBRA) (N = 82) in Northeastern Brazil and compare them with people living in a low background radiation area (LBRA) (N = 46). 8-hydroxy-2-deoxyguanosine (8-OHdG) was quantified in urine, Ser326Cys polymorphism was determined in the hOGG1 gene and indoor radon was measured. HBRA houses had 6.5 times higher indoor radon levels than those from LBRA (p-value < 0.001). The 8-OHdG mean (95% confidence interval) were significantly different, 8.42 (5.98-11.9) ng/mg creatinine and 29.91 (23.37-38.30) ng/mg creatinine for LBRA and HBRA, respectively. The variables representing lifestyle and environmental and occupational exposures did not have a significant association with oxidized guanosine concentrations. On the other hand, lower 8-OHdG values were observed in subjects that had one mutant allele (326Cys) in the hOGG1 gene than those who had both wild alleles (Ser/Ser (p-value < 0.05). It can be concluded that high radon levels have significantly influenced the genome oxidative metabolism and hOGG1 gene polymorphism would mediate the observed biological response.

Experimental Setups for In Vitro Studies on Radon Exposure in Mammalian Cells-A Critical Overview.

Naturally occurring radon and its short lived progeny are the second leading cause of lung cancer after smoking, and the main risk factor for non-smokers. The radon progeny, mainly Polonium-218 (218Po) and Polonium-214 (214Po), are responsible for the highest dose deposition in the bronchial epithelium via alpha-decay. These alpha-particles release a large amount of energy over a short penetration range, which results in severe and complex DNA damage. In order to unravel the underlying biological mechanisms which are triggered by this complex DNA damage and eventually give rise to carcinogenesis, in vitro radiobiology experiments on mammalian cells have been performed using radon exposure setups, or radon analogues, which mimic alpha-particle exposure. This review provides an overview of the different experimental setups, which have been developed and used over the past decades for in vitro radon experiments. In order to guarantee reliable results, the design and dosimetry of these setups require careful consideration, which will be emphasized in this work. Results of these in vitro experiments, particularly on bronchial epithelial cells, can provide valuable information on biomarkers, which can assist to identify exposures, as well as to study the effects of localized high dose depositions and the heterogeneous dose distribution of radon.

Consequences of changing Canadian activity patterns since the COVID-19 pandemic include increased residential radon gas exposure for younger people.

The COVID-19 pandemic has produced widespread behaviour changes that shifted how people split their time between different environments, altering health risks. Here, we report an update of North American activity patterns before and after pandemic onset, and implications to radioactive radon gas exposure, a leading cause of lung cancer. We surveyed 4009 Canadian households home to people of varied age, gender, employment, community, and income. Whilst overall time spent indoors remained unchanged, time in primary residence increased from 66.4 to 77% of life (+ 1062 h/y) after pandemic onset, increasing annual radiation doses from residential radon by 19.2% (0.97 mSv/y). Disproportionately greater changes were experienced by younger people in newer urban or suburban properties with more occupants, and/or those employed in managerial, administrative, or professional roles excluding medicine. Microinfluencer-based public health messaging stimulated health-seeking behaviour amongst highly impacted, younger groups by > 50%. This work supports re-evaluating environmental health risks modified by still-changing activity patterns.

Radon - occurrence and impact on the health.

Radon is noble, monatomic, radioactive, heavier than the air gas. It is colorless, odorless, tasteless. It exists in natural environment as a result of the decay of radium, and emits mainly alpha radiation and less beta radiation. Residential radon concentrations vary widely by geographic area. The higher concentration of radon is expected globally in the grounds where uranium, radium and thoron are present. Radon may gather in caves, tunnels, mines as well as in other lowestlying spaces, such as basements, and cellars. In accordance with Atomic Law (2000), the reference level for the average annual concentration of radioactive radon in rooms intended for human habitation is 300 Bq/m3. The most dangerous damages caused by ionizing radiation i.e. radon and its derivatives are changes to DNA, which may disturb the functions of cells and in the consequence lead to induction of cancer of respiratory tract, mainly of lungs and also leukaemia. So, the main consequence of exposure to high amount of radon are cancers of respiratory system. Radon enters the human organism mainly through inhaled atmospheric air. Moreover, radon significantly increased a risk of induction cancer in smokers and vice versa, smoking promotes the development of lung cancer after the exposure to radon and its derivatives. Radon may also have beneficial effect on the human body. Therefore it is used in medicine; mainly in radonbalneotherapy i.e. bath treatments, rinsing the mouth and inhalation. Beneficial effects of radon confirms the validity of the theory of radiation hormesis, which assumes that low doses of radiation may stimulate the repair of DNA damage by activation of protective mechanisms, which neutralize free radicals.

Effects of radon exposure on gut microbiota and its metabolites short-chain fatty acids in mice.

Radon (222Rn) is a naturally occurring radioactive gas. Forty percent of the natural radiation to which the human body is exposed comes from radon gas. Long-term exposure to high concentrations of radon induces systemic damage. However, the effect of such exposure on gut microbiota still remains unclear. We explored the effects of radon exposure on gut microbiota and its metabolites short-chain fatty acids (SCFAs) in BALB/c mice by cumulative inhalation of radon at 30, 60, and 120 working level months (WLM). The radon-exposed mice showed slow body weight gain, decreased serum triglycerides and low-density lipoproteins, decreased diversity, lower community structure, and altered abundance of the gut microbiota. Lachnospiraceae, Amaricoccus, and Enterococcus could differentiate the IR30, 60, and 120 WLM groups, respectively. Meanwhile, radon exposure affected the metabolic functions of the gut microbiota, mainly carbohydrate, amino acid, and lipid metabolic pathways. The altered abundance of microbiota and resulting reduced levels of SCFAs may aggravate the damage caused by radon exposure.

Exposure to radon and heavy particulate pollution and incidence of brain tumors.

BACKGROUND: Global incidence for brain tumors varies substantially without explanation. Studies correlating radon exposure and incidence are inconclusive. Particulate pollution has been linked to increased tumor incidence. Particulates may disrupt the blood-brain barrier allowing intracranial exposure to oncogenic radon. We investigated the relationship between exposure to residential radon, particulate pollution, and brain tumor incidence in the United States (US). METHODS: County-level median radon testing results and annual air quality index values were obtained and divided into tertiles. Counties without both values were excluded. Four groups of counties were generated: high particulate/high radon (high/high), high/low, low/high, and low/low. Using incidence data from the Central Brain Tumor Registry of the US (provided by CDC's National Program of Cancer Registries and NCI's SEER), annual age-adjusted incidence rates (AAAIRs) by group were generated by behavior. Incidence rate ratios were calculated to examine for significant differences (α = .05). Poisson regression accounting for possible confounders was conducted. RESULTS: Counties with available data included 83% of the US population. High/high exposure was significantly associated with increased AAAIR of all non-malignant tumors (up to 26% higher, including most meningiomas) even after accounting for potential confounders. An increased AAAIR was noted for all malignant tumors (up to 10% higher), including glioblastoma, but was negated after accounting for demographic/socioeconomic differences. CONCLUSIONS: We present the first report suggesting increased non-malignant brain tumor incidence in regions with high particulate and radon exposure. These findings provide insight into unexplained variation in tumor incidence. Future studies are needed to validate these findings in other populations.

The occurrence of bone and joint cancers and their association with rural living and radon exposure in Iowa.

Primary bone and joint cancers are rare and understudied, yet these neoplasms are difficult to treat and impact all age groups. To explore the long-term changes in the occurrence of bone and joint cancers, patients diagnosed with these neoplasms between 1975 and 2016 were identified in the Surveillance Epidemiology and End Results of the National Cancer Institute of the USA. The age-adjusted incidence (AAIR) and mortality (AAMR) rates were calculated for three decades and compared to AAIR and AAMR in years 1975-1984. By using the population-based cancer registries of the USA, Iowa was identified as a state with increased cases of bone and joint malignancies. The bone and joint cancer cases in Iowa were correlated with the percentage of rural population, the average farmland size, or the residential radon levels. Results demonstrated that the mean AAIR of bone and joint cancers for US female and male patients (< 50 years of age) increased from 0.57 (95% C.I. 0.55-0.63) and 0.76 (95% C.I. 0.69-0.82) for years 1975-1984 to 0.71 (95% C.I. 0.66-0.76) and 0.94 (95% C.I. 0.87-1.07) for years 2005-2014, respectively. The increase in bone and joint cancer cases in Iowa positively correlated with the percentage rural population (R = 0.222, P < 0.02), and the average farmland size (R = 0.236, P < 0.02) but not the radon levels (R = - 0.038, P < 0.7). The findings revealed that patients younger than 50 years of age and those who resided in rural areas and engaged in farming were more likely to be diagnosed with primary bone and joint cancers.

Chromosome aberrations, micronucleus frequency, and catalase concentration in a population chronically exposed to high levels of radon.

PURPOSE: To deepen our knowledge on the effects of high levels of indoor radon exposure, we assessed the frequencies of unstable and stable chromosome aberrations and micronucleus (MN), as well as the concentration of an endogenous antioxidant (catalase, CAT), in blood samples of individuals chronically exposed to high indoor radon concentrations in Indonesia (Tande-Tande sub-village, Mamuju, West Sulawesi). Moreover, we also investigated the occurrence of a radio-adaptive response (RAR) in Tande-Tande sub-village inhabitants using the G2 MN assay. MATERIALS AND METHODS: The frequencies of dicentric (DC), acentric (AF), ring (R), and translocation (Tr) chromosomes in Tande-Tande inhabitants were compared to those in people living in a reference area with low levels of indoor radon levels (Topoyo village, Indonesia). The number of MN per 1000 binucleated cells (BNC) and CAT concentration per total protein was quantified and compared between groups. Lastly, we irradiated (2 Gy) phytohemagglutinin-stimulated samples in vitro and measured the frequency of MN to verify the occurrence of a RAR in Tande-Tande sub-village inhabitants. RESULTS AND CONCLUSION: The frequencies of DC, AF, and Tr did not differ between Tande-Tande inhabitants and control subjects (p = 0.350, 0.521, 0.597). The frequency of MN in Tande-Tande inhabitants was significantly lower than that in the control group (p = 0.006). Similarly, CAT concentration in Tande-Tande inhabitants was also significantly lower than that in the control population (p < 0.001). Significant negative correlations were identified for MN number and CAT concentration versus indoor radon concentration, annual effective dose, or cumulative dose both within groups and when all data were analyzed together. Our findings indicate that, despite the high indoor radon levels, Tande-Tande inhabitants are not under oxidative stress, since this group had lower CAT concentration and MN frequency than those in the control group. The negative correlation between MN frequency and indoor radon concentration, annual effective dose, and cumulative dose suggests the occurrence of an RAR phenomenon in Tande-Tande sub-village inhabitants. This interpretation is also supported by the results of the G2 MN assay, which revealed lower MN frequencies after in vitro irradiation of samples from Tande-Tande sub-village inhabitants than those in samples from the control group (p = 0.0069, for cumulative MN frequency; p = 0.0146, for radiation-induced MN only).

Social factors and behavioural reactions to radon test outcomes underlie differences in radiation exposure dose, independent of household radon level.

Radioactive radon gas inhalation causes lung cancer, and public health strategies have responded by promoting testing and exposure reduction by individuals. However, a better understanding of how radon exposure disparities are driven by psychological and social variables is required. Here, we explored how behavioural factors modified residential radon-related radiation doses incurred by 2390 people who performed a radon test. The average time from first awareness to receiving a radon test outcome was 6.8-25.5 months, depending on behaviour and attitudes. 20.5% displayed radon test urgency that reduced irradiation between awareness and outcome to 1.8 mSv from a typical 3.5 mSv, while 14.8% (more likely to be men) displayed delaying behaviours that increased exposure to 8.0 mSv. Of those with low radon, 45.9% indicated no future testing intention, underscoring the importance of original tests to reliably establish risk. Among people finding high radon, 38% mitigated quickly, 29% reported economic impediments, and 33% displayed delaying behaviours. Economic barriers and delaying behaviours resulted in 8.4 mSv/year or 10.3 mSv/year long term excess exposure, respectively, increasing lifetime risk of lung cancer by ~ 30-40%. Excess radiation doses incurred from behaviour were independent of household radon level, highlighting the strong influence of psychological and socioeconomic factors on radon exposure and lung cancer risks.

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.

Residential Radon and Small Cell Lung Cancer. Final Results of the Small Cell Study.

INTRODUCTION: Residential radon is considered the second cause of lung cancer and the first in never smokers. Nevertheless, there is little information regarding the association between elevated radon levels and small cell lung cancer (SCLC). We aimed to assess the effect of residential radon exposure on the risk of SCLC in general population through a multicentric case-control study. METHODS: A multicentric hospital-based case-control study was designed including 9 hospitals from Spain and Portugal, mostly including radon-prone areas. Indoor radon was measured using Solid State Nuclear Track Detectors at the Galician Radon Laboratory. RESULTS: A total of 375 cases and 902 controls were included, with 24.5% of cases being women. The median number of years living in the measured dwelling was higher than 25 years for both cases and controls. There was a statistically significant association for those exposed to concentrations higher than the EPA action level of 148Bq/m3, with an Odds Ratio of 2.08 (95%CI: 1.03-4.39) compared to those exposed to concentrations lower than 50Bq/m3. When using a dose-response model with 100Bq/m3 as a reference, it can be observed a linear effect for small cell lung cancer risk. Smokers exposed to higher radon concentrations pose a much higher risk of SCLC compared to smokers exposed to lower indoor radon concentrations. CONCLUSIONS: Radon exposure seems to increase the risk of small cell lung cancer with a linear dose-response pattern. Tobacco consumption may also produce an important effect modification for radon exposure.

Does protracted radon exposure play a role in the development of dementia?

Radon is a ubiquitous radioactive gas that decays into a series of solid radioactive decay products. Radon, and its decay products, enter the human body primarily through inhalation and can be delivered to various tissues including the brain through systemic circulation. It can also reach the brain by neuronal pathways via the olfactory system. While ionizing radiation has been suggested as a risk factor of dementia for decades, studies exploring the possible role of radon exposure in the development of Alzheimer's Diseases (AD) and other dementias are sparse. We systematically reviewed the literature and found several lines of evidence suggesting that radon decay products (RDPs) disproportionally deposit in the brain of AD patients with selective accumulation within the protein fractions. Ecologic study findings also indicate a significant positive correlation between geographic-level radon distribution and AD mortality in the US. Additionally, pathologic studies of radon shed light on the potential pathways of radon decay product induced proinflammation and oxidative stress that may result in the development of dementia. In summary, there are plausible underlying biological mechanisms linking radon exposure to the risk of dementia. Since randomized clinical trials on radon exposure are not feasible, well-designed individual-level epidemiologic studies are urgently needed to elucidate the possible association between radon (i.e., RDPs) exposure and the onset of dementia.

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

BACKGROUND: Occupational 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. METHODS: A 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. RESULTS: A 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. CONCLUSION: This 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.

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.

Human Health Impacts of Residential Radon Exposure: Updated Systematic Review and Meta-Analysis of Case-Control Studies.

This study investigated the impact of residential radon exposure on human cancers (i.e., lung cancer and childhood leukemia) through a systematic review and meta-analysis of case−control studies. A total of 9724 articles obtained from electronic databases were assessed; however, only 55 case−control studies were eligible after manually screening and eliminating unnecessary studies. The causal associations were addressed by determining the meta-analysis's estimated size effects (i.e., ORs/RRs) of the meta-analysis. Residential radon was revealed to significantly increase the incidence of lung cancer and childhood leukemia with pooled ORs of 1.38 [1.19; 1.60] (I2 = 90%; p < 0.00001) and 1.43 [1.19; 1.72] (I2 = 0% and p = 0.51), respectively. In addition, subgroup analyses were performed to reduce the heterogeneity of the initial meta-analyses. The results provided strong evidence that inhaling radon in the indoor environments is closely associated with the development of lung cancer and childhood leukemia in patients living in Europe and areas with high radon levels (≥100 Bq/m3).