Environmental Radon Exposure Research Articles

Lung cancer screening for never smokers: current evidence and future directions.

Screening for lung cancer using low-dose computed tomography is an established means for early lung cancer detection in smokers, but the role of screening for never smokers is unclear. In the 13 lung cancer screening studies involving unselected never smokers, detection rates ranged from 0.1% to 1.1% and positive predictive values ranged from 0.4% to 4.5%. In three lung cancer screening studies involving selected never smokers, selection was based primarily on occupational asbestos exposure, environmental radon exposure and family history of lung cancer in first-degree relatives. Detection rates ranged from 0.3% to 2.6%, and positive predictive values ranged from 0.7% to 15%. Also, 80%-100% of lung cancer cases discovered by screening were early stage, with limited data suggesting survival benefit. Lung cancer screening for never smokers with selected risk factors may achieve detection rates similar to those of screening for high-risk ever smokers. However, further research on optimal subject selection, alternative screening methods and clinical/economic outcomes is needed.

Low dose environmental radon exposure and breast tumor gene expression

BackgroundThe International Agency for Research on Cancer classified radon and its decay-products as Group-1-human-carcinogens, and with the current knowledge they are linked specifically to lung cancer. Biokinetic models predict that radon could deliver a carcinogenic dose to breast tissue. Our previous work suggested that low-dose radon was associated with estrogen-receptor (ER)-negative breast cancer risk. However, there is limited research to examine the role of radon in breast cancer biology at the tissue level. We aim to understand molecular pathways linking radon exposure with breast cancer biology using transcriptome-wide-gene-expression from breast tumor and normal-adjacent tissues.MethodsOur study included 943 women diagnosed with breast cancer from the Nurses’ Health Study (NHS) and NHSII. We estimated cumulative radon concentration for each participant up-to the year of breast cancer diagnosis by linking residential addresses with a radon exposure model. Transcriptome-wide-gene-expression was measured with the Affymetrix-Glue-Human-Transcriptome-Array-3.0 and Human-Transcriptome-Array-2.0. We performed covariate-adjusted linear-regression for individual genes and further employed pathway-analysis. All analyses were conducted separately for tumor and normal-adjacent samples and by ER-status.ResultsNo individual gene was associated with cumulative radon exposure in ER-positive tumor, ER-negative tumor, or ER-negative normal-adjacent tissues at FDR < 5%. In ER-positive normal-adjacent samples, PLCH2—reached transcriptome-wide-significance (FDR < 5%). Gene-set-enrichment-analyses identified 2-upregulated pathways (MAPK signaling and phosphocholine biosynthesis) enriched at FDR < 25% in ER-negative tumors and normal-adjacent tissues, and both pathways have been previously reported to play key roles in ionizing radiation induced tumorigenesis in experimental settings.ConclusionOur findings provide insights into the molecular pathways of radon exposure that may influence breast cancer etiology.

Micronuclei frequency in peripheral blood lymphocytes and levels of anti-p53 autoantibodies in serum of residents of Kowary city regions (Poland) with elevated indoor concentrations of radon

IntroductionNinety four residents of Kowary city (Poland) have been investigated for environmental radon exposure that ranged from 0.24 WLM to 9.6 WLM (activity concentration range: 35–2700 Bq/m3). Kowary was chosen because of uranium mineralisation in its close vicinity. MethodWhole population studied was divided into two groups: exposed to low radon activity concentrations resulting in the exposure of ≤0.55 WLM (value corresponding to the exposure to 100 Bq/m3 during whole year), and exposed to high radon activity concentration (>0.55 WLM). In the two groups two selected biomarkers in blood were assessed: the cytokinesis-block micronucleus assay (CBMN) on peripheral blood lymphocytes (PBL), and the levels of anti-p53 antibodies in serum measured because some data indicate increased expression of the antibodies in individuals after exposure to DNA damaging agents including radon. The potential confounding factors known to influence micronuclei (MN) frequency were also measured in serum: vitamin B12, folic acid, as well as total calcium. ResultsIn the present study no significant correlation was found between MN frequency in PBL and radon exposure. Among all persons investigated only 11 had detectable levels of the anti-p53 antibodies, whereas only 3 persons had positive result. Therefore, the group was too small to perform any meaningful statistical analysis and to conclude on any association. Cigarette smoking did not significantly influence the number of MN. There was a significant positive correlation observed between MN frequency and age, as well as higher MN frequency was detected in women. ConclusionThe problem of the radon exposure is still unresolved and needs further studies on bigger human cohorts in order to search for more sensitive biomarkers.

Evaluation of correlation between PM2.5 and radon-progeny equilibrium factor in radon chamber

The dosage of environmental radon progeny is typically estimated according to the environmental radon exposure and the recommended radon-progeny equilibrium factor, F. To investigate the relationship between PM2.5 and the radon-progeny equilibrium factor, cigarettes are used to simulate the haze–fog in a multi-functional radon chamber to achieve a stable radon concentration environment. A radon detector and a portable laser aerosol spectrometer are used to obtain the values for Cmean PM2.5, CRn, and Cp. The results show that the mean values of F conform with the typical value recommended by the United Nations Scientific Committee on the Effects of Atomic Radiation and are within the reasonable range of 0.1–0.9. In this study, a positive correlation is observed between the F values and PM2.5 concentrations.

Environmental radon exposure and breast cancer risk in the Nurses\u2019 Health Study II

BackgroundRadon and its decay products, a source of ionizing radiation, are primarily inhaled and can deliver a radiation dose to breast tissue, where they may continue to decay and emit DNA damage-inducing particles. Few studies have examined the relationship between radon and breast cancer.MethodsThe Nurses’ Health Study II (NHSII) includes U.S. female registered nurses who completed biennial questionnaires since 1989. Self-reported breast cancer was confirmed from medical records. County-level radon exposures were linked with geocoded residential addresses updated throughout follow-up. Time-varying Cox regression models adjusted for established breast cancer risk factors were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsFrom 1989 to 2013, 3966 invasive breast cancer cases occurred among 112,639 participants. Increasing radon exposure was not associated with breast cancer risk overall (adjusted HR comparing highest to lowest quintile = 1.06, 95% CI: 0.94, 1.21, p for trend = 0.30). However, women in the highest quintile of exposure (≥74.9 Bq/m3) had a suggested elevated risk of ER−/PR- breast cancer compared to women in the lowest quintile (<27.0 Bq/m3) (adjusted HR = 1.38, 95% CI: 0.97, 1.96, p for trend = 0.05). No association was observed for ER+/PR+ breast cancer.ConclusionsAlthough we did not find an association between radon exposure and risk of overall or ER+/PR+ breast cancer, we observed a suggestive association with risk of ER−/PR- breast cancer.

Nonlinear dose-response relationship between radon exposure and the risk of lung cancer: evidence from a meta-analysis of published observational studies.

Although radon exposure (RE) has been confirmed to increase the risk of lung cancer (LC), questions remain about the shape of the dose-response relationship between RE and the risk of LC. We carried out a dose-response meta-analysis to investigate and quantify the potential dose-response association between residential and occupational exposure to radon and the risk of LC. All cohort and case-control studies published in English and Chinese on Embase, PubMed, and China National Knowledge Infrastructure (CNKI) digital databases through November 2013 were identified systematically. We extracted effect measures (relative risk, odds ratio, standardized mortality ratio, standardized incidence ratio, or standardized rate ratio) from individual studies to generate pooled results using meta-analysis approaches. We derived meta-analytic estimates using random-effects models taking into account the correlation between estimates. Restricted cubic splines and generalized least-squares regression methods were used to model a potential curvilinear relationship and to carry out a dose-response meta-analysis. Stratified analysis, sensitivity analysis, and assessment of bias were performed in our meta-analysis. Sixty publications fulfilling the inclusion criteria for this meta-analysis were finally included. Occupational RE was associated with LC [risk ratio 1.86, 95% confidence interval (CI)=1.67-2.09; I²=92.2%; 27 prospective studies], for pooled risk estimate of the: standardized mortality ratio [2.00 (95% CI=1.82-2.32)]; standardized incidence ratio [1.45 (95% CI=1.20-1.74)]; relative risk [2.10 (95% CI=1.64-2.69)]. In a subgroup analysis of uranium miners and residents exposed to occupational uranium, the summary risk was 2.23 (95% CI=1.86-2.68) and 1.23 (95% CI=1.05-1.44). The overall meta-analysis showed evidence of a nonlinear association between RE and the risk of LC (P(nonlinearity)<0.014); in addition, the point value of residential radon also improved the results quantitatively, where odds ratios were 1.11 (95% CI=1.07-1.15) and 1.21 (95% CI=1.14-1.29) when the radon concentration was at the point of 100 and 200 Bq/m³ compared with the lowest. For 17 prospective studies with at least three categories of occupational cumulative radon dose, the dose-risk model estimated a risk ratio of 1.26 (95% CI=1.21-1.30) for 100 working level months and 1.51 (95% CI=1.38-1.65) for 200 working level months, respectively. The assessment of risk of bias within individual studies and across studies indicated risk that was unlikely to alter these results markedly. This meta-analysis shows a nonlinear dose-response association between environmental RE and the risk of LC. This increased risk is particularly apparent when the cumulative exposure to radon is well beyond that resulting from exposure to the recommended limit concentration for a prolonged period of time.

Environmental Radon Exposure and Childhood Leukemia

Despite the fact that animal and human epidemiological studies confirmed a link between radon exposure in homes and increased risk of lung cancer in general population, other types of cancers induced by radon, such as leukemia, have not been consistently demonstrated. The aim of this review was to summarize data published thus far from ecological and case-control studies in exposed populations, taking into account radon dose estimation and evidence of radon-induced genotoxicity, in an effort to clarify the correlation between home radon exposure and incidence of childhood leukemia. Among 12 ecological studies, 11 reported a positive association between radon levels and elevated frequency of childhood leukemia, with 8 being significant. In conjunction with ecological studies, several case-control studies on indoor radon exposure and childhood leukemia were examined, and most investigations indicated a weak association with only a few showing significance. A major source of uncertainty in radon risk assessment is radon dose estimate. Methods for radon exposure measurement in homes of children are one of the factors that affect the risk estimates in a case-control study. The effects of radon-induced genetic damage were studied both in vitro and in vivo using genetic endpoints including chromosomal aberration (CA), micronuclei (MN) formation, gene mutation, and deletions and insertions. By applying a meta-analysis, an increased risk of childhood leukemia induced by indoor radon exposure was noted for overall leukemia and for acute lymphoblastic leukemia (ALL). Data thus indicated an association between environmental radon exposure and elevated leukemia incidence, but more evidence is required in both human investigations and animal mechanistic research before this assumption may be confirmed with certainty.

Radon and Skin Cancer in Southwest England

Radon, a naturally occurring radioactive gas, is a carcinogen that causes a small proportion of lung cancers among exposed populations. Theoretical models suggest that radon may also be a risk factor for skin cancer, but epidemiologic evidence for this relationship is weak. In this study, we investigated ecologic associations between environmental radon concentration and the incidence of various types of skin cancer. We analyzed data for 287 small areas (postcode sectors) in southwest England for the years 2000-2004. Poisson regression was used to compare registration rates of malignant melanoma, basal cell carcinoma, and squamous cell carcinoma across mean indoor radon concentrations from household surveys. Analyses were adjusted for potentially confounding factors, including age, sex, population socioeconomic status, and mean hours of bright sunshine. No association was observed between mean postcode sector radon concentration and either malignant melanoma or basal cell carcinoma registration rates. However, sectors with higher radon levels had higher squamous cell carcinoma registration rates, with evidence of an exposure-response relationship. Comparing highest and lowest radon categories, postcode sectors with mean radon ≥ 230 Bq/m(3) had registration rates 1.76 (95% confidence interval = 1.46-2.11) times those with mean radon 0-39 Bq/m(3). Associations persisted after adjustment for potential confounders. This ecologic study suggests that environmental radon exposure may be a risk factor for squamous cell carcinoma. Further study is warranted to overcome ecologic design limitations and to determine whether this relationship is generalizable to national and international settings.

Malignant transformation of human benign prostate epithelial cells by high linear energy transfer α-particles

Although epidemiological studies have suggested a positive correlation between environmental radon exposure and prostate cancer, the mechanism involved is not clear. In the present study, we examined the oncogenic transforming potency of alpha-particles using non-tumorigenic, telomerase-immortalized human benign prostate epithelial cells. We report the malignant transformation of human benign prostate epithelial cells after a single exposure to 0.6 Gy dose of alpha-particles. Transformed cells showed anchorage-independent growth in soft agar and induced progressively growing tumors when transplanted into SCID mice. The tumors were characterized histologically as poorly differentiated adenocarcinomas. The cell line derived from tumor (SCID 5015), like the unirradiated cells, expressed cytokeratin 5, 8 and 18, NKX3.1 and AMACR. The malignant cells showed increased secretion of MMP2. Stepwise chromosomal changes in the progression to tumorigenicity were observed. Chromosome abnormalities were identified in both irradiated and tumorigenic cells relative to the non-irradiated control cells. Prominent changes in chromosomes 6, 11 and 16, as well as mutations and deletions of the p53 gene were observed in the tumor outgrowth and tumor cells. These findings provide the first evidence of malignant transformation of human benign prostate epithelial cells exposed to a single dose of alpha-particles. This model provides an opportunity to study the cellular and molecular alterations that occur in radiation carcinogenesis in human prostate cells.

Health implications of radon distribution in living rooms and bedrooms in U.K. dwellings — A case study in Northamptonshire

Environmental radon exposure of residents of domestic premises in the United Kingdom (UK) and elsewhere in Europe is estimated on the basis of the measured radon concentrations in, and the relative occupancies of, the principal living room and bedroom. While studies on radon concentration variability in the individual units in apartment blocks in various countries have been described, little data has been reported on variability in two-storey single-family dwellings, and the majority of extant studies consolidate living room and bedroom data early in the analysis. To investigate this further, detailed analysis was made of radon concentration data from a set of thirty-four homes situated in areas of Northamptonshire known to exhibit high radon levels. All homes were of typical UK construction of brick/block/stone walls under a pitched tile/slate roof. Approximately 50% of the sample were detached houses, the remainder being semi-detached (duplex) or terraced (row-house). Around 25% of the sample possessed cellars, while 12% were single-storey dwellings (bungalows), reflecting the typical incidence of this type of dwelling in England. In the two-storey homes, all monitored bedrooms were on the upper floor.Distribution of the ratios of bedroom/living room radon concentrations (BR/LR ratio) in individual properties was left-skewed (mean 0.67, median 0.73, range 0.05–1.05) with a tail extending to just above 1.0. The mean is consistent with the outcome of earlier extensive studies in England, while the variability depends principally on the characteristics of the property, and not on seasonal factors. In a small set of homes, the BR/LR ratio was anomalously low, (mean 0.3). BR/LR ratios in single-storey homes clustered around a value of 1.0, indicating that house design, rather than lifestyle, is the dominant factor in determining bedroom radon concentrations. Homes with higher mean annual radon concentrations showed lower BR/LR ratios, supporting our proposal that, in some homes, radon emanation from building materials may comprise a significant component of the overall radon level.

Mutagenic effects of a single and an exact number of alpha particles in mammalian cells.

One of the main uncertainties in risk estimation for environmental radon exposure using lung cancer data from underground miners is the extrapolation from high- to low-dose exposure where multiple traversal is extremely rare. The biological effects of a single alpha particle are currently unknown. Using the recently available microbeam source at the Radiological Research Accelerator Facility at Columbia University, we examined the frequencies and molecular spectrum of S1- mutants induced in human-hamster hybrid (A(L)) cells by either a single or an exact number of alpha particles. Exponentially growing cells were stained briefly with a nontoxic concentration of Hoechst dye for image analysis, and the location of individual cells was computer-monitored. The nucleus of each cell was irradiated with either 1,2,4, or 8 alpha particles at a linear energy transfer of 90 keV/microm consistent with the energy spectrum of domestic radon exposure. Although single-particle traversal was only slightly cytotoxic to A(L) cells (survival fraction approximately 0.82), it was highly mutagenic, and the induced mutant fraction averaged 110 mutants per 10(5) survivors. In addition, both toxicity and mutant induction were dose-dependent. Multiplex PCR analysis of mutant DNA showed that the proportion of mutants with multilocus deletions increased with the number of particle traversals. These data provide direct evidence that a single a particle traversing a nucleus will have a high probability of resulting in a mutation and highlight the need for radiation protection at low doses.

The theoretical risk of non-melanoma skin cancer from environmental radon exposure

The skin cancer risk theoretically attributable to radon associated alpha particle radiation is calculated on the basis of recent dosimetry, and published radiation risk factors. The results suggest that of the order of 2% (range 1%-10%) of non-melanoma skin cancers in the UK may be associated with radon exposure at the average UK radon concentration of 20 Bq m-3. The range quoted is due solely to uncertainties in the estimate of the radon dose to the basal layer of the skin, and additional sources of uncertainty are discussed. The estimate is dependent on the assumption that the target cells for radiation induced skin cancer lie in the basal layer of the epidermis, and that irradiation of the dermis is not necessary for skin cancer induction. Due to the effect of ultraviolet radiation on the risk factors for ionising radiation, ultraviolet radiation exposure must also be involved in the induction of the majority of any skin cancer cases linked to radon exposure.

Radon, Cigarette Smoke, and Lung Cancer

Much of our knowledge regarding the interaction of radon and tobacco smoke in the etiology of human lung cancer derives from studies of uranium miners. In this article, we present a re-analysis of lung cancer mortality in the Colorado Plateau miners' cohort within the framework of the two-mutation clonal expansion model of carcinogenesis. This analysis takes into account the patterns of exposure to radon and cigarette smoke experienced by individuals in the cohort. A simultaneous re-analysis of the British doctors' cohort indicated that those model parameters relating to the effects of tobacco were comparable in the two data sets. We found no evidence of interaction between radon and tobacco smoke with respect to their joint effect on the first or second stage mutation rates or on the rate of proliferation of initiated cells. The age-specific relative risks associated with joint exposure to radon and cigarette smoke, however, were supra-additive but submultiplicative. The analysis also confirmed that fractionation of radon exposures leads to higher lung cancer risks. Finally, we present some estimates of lung cancer risk from environmental radon exposure for non-smokers and smokers.