Lung cancer risk and residential radon exposure: A pooling of case-control studies in northwestern Spain.

BACKGROUND: Through a pooled case-control study design, we have assessed the relationship between residential radon exposure and lung cancer risk. Other objectives of the study were to evaluate the different risk estimates for the non-small cell lung cancer histological types and to assess the effect modification of the radon exposure on lung cancer risk by tobacco consumption. METHODS: We collected individual data from various case-control studies performed in northwest Spain that investigated residential radon and lung cancer. Cases had a confirmed anatomopathological diagnosis of primary lung cancer and controls were selected because they were undergoing ambulatory evaluation or surgical procedures that were unrelated to tobacco use. Residential radon was measured using alpha track detectors. Results were analyzed using logistic regression. RESULTS: 3704 participants were enrrolled, 1842 cases and 1862 controls. Data show that lung cancer risk increases with radon exposure, finding a significant association of radon exposure with lung cancer at radon exposures above 50 Bq/m3. The estimated adjusted OR for individuals exposed to concentrations >200 Bq/m3 was 2.06 (95% CI: 1.61-2.64) compared with those exposed to ≤50 Bq/m3. Within a smoking category, lung cancer risk increases markedly as radon concentration increases, reaching an OR of 29.3 (95% CI: 15.4-55.7) for heavy smokers exposed to more than 200 Bq/m.3 CONCLUSIONS: This study confirms that residential radon exposure is a risk factor for lung cancer well below action levels established by international organizations. As expected, there is also an effect modification between radon exposure and tobacco consumption.

Lung cancer and residential radon in never-smokers: A pooling study in the Northwest of Spain.

BACKGROUND: Using a pooled case-control study design, including only never-smokers, we have assessed the association of residential radon exposure with the subsequent occurrence of lung cancer. We also investigated whether residential radon poses a different risk specifically for adenocarcinoma. METHODS: We pooled individual data from different case-control studies conducted in recent years in Northwestern Spain which investigated residential radon and lung cancer. All participants were never-smokers. Cases had a confirmed biopsy of primary lung cancer. Hospital controls were selected at pre-surgery units, presenting for non-complex surgical procedures. They were interviewed using a standardized instrument. Residential radon was measured using alpha track detectors at the Galician Radon Laboratory at the University of Santiago de Compostela. RESULTS: A total of 1415 individuals, 523 cases and 892 controls were included. We observed an odds ratio of 1.73 (95%CI: 1.27-2.35) for individuals exposed to ≥ 200 Bq/m3 compared with those exposed to ≤100 Bq/m3. Lung cancer risk for adenocarcinoma was 1.52 (95%CI: 1.14-2.02) using the same categories for radon exposure. CONCLUSIONS: Residential radon is a clear risk factor for lung cancer in never-smokers. Our data suggest that radon exposure is associated with all histological types of lung cancer and also with adenocarcinoma, which is currently the most frequent histological type for this disease.

Alcohol consumption and lung cancer risk in never smokers: a pooled analysis of case-control studies.

Background: Lung cancer is the deadliest cancer in developed countries but the etiology of lung cancer risk in never smokers (LCRINS) is largely unknown. We aim to assess the effects of alcohol consumption, in its different forms, on LCRINS. Methods: We pooled six multi-center case-control studies developed in the northwest of Spain. Cases and controls groups were composed of never smokers. We selected incident cases with anatomopathologically confirmed lung cancer diagnoses. All participants were personally interviewed. We performed two groups of statistical models, applying unconditional logistic regression with generalized additive models. One considered the effect of alcohol type consumption and the other considered the quantity of each alcoholic beverage consumed. Results: A total of 438 cases and 863 controls were included. Median age was 71 and 66, years, respectively. Adenocarcinoma was the predominant histological type, comprising 66% of all cases. We found that any type of wine consumption posed an OR of 2.20 OR 95%CI 1.12-4.35), and spirits consumption had an OR of 1.90 (95%CI 1.13-3.23). Beer consumption had an OR of 1.33 (95%CI 0.82-2.14). These results were similar when women were analyzed separately, but for men there was no apparent risk for any alcoholic beverage. The dose-response analysis for each alcoholic beverage revealed no clear pattern. Conclusions: Wine and spirits consumption might increase the risk of LCRINSs, particularly in females. These results have to be taken with caution given the limitations of the present study.

Alcohol and lung cancer risk among never smokers: A pooled analysis from the international lung cancer consortium and the SYNERGY study.

It is not clear whether alcohol consumption is associated with lung cancer risk. The relationship is likely confounded by smoking, complicating the interpretation of previous studies. We examined the association of alcohol consumption and lung cancer risk in a large pooled international sample, minimizing potential confounding of tobacco consumption by restricting analyses to never smokers. Our study included 22 case-control and cohort studies with a total of 2548 never-smoking lung cancer patients and 9362 never-smoking controls from North America, Europe and Asia within the International Lung Cancer Consortium (ILCCO) and SYNERGY Consortium. Alcohol consumption was categorized into amounts consumed (grams per day) and also modelled as a continuous variable using restricted cubic splines for potential non-linearity. Analyses by histologic sub-type were included. Associations by type of alcohol consumed (wine, beer and liquor) were also investigated. Alcohol consumption was inversely associated with lung cancer risk with evidence most strongly supporting lower risk for light and moderate drinkers relative to non-drinkers (>0-4.9 g per day: OR = 0.80, 95% CI = 0.70-0.90; 5-9.9 g per day: OR = 0.82, 95% CI = 0.69-0.99; 10-19.9 g per day: OR = 0.79, 95% CI = 0.65-0.96). Inverse associations were found for consumption of wine and liquor, but not beer. The results indicate that alcohol consumption is inversely associated with lung cancer risk, particularly among subjects with low to moderate consumption levels, and among wine and liquor drinkers, but not beer drinkers. Although our results should have no relevant bias from the confounding effect of smoking we cannot preclude that confounding by other factors contributed to the observed associations. Confounding in relation to the non-drinker reference category may be of particular importance.

Radon, Tobacco Exposure and Non-Small Cell Lung Cancer Risk Related to BER and NER Genetic Polymorphisms.

INTRODUCTION: Tobacco consumption and radon exposure are considered the first and second most common causes of lung cancer, respectively. The aim of this study was to analyze both whether selected genetic polymorphisms in loci that are in DNA repair pathways, are related to non-small-cell lung cancer (NSCLC) and whether they may modulate the association between residential radon exposure and lung cancer in both smokers and never smokers. METHODS: A multicentre, hospital-based, case-control study with 826 cases and 1201 controls was designed in a radon-prone area. Genotyping was determined in whole blood and residential radon exposure was measured in participants' dwellings. RESULTS: Attending to tobacco exposure, the variant in the gene NBN (rs1805794) was associated with lung cancer in never smokers (OR 2.72; 95%1.44-5.2) and heavy smokers (OR 3.04; 95%CI 1.21-7.69). The polymorphism with the highest lung cancer association was OGG1 (rs125701), showing an OR of 8.04 (95%CI 1.64-58.29) for its homozygous variant genotype in heavy smokers. Attending to indoor radon exposure (>200Bq/m3), rs1452584, for its homozygous variant genotype, showed the highest association (OR 3.04 (95%CI 1.15-8.48). CONCLUSION: The genes analyzed seem to have no association with the fully adjusted model, but they might modulate lung cancer association when different categories of tobacco consumption are considered (i.e. heavy smokers). This association may similarly be elevated for those individuals having high indoor radon exposures, though at a minor extent.

[Radon exposure and genitourinary cancer in miners]. / Exposición al radón y cáncer genitourinario en mineros.

OBJECTIVE: To assess the association between exposure to radon and genitourinary cancer in a mining population through a systematic review of the scientific literature. METHOD: A systematic review of the scientific literature was carried out in MEDLINE (PubMed), combining MeSH (Medical Subject Heading) terms and free terms. We applied a specific scale to assess the quality of the included studies. RESULTS: We included 17 studies; all were cohort studies with the exception of one which was a pooling of data. All studies included analysed the relationship between exposure to radon and genitourinary cancer. While some studies point towards an association between radon exposure and genitourinary cancer, especially kidney cancer, others do not find such association. CONCLUSIONS: The included studies showed great heterogeneity. It cannot be concluded that there is an association between exposure to radon and genitourinary cancer. More research is needed on this topic, designing studies with higher statistical power, better control of confounders, and preferably prospective.

Attributable mortality to radon exposure in Galicia, Spain. Is it necessary to act in the face of this health problem?

BACKGROUND: Radon is the second risk factor for lung cancer after tobacco consumption and therefore it is necessary to know the burden of disease due to its exposure. The objective of this study is to estimate radon-attributable lung cancer mortality in Galicia, a high emission area located at the Northwest Spain. METHODS: A prevalence-based attribution method was applied. Prevalence of tobacco use and radon exposure were obtained from a previously published study of the same area. Attributable mortality was calculated for each of six possible risk categories, based on radon exposure and smoking status. Two scenarios were used, with 37 Bq/m3 and 148 Bq/m3 as the respective radon exposure thresholds. As the observed mortality we used lung cancer mortality for 2001 from the Galician mortality registry. RESULTS: Mortality exclusively attributable to radon exposure ranged from 3% to 5% for both exposure thresholds, respectively. Attributable mortality to combined exposure to radon and smoking stood at around 22% for exposures above 148 Bq/m3. Applying the United States Environmental Protection Agency (EPA) action level, radon has a role in 25% of all lung cancers. CONCLUSIONS: Although the estimates have been derived from a study with a relatively limited sample size, these results highlight the importance of radon exposure as a cause of lung cancer and its effect in terms of disease burden. Radon mitigation activities in the study area must therefore be enforced.

Residential Radon in Central and South America: A Systematic Review.

Radon gas is a pulmonary carcinogen and the second leading cause of lung cancer after smoking. There are many countries that have not implemented measures to reduce the risk it poses to the general population. The aim of this study was to locate available evidence on exposure to residential radon and the regulations to monitor and control this across Central and South America, by conducting a review of the scientific literature and government documents in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This review included 31 studies which had taken measurements of radon in these countries. While Brazil, Argentina, and Peru have undertaken most research, no country in Central and South America has a national map of exposure to residential radon. The prevalence of exposure to radon was uneven, both among the different countries and within individual countries. No country has regulations to prevent the entry of radon into homes, and nine countries have not set maximum permissible concentrations for residential radon. There is a limited number of studies in South and Central America, with a limited spatial coverage, and there is a need to improve knowledge on exposure to residential radon and its effects, and for governments to take the necessary actions to introduce preventive measures in their statutory regulations.

Is there a specific mutation of p53 gene due to radon exposure? A systematic review.

PURPOSE: To review the existing literature analysing the influence of radon exposure on mutations in tumour protein 53 gene (TP53) in lung cancer patients. MATERIAL AND METHODS: Medline and EMBASE databases along with the International Agency for Research on Cancer (IARC) monographies were revised. Studies that had radon concentration as exposure variable and TP53 mutations as a result variable were included. RESULTS: Eight studies were obtained, with a total of 578 individuals. They had been carried out on miners and on general population. A 26% of the miners' tumours had a mutation in gene TP53, versus a 24% in the population exposed to residential radon. A predominance of the AGG(ARG)--> ATG(MET) (Arginine to Methionine) mutation in miners was observed. CONCLUSIONS: The available results are not consistent in order to support the existence of a radon hotspot in TP53 gene. Future research should focus at least on exons 5 to 8, where most of the mutation clusters in lung tumours are observed.

Residential radon, genetic polymorphisms in DNA damage and repair-related.

OBJECTIVES: To analyze the relationship of GSTT1, GSTM1, XRCC1 (rs25487), ERCC1 (rs11615, rs3212986), ERCC2 (rs13181), XRCC3 (rs861539), OGG1 (rs1052133), and Alpha-1-Antitrypsin mutations (AAT) with the risk of lung cancer in never-smokers, and ascertain if there is an effect modification between these polymorphisms and residential radon exposure. MATERIAL AND METHODS: We designed a multicenter hospital-based case-control study in a radon-prone area. 322 cases and 338 controls, all never-smokers, were included. They were selected using a frequency sampling based on sex and age distribution of the cases. Participants donated 3 ml. of whole blood used to determine genotype for polymorphisms. They placed a radon detector to measure residential radon exposure in their dwelling. RESULTS: The OR for deleted GSTM1 patients was 3.46 (95% CI = 1.52-7.89) at residential radon exposures above 200 Bq/m3. The ERCC1 rs3212986 polymorphism was the most associated with the risk of developing lung cancer, both for low and high radon exposures. The ERCC1 rs321986 GT and TT genotypes (at radon concentrations >200 Bq/m3) were more significantly associated with higher lung cancer risk (OR = 2.40, 95% CI = 1.29-4.45; OR = 4.45, 95% CI = 1.26-15.7, respectively). CONCLUSIONS: These findings support the hypothesis that certain polymorphisms in genes involved in DNA-repair and carriers of GSTM1 deletion have an increased risk of lung cancer in never-smokers exposed to residential radon.

Alcohol consumption and lung cancer risk: A pooled analysis from the International Lung Cancer Consortium and the SYNERGY study.

BACKGROUND: There is inadequate evidence to determine whether there is an effect of alcohol consumption on lung cancer risk. We conducted a pooled analysis of data from the International Lung Cancer Consortium and the SYNERGY study to investigate this possible association by type of beverage with adjustment for other potential confounders. METHODS: Twenty one case-control studies and one cohort study with alcohol-intake data obtained from questionnaires were included in this pooled analysis (19,149 cases and 362,340 controls). Adjusted odds ratios (OR) or hazard ratios (HR) with corresponding 95% confidence intervals (CI) were estimated for each measure of alcohol consumption. Effect estimates were combined using random or fixed-effects models where appropriate. Associations were examined for overall lung cancer and by histological type. RESULTS: We observed an inverse association between overall risk of lung cancer and consumption of alcoholic beverages compared to non-drinkers, but the association was not monotonic. The lowest risk was observed for persons who consumed 10-19.9 g/day ethanol (OR vs. non-drinkers = 0.78; 95% CI: 0.67, 0.91), where 1 drink is approximately 12-15 g. This J-shaped association was most prominent for squamous cell carcinoma (SCC). The association with all lung cancer varied little by type of alcoholic beverage, but there were notable differences for SCC. We observed an association with beer intake (OR for ≥20 g/day vs nondrinker = 1.42; 95% CI: 1.06, 1.90). CONCLUSIONS: Whether the non-monotonic associations we observed or the positive association between beer drinking and squamous cell carcinoma reflect real effects await future analyses and insights about possible biological mechanisms.

Meta-analysis and pooled analysis of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancers: a HuGE-GSEC review.

The association of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancers was assessed through a meta-analysis of published case-control studies and a pooled analysis of both published and unpublished case-control studies from the Genetic Susceptibility to Environmental Carcinogens database (http://www.upci.upmc.edu/research/ccps/ccontrol/index.html ). Thirty publications used in the meta-analysis included a total of 7783 subjects (3177 cases and 4606 controls); 21 datasets, 9397 subjects (3130 cases and 6267 controls) were included in the pooled analysis. The GSTM1 deletion was 2-fold more likely to occur in African American and African cases than controls (odds ratio: 1.7, 95% confidence interval: 0.9-3.3), although this was not observed among whites (odds ratio: 1.0, 95% confidence interval: 0.9-1.1). The meta-analysis and pooled analysis showed a significant association between oral and pharyngeal cancer and the CYP1A1 MspI homozygous variant (meta-ORm2/m2: 1.9, 95% confidence interval: 1.4-2.7; Pooled ORm2m2: 2.0, 95% confidence interval: 1.3-3.1; ORm1m2 or [infi]m2m2: 1.3, 95% confidence interval: 1.1-1.6). The association was present for the CYP1A1 (exon 7) polymorphism (ORVal/Val: 2.2, 95% confidence interval: 1.1-4.5) in ever smokers. A joint effect was observed for GSTM1 homozygous deletion and the CYP1A1 m1m2 variant on cancer risk. Our findings suggest that tobacco use and genetic factors play a significant role in oral and pharyngeal cancer.

Consumption of fruit and vegetables and risk of lung cancer: a case-control study in Galicia, Spain.

OBJECTIVE: We analyzed the effect of fruit and vegetable intake on lung cancer risk in a population in northwest Spain. METHODS: We analyzed data from a hospital-based case-control study including 295 histologically confirmed cases and 322 controls. Controls were patients attending the hospital for minor surgery. There was a minimum age limit of 35 y and sampling was carried out on a sex-frequency basis. RESULTS: After adjustment for sex, age, tobacco use, and occupation, no protective effect of overall consumption of fruit was present (odds ratio 1.49, 95% confidence interval 0.81-2.73). Green leafy vegetables conferred a protective effect (odds ratio 0.50, 95% confidence interval 0.30-0.83). CONCLUSION: These findings indicate that green leafy vegetables, rather than fruit, might have a genuine protective effect against lung cancer.

Residential radon and small cell lung cancer. A systematic review.

Residential radon exposure is considered the second cause of lung cancer and the first in never smokers. Nevertheless, the association between the different histological types of lung cancer and radon is not completely clear, and radon effect on small cell lung cancer is not completely understood. We aim to asses the effect of residential radon exposure on the risk of small cell lung cancer (SCLC) in general population and miners through a systematic review applying predefined inclusion and exclusion criteria. 16 studies were included. Most of them point to a relationship between indoor radon and SCLC, though some investigations show no association. When comparing the risk of SCLC due to radon exposure with NSCLC, it can be observed that an increased risk for SCLC is present. Small cell lung cancer seems to be the histological type of lung cancer most tightly related with residential radon.

Residential radon and cancer mortality in Galicia, Spain.

Residential radon exposure is a serious public health concern, and as such appears in the recommendations of European Code Against Cancer. The objective of this study was to assess the association between residential radon levels and mortality due to different types of cancer, using misaligned data analysis techniques. Mortality data (observed cases) for each of the 313 Galician municipalities were drawn from the records of the National Statistics Institute for the study period (1999-2008). Expected cases were computed using Galician mortality rates for 14 types of malignant tumors as reference, with a total of 56,385 deaths due to the tumors analyzed. The effect estimates of indoor radon (3371 sampling points) were adjusted for sociodemographic variables, altitude, and arsenic topsoil levels (1069 sampling points), using spatial/geostatistical models fitted with stochastic partial differential equations and integrated nested Laplace approximations. These models are capable of processing misaligned data. The results showed a statistical association between indoor radon and lung, stomach and brain cancer in women in Galicia. Apart from lung cancer (relative risk (RR)=1.09), in which a twofold increase in radon exposure led to a 9% rise in mortality, the association was particularly relevant in stomach (RR=1.17) and brain cancer (RR=1.28). Further analytical epidemiologic studies are needed to confirm these results, and an assessment should be made of the advisability of implementing interventions targeting such exposure in higher-risk areas.

Residential radon and lung cancer: a cohort study in Galicia, Spain.

Case-control studies show an association between residential radon and lung cancer. The aim of this paper is to investigate this association through a cohort study. We designed an ambispective cohort study using the Galician radon map, Spain, with controls drawn from a previous case-control study. Subjects were recruited between 2002 and 2009. The data were cross-checked to ascertain lung cancer incidence and then analysed using a Cox regression model. A total of 2,127 subjects participated; 24 lung cancer cases were identified; 76.6% of subjects were drawn from the radon map. The adjusted hazard ratio was 1.2 (95%CI: 0.5-2.8) for the category of subjects exposed to 50Bq/m3 or more. This risk rose when subjects from the case-control study were analyzed separately. In conclusion, we did not observe any statistically significant association between residential radon exposure and lung cancer; however, it appears that with a sample of greater median age (such as participants from the case-control study), the risk of lung cancer would have been higher.

Residential radon exposure and brain cancer: an ecological study in a radon prone area (Galicia, Spain).

We aimed to know if radon concentration is associated with municipal mortality due to brain cancer in Galicia, Spain. We designed an ecological study taking as study unit Galician municipalities. To be included, municipalities had to have at least three radon measurements. We correlated radon concentrations with municipal mortality due to these malignant tumors during the period 1999-2008. We calculated the relative risk of dying of brain cancers for each municipality and correlated this value with municipal radon concentration using Spearman's Rho. 251 municipalities were included, with close to 3,500 radon measurements and an average of 14 radon measurements at each municipality. We observed a significant correlation between residential radon with brain cancer mortality for males and females and the intensity of the correlation was higher for females. These results were reinforced when the analysis was restricted to municipalities with more than 5 radon measurements: Spearman's Rho 0.286 (p-value < 0.001) and Spearman's Rho 0.509 (p-value < 0.001) for males and females, respectively. These results suggest an association between residential radon and brain cancer mortality. More research using more robust epidemiological designs is needed to confirm these findings.

Residential radon and COPD. An ecological study in Galicia, Spain.

PURPOSE: Radon is a human lung carcinogen but it might be linked with other respiratory diseases. We aimed to assess the relationship between residential radon exposure and COPD (chronic obstructive pulmonary disease) prevalence and hospital admissions at a municipal level. MATERIALS AND METHODS: We designed an ecological study where we included those municipalities with at least three radon measurements. Using mixed Poisson regression models, we calculated the relative risk (RR) for COPD for each 100 Bq/m3 of increase in radon concentration and also the relative risk for COPD using a cut-off point of 50 Bq/m3. We did not have individual data on cigarette smoking and therefore we used a proxy (bladder cancer standardized mortality rate) that has proved to account for tobacco consumption. We performed separate analyses for sex and also sensitivity analysis considering age and rurality. RESULTS: A total of 3040 radon measurements and 49,393 COPD cases were included. The relative risk for COPD prevalence was 0.95 (95% CI: 0.92-0.97) while for hospital admissions the RR was 1.04 (95% CI: 1.00-1.10) for each 100 Bq/m3. Relative risks were higher for women compared to men. Using a categorical analysis with a cut-off point of 50 Bq/m3, the RR for COPD prevalence was 1.06 (95% CI: 1.02-1.10) and for hospital admissions it was 1.08 (95% CI: 1.00-1.17) for women living in municipalities with more than 50 Bq/m3. All risks were also higher for women. No relevant differences were observed for age, rurality or other categories for radon exposure. CONCLUSION: While the influence of radon on COPD prevalence is unclear depending on the approach used, it seems that residential radon might increase the risk of hospital admissions in COPD patients. Women have a higher risk than men in all situations. Since this is an ecological study, results should be interpreted cautiously.