Radon exposure and its influencing factors across 3,140 workplaces in Spain.

Indoor radon exposure increases the risk of lung cancer. Radon concentration in workplaces is regulated in EU countries, including Spain, based on a reference level of 300 Bq/m3. The objective of this study is to describe workplace radon exposure in Spain and its influencing factors. To do this, we collected long-term radon measurements with alpha track detectors in 3140 workplaces mainly located in radon prone areas. Radon concentration exceeded 300 Bq/m3 in 1 out of 5 workplaces. Median radon concentration was 107 Bq/m3 in radon prone areas, 28 Bq/m3 off radon prone areas, and 101 Bq/m3 globally for the complete sample. Our results indicate that excessive radon concentrations can be expected in radon prone areas at all floor levels, especially below ground. Floor level, working sector, and location significantly influence radon concentration. The highest radon concentrations were found in the Education & Culture sector, comprising schools, universities, libraries, or cultural centers. These results indicate that radon should no longer be considered a risk for marginal occupations, but a risk everyone has if located in a radon prone area. Immediate action, including radon testing and mitigation, is needed to protect workers in Spain against radon exposure. This is already mandatory since EU regulation for radon has been recently transposed in Spain. Competent authorities should enforce this regulation without further delay, and employers must address their responsibility and communicate with workers about this risk.

Alpha-1 antitrypsin deficiency and risk of lung cancer in never-smokers: a multicentre case-control study.

BACKGROUND: Lung cancer (LC) is the most commonly diagnosed cancer and the leading cause of cancer-related death in both sexes worldwide. Although the principal risk factor in the western world is tobacco smoking, genetic factors, including alpha-1 antitrypsin deficiency (AATD), have been associated with increased risk. This study is the continuation of an earlier one published by the same group in 2015, aimed at analysing risk of LC in never-smokers, associated with carriers of the AATD genotype. METHODS: A multicentre case-control study was conducted in Spain across the period January 2011 to August 2019. Cases were non-smokers diagnosed with LC, and controls were composed of never-smoking individuals undergoing major non-cancer-related surgery. Data were collected on epidemiological characteristics, exposure to environmental tobacco smoke (ETS), residential radon levels, and alpha-1 antitrypsin (AAT) genotype. RESULTS: The study included 457 cases (42%) and 631 controls (58%), with a predominance of women (72,8%). The most frequent histological type was adenocarcinoma (77.5%), followed by squamous cell carcinoma (7.7%). No association of risk of LC was found with the status of AATD genotype carrier, both overall and broken down by age, sex, or exposure to ETS. CONCLUSIONS: No risk association was found between being a carrier of an AAT deficiency genotype and LC among never-smokers. In order to establish the existence of an association, we consider it important to expand the studies in never smokers in different geographical areas as well as to include patients with previous chronic lung diseases to assess if it influences the risk.

Fruits and Vegetables and Lung Cancer Risk in Never Smokers. A Multicentric and Pooled Case-Control Study.

BACKGROUND: The etiology of lung cancer in never smokers is partly unknown. We aimed to assess the effect of fruits and vegetables consumption on lung cancer risk in never smokers. METHODS: We pooled five multicenter case-control studies performed in Northwestern Spain. Cases and controls were all never smokers. All lung cancer cases had anatomopathological confirmed diagnoses. We performed a multivariate logistic regression to analyze the effect of different types of fruits and vegetables consumption on lung cancer risk. RESULTS: A total of 438 cases and 781 controls were included. We observed that a consumption from one to six times per week shows a negative association with lung cancer risk for: kiwis (OR 0.67; 95%CI 0.46-0.95), oranges (OR 0.55; 95%CI 0.37-0.80), turnip tops (OR 0.48; 95%CI 0.34-0.66), "berza gallega" (OR 0.70; 95%CI 0.51-0.97) and broccoli (OR 0.55; 95%CI 0.35-0.83) compared to less than once a week consumption. On the other hand, we found an increased risk for lung cancer with a daily consumption of tomatoes, carrots and potatoes. CONCLUSIONS: Oranges, kiwis, turnip tops, berza gallega and broccoli may play a protective role on lung cancer development in never smokers while tomatoes, carrots and potatoes might have some association with this disease.

Radon exposure and inflammatory bowel disease in a radon prone area.

INTRODUCTION: inflammatory bowel disease (IBD) is a multifactorial pathology with an increasing incidence. There is no study that has assessed a possible relationship with very high residential radon exposure in the study area. The aim of the study was to analyze if residential radon concentration is associated with a higher incidence of IBD. MATERIAL AND METHODS: an ecological study was performed. All incident cases of inflammatory bowel disease in the area of Santiago de Compostela were included between January and December 2017. Radon levels at a municipal level were correlated with demographic factors and type of IBD. RESULTS: ninety-six patients were included, 63 (65.6 %) with ulcerative colitis, 29 (30.25) with Crohn's disease and four (4.2 %) with indeterminate colitis. The incidence rate per 100,000 inhabitants-year was 21.6 cases. There were no statistically significant differences in the type of disease developed regarding radon levels (p > 0.05). No correlation between radon levels and the cumulative incidence of inflammatory bowel disease at the municipal level was observed (Spearman's rho = 0.13, p-value 0.5). CONCLUSION: in the area of Santiago de Compostela, there is a higher incidence of IBD in comparison with previous studies using western countries as reference. However, there was no correlation with the municipal average radon concentration and incidence of IBD or any of its types in this study.

Lung cancer mortality attributable to residential radon exposure in Spain and its regions.

Lung cancer has the highest cancer mortality rate in developed countries. The principal risk factor for lung cancer is tobacco use, with residential radon being the leading risk factor among never smokers and the second among ever smokers. We sought to estimate mortality attributable to residential radon exposure in Spain and its Autonomous Regions, with correction for dwelling height and differentiation by tobacco use. We applied a prevalence-based method for estimating attributable mortality. For estimations, we considered exposure to radon in the different Autonomous Regions corrected for dwelling height, using the National Statistics Institute Housing Census and prevalence of tobacco use (never smokers, smokers and ex-smokers). The results showed that 3.8% (838 deaths) of lung cancer mortality was attributable to radon exposure of over 100 Bq/m3, a figure that rises to 6.9% (1,533 deaths) when correction for dwelling height is not performed. By Autonomous Region, the highest population attributable fractions, corrected for dwelling height, were obtained for Galicia, Extremadura, and the Canary Islands, where 7.0, 6.9, and 5.5% of lung cancer mortality was respectively attributable to radon exposure. The greatest part of the attributable mortality occurred in men and among smokers and ex-smokers. Residential radon exposure is a major contributor to lung cancer mortality, though this contribution is highly variable among the different territories, indicating the need for targeted prevention policies. Correction of estimates for dwelling height is fundamental for providing reliable estimates of radon-attributable mortality.

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.

Lung cancer risk and do-it-yourself activities. A neglected risk factor for lung cancer.

BACKGROUND: The aim of this study was to assess the relationship between do-it-yourself activities entailing the exposure to carcinogenic substances and the risk of lung cancer. METHODS: We pooled individual data from different case-control studies conducted in Northwestern Spain which investigated residential radon and lung cancer. Cases had an anatomopathologically confirmed primary lung cancer and controls were selected at the pre-surgery unit with uncomplicated surgeries. Both cases and controls were older than 30 years with no previous cancer history. All participants were interviewed face-to-face using a specific questionnaire. Painting, model building, furniture refinishing and woodworking or home carpentry were the do-it-yourself activities considered risky due to exposure to carcinogenic agents. RESULTS: We included 1528 cases and 1457 controls. Practicing do-it-yourself risk activities was more frequent among cases: 16.0% were exposed to carcinogenic exposures during leisure time, compared to 11.8% for controls. The overall adjusted OR for lung cancer risk among individuals who practiced do-it-yourself risk activities, was 1.77 (95% CI: 1.36-2.31); this was 2.17 (95% CI: 1.51-3.11) when the analysis was restricted to individuals who performed these activities for at least 10 years. These risks were greater when the analyses were carried out exclusively among never-smokers, with the respective ORs being 2.04 (95% CI: 1.38-3.01) and 3.10 (95% CI: 1.78-5.40). CONCLUSION: These results support the hypothesis that do-it-yourself activities involving exposure to certain carcinogens are associated with an increased risk of lung cancer, both in ever and never-smokers.

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.

Residential radon in Galicia: a cross-sectional study in a radon-prone area.

Residential radon exposure is a major public health problem. It is the second greatest cause of lung cancer, after smoking, and the greatest in never-smokers. This study shows the indoor radon exposure distribution in Galicia and estimates the percentage of dwellings exceeding reference levels. It is based on 3245 residential radon measurements obtained from the Galician Radon Map project and from controls of two previous case-control studies on residential radon and lung cancer. Results show a high median residential radon concentration in Galicia (99 Bq m-3), with 49.3% of dwellings having a radon concentration above 100 Bq m-3 and 11.1% having a concentration above 300 Bq m-3. Ourense and Pontevedra, located in South Galicia, are the provinces with the highest median indoor radon concentrations (137 Bq m-3 and 123.5 Bq m-3, respectively). Results also show lower radon levels in progressively higher building storeys. These high residential radon concentrations confirm Galicia as a radon-prone area. A policy on radon should be developed and implemented in Galicia to minimize the residential radon exposure of the population.

Residential radon, EGFR mutations and ALK alterations in never-smoking lung cancer cases.

The aim of this study was to assess if residential radon exposure might cause EGFR mutations or ALK rearrangements in never-smokers.We designed a multicentre case-control study in a radon-prone area (Galicia, Spain); only lung cancer cases were included in the study. We obtained residential radon measurements and clinical information for all the participants. We compared the median values of residential radon between patients with EGFR mutations or ALK rearrangements versus those without them.323 patients were included. Median age was 70 years and 19.5% were males. 42 and 15% of patients were EGFR- and ALK-positive, respectively. The most frequent EGFR alterations were exon 19 deletions and exon 21 (L858R) single-point substitution mutations. ALK-positive patients were 10 years younger than ALK-negative patients. Residential radon levels were two-fold higher in patients with exon 19 deletions compared with patients with exon 21 (L858R) single-point substitution mutations (216 versus 118 Bq·m-3; p=0.057). There were no differences in residential radon levels by EGFR mutation status. ALK-positive patients (n=12) essentially had two-fold residential radon levels compared with ALK-negative patients (290 versus 164 Bq·m-3, respectively).Residential radon may have a role in the molecular signature of lung cancer in never-smokers, although more studies with larger sample sizes are needed to support this hypothesis.

Small cell lung cancer in never-smokers.

Our aim was to describe the characteristics of a case-series of never-smoker small cell lung cancer (SCLC) cases.Cases of SCLC were selected from a prospective, multicenter, hospital-based case-control study performed in Spain. Participants were never-smokers older than 30 years with an anatomo-pathological confirmation of primary lung cancer. We collected clinical and epidemiological variables according to the study's protocol.We included 19 SCLC cases, 18 females (94.7%), median age 75 years (interquartile range (IQR) 70-80 years). Median residential radon concentration was 195 Bq·m(-3) (IQR 130-229 Bq·m(-3)). 10 patients had limited disease and nine had extended disease. Median survival was 242 days (IQR 94-496 days); 1- and 2-year survival were 36.8% and 17.6%, respectively. Survival was much higher for individuals with limited disease than for those with extended disease (median 336 versus 235 days; 1-year survival 50% versus 22.2% and 2-year survival 27% versus 0%, respectively). Performance status at diagnosis was closely related to survival.SCLC is an infrequent, highly aggressive disease in never-smokers. Survival is poor, even for limited disease. Age at diagnosis in SCLC is higher than that observed for never-smokers with adenocarcinoma. Residential radon exposure is higher than the action levels recommended by the World Health Organization.

Lung cancer in never-smokers: a case-control study in a radon-prone area (Galicia, Spain).

The aim of the study was to assess the effect of residential radon exposure on the risk of lung cancer in never-smokers and to ascertain if environmental tobacco smoke modifies the effect of residential radon. We designed a multicentre hospital-based case-control study in a radon-prone area (Galicia, Spain). All participants were never-smokers. Cases had an anatomopathologically confirmed primary lung cancer and controls were recruited from individuals undergoing minor, non-oncological surgery. Residential radon was measured using alpha track detectors. We included 521 individuals, 192 cases and 329 controls, 21% were males. We observed an odds ratio of 2.42 (95% CI 1.45-4.06) for individuals exposed to ≥200 Bq·m(-3) compared with those exposed to <100 Bq·m(-3). Environmental tobacco smoke exposure at home increased lung cancer risk in individuals with radon exposure>200 Bq·m(-3). Individuals exposed to environmental tobacco smoke and to radon concentrations>200 Bq·m(-3) had higher lung cancer risk than those exposed to lower radon concentrations and exposed to environmental tobacco smoke. Residential radon increases lung cancer risk in never-smokers. An association between residential radon exposure and environmental tobacco smoke on the risk of lung cancer might exist.

Fruit and vegetable consumption and lung cancer risk: a case-control study in Galicia, Spain.

Lung cancer has multiple risk factors and tobacco is the main one. Diet plays a role, but no clear effect has been consistently observed for different fruit and vegetable consumption. We aim to assess the association between fruit and vegetable consumption and lung cancer risk through a hospital-based case-control study in Spanish population. We recruited incident lung cancer cases in 2 Spanish hospitals from 2004 to 2008. Controls were individuals attending hospital for trivial surgery. Cases and controls were older than 30 and did not have a neoplasic history. We collected information on lifestyle with special emphases on tobacco and dietary habits. We included 371 cases and 496 controls. We found no protective effect for overall fruit consumption. For green leafy vegetables, the odds ratio (OR) was 0.92 [95% confidence interval (CI) = 0.32-2.69), and for other vegetables the OR was 0.77 (95% CI = 0.40-1.48) for the categories compared. We observed a reduced risk for broccoli and pumpkin intake. Although fruit consumption does not seem to be associated with a lower lung cancer risk, only the frequent consumption of specific green leafy vegetables and other vegetables might be associated with a reduced risk of lung cancer.

Leisure time activities related to carcinogen exposure and lung cancer risk in never smokers. A case-control study.

We aim to assess the relationship between leisure time activities related to exposure to carcinogenic substances and lung cancer risk in a hospital-based case-control study performed in never smokers. We included never smoking cases with anatomopathologically confirmed lung cancer and never smoking controls undergoing trivial surgery, at 8 Spanish hospitals. The study was conducted between January 2011 and June 2013. Participants were older than 30 and had no previous neoplasms. All were personally interviewed focusing on lifestyle, environmental tobacco smoke exposure, occupational history and leisure time activities (including duration of such activities). Results were analyzed through logistic regression and adjusted also by residential radon and education level. We included 513 never smokers, 191 cases and 322 controls. The OR for those performing the studied leisure time activities was 1.43 (95%CI 0.78-2.61). When we restricted the analysis to those performing do-it-yourself activities for more than 10 years the OR was 2.21 (95%CI 0.93-5.27). Environmental tobacco smoke exposure did not modify this association. The effect for the different lung cancer histological types was very close to significance for adenocarcinoma but only when these activities were performed for more than 10 years. We encourage health professionals to recommend protective measures for those individuals while performing these hobbies to reduce the risk of lung cancer.

Genome Wide Association Studies in Small-Cell Lung Cancer. A Systematic Review.

Small cell lung cancer (SCLC) is one of the deadliest forms of lung cancer, but few information exists regarding the role of genetics, particularly on Genome Wide Association Studies (GWAS). The aim of the study is to explore the evidence available obtained through GWAS studies for SCLC using a systematic review. We performed a literature search in the main databases until July 31st, 2023. We included all human based studies on GWAS for lung cancer which presented results for SCLC. Only studies with participants diagnosed of SCLC with anatomopathological confirmation were included. Fourteen studies were identified; 8 studies showed a relationship between ASCL1 overexpression and SCLC, which may regulate CHRNA5/A3/B4 cluster, producing a consequent nAChR overexpression. Nine papers, including 8 of the previous, found a positive association between SNPs located in chromosome 15 and SCLC. The most important cluster of genes found is CHRNA5/A3/B4 but the mechanism for the role of these genes is unclear. Kyoto Encyclopaedia of Genes and Genome (KEGG) shows that these receptors were found to be overexpressed where nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-Nitrosonornicotine (NNN) acts, involving different routes in SCLC carcinogenesis.

Quantifying indoor radon levels and determinants in schools: A case study in the radon-prone area Galicia-Norte de Portugal Euroregion.

Radon is a carcinogenic compound, and is particularly concerning in the education sector, where children and teachers may be exposed even longer than at home. Thus, this study intended to characterise radon in the indoor air of scholar environments in different provinces/districts of the Euroregion Galicia-Norte de Portugal. With a pioneering approach, this study evaluated the influence of specific factors/characteristics (location, type of management, construction material, season and floor within the building) and quantified their relative contribution to indoor radon levels. Radon was continuously monitored in 416 classrooms from school buildings located in urban and rural sites from different provinces/districts both in the regions of Galicia (A Coruña and Lugo provinces) and Portugal (Porto and Bragança districts), considering rooms for different age groups (from nursery schools to universities). Single and multivariate linear regression models were built considering the radon concentrations as the outcome variable and different room/building characteristics as predictor variables. Mean and median radon concentrations were 332 Bq·m-3 and 181 Bq·m-3, respectively. The radon concentrations observed are a public health concern, as almost 1/3 of the places monitored exceeded the reference limit value of the European legislation (300 Bq·m-3). Moreover, around 50 % of the indoor levels measured could be attributed to room/building characteristics: the building's location and the main construction material, as well as the occupants' age group, the floor within the building and the school's type of management (public/private). This study concluded that radon testing is needed in all school buildings and classrooms without exceptions. Thus, public administrations are urged to dedicate funds for testing, mitigation and public dissemination initiatives in schools. A special protocol for radon sampling in school buildings should also be developed.

A Genome-Wide Association Study of Small Cell Lung Cancer.

INTRODUCTION: Small cell lung cancer (SCLC) comprises 10-15% of all lung cancer cases and is the most aggressive histological type. Survival is poor and the molecular landscape of this disease is extraordinarily complex. The objective of this paper was to perform a Genome-Wide Association Study (GWAS) of this disease using a case-control study specifically designed for small cell lung cancer (SCLC). METHODS: Incident cases were consecutively recruited from 8 hospitals from different regions of Spain. Controls were recruited from the same hospitals using a frequency sampling based on age and sex distribution of cases. Biological samples were obtained along with detailed information on cases and controls lifestyle, including tobacco and radon exposure. RESULTS: We included 271 SCLC cases and 557 controls. We found evidence (p-values<10-5) of an association in the complete dataset for several loci, while MAP4 showed a significant association in the gene-based analysis. Pathway analysis suggested that ATR, ATRIP, MCM4, MCM5, ORC4, RPA3 and CDC25A genes have a role on the onset of SCLC. CONCLUSION: This study provides biological evidence for pathways related to SCLC, offering novel loci for further research.

Occupation as a risk factor of small cell lung cancer.

Small cell lung cancer (SCLC) comprises approximately 10% of all lung cancer cases. Tobacco is its main risk factor; however, occupation might play a role in this specific lung cancer subtype. The effect of occupation on SCLC risk has been hardly studied and therefore we aim to assess the role of occupation on the risk of SCLC. To do this, we designed a multicentric, hospital-based, case-control study. Cases consisted exclusively in SCLC patients and controls were recruited from patients having minor surgery at the participating hospitals. Face to face interviews emphasizing occupation and tobacco consumption were held and residential radon was also measured. Logistic regression models were adjusted with odds ratios with 95%CI as estimations of the effect. 423 cases and 905 controls were included. Smoking prevalence was higher in cases compared to controls. Those who worked in known-risk occupations for lung cancer showed an OR of 2.17 (95%CI 1.33; 3.52), with a similar risk when men were analysed separately. The results were adjusted by age, sex, smoking and indoor radon exposure. Those who worked in known-risk occupations and were moderate or heavy smokers had a SCLC risk of 12.19 (95%CI 5.68-26.38) compared with never or moderate smokers who had not worked in such occupations. Occupation is a relevant risk factor of SCLC, and it seems that its effect is boosted when tobacco smoking is present.