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 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.

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.

An Innovative Tool to Control Occupational Radon Exposure.

After smoking, indoor radon is the main contributor to lung cancer in many countries. The European Union (EU) Directive 2013/59/Euratom establishes a maximum reference level of 300 Bq/m3 of radon concentration in the workplace, and an effective dose limit of 20 mSv per year for workers. If the radon concentration in a workplace exceeds the reference level, constructive mitigation applies. When constructive mitigation is not feasible, we propose to keep workers' effective dose below 6 mSv per year (category B of exposed workers) by controlling occupancy time. Setting the maximum annual dose at 6 mSv protects workers' health and eases the regulatory requirements for employers. If multisite workers are present, each worker has to be monitored individually by tracking the time spent and the radon concentration at each worksite. This paper shows a software tool for employers to perform this complex tracking in an accurate, conservative, and transparent manner, and in compliance with the EU by-laws.

Residential Radon in Manizales, Colombia: Results of a Pilot Study.

Radon is a colorless, odorless, and tasteless noble gas, causally related with the onset of lung cancer. We aimed to describe the distribution of radon exposure in the municipality of Manizales, Colombia, in order to estimate the population's exposure and establish the percentage of dwellings that surpass reference levels. A cross-sectional study representing all geographical areas was carried out by measuring indoor radon concentrations. Participants answered a short questionnaire. Alpha-track type radon detectors were installed in all residences for six months. The detectors were subsequently processed at the Galician Radon Laboratory, an accredited laboratory at the University of Santiago de Compostela. A total of 202 homes were measured. Seventy-seven percent of the sampled houses were three stories high, their median age was 30 years, and half were inhabited by three people or fewer. For most dwellings, the building materials of walls and flooring were brick and covered cement, respectively. Results showed a geometric mean of radon concentration of 8.5 Bq/m3 and a maximum value of 50 Bq/m3. No statistically significant differences were found either between the geometric mean of the dwelling's site, the height at which detectors were placed inside the home, or the wall and flooring materials, or between mean 222Rn concentrations in rural and urban areas. No dwelling surpassed the 222Rn reference level established by the WHO. This study shows that residential radon levels in Manizales, Colombia, seem to be low, though a more in-depth approach should be carried out. Despite these results, it is essential to create a national radon program and establish a radon concentration reference level for Colombia in line with international recommendations.

Epidemiology of stage III lung cancer: frequency, diagnostic characteristics, and survival.

Stage III non-small cell lung cancer (NSCLC) includes a highly heterogeneous group of patients with differences in the extent and localization of disease. Many aspects of stage III disease are controversial. The data supporting treatment approaches are often subject to a number of limitations, due to the heterogeneous patient populations involved in the trials. Furthermore, the definition of stage III disease has changed over time, and early studies were frequently inadequately powered to detect small differences in therapeutic outcome, were not randomized, or had a limited follow-up times. Major improvements in therapy, including the use of more active chemotherapy agents and refinements in radiation and surgical techniques, also limit the interpretation of earlier clinical trials. Lastly, improvements in pretreatment staging have led to reclassification of patients with relatively minimal metastatic disease as stage IV rather than stage III, leading to an apparent increase in the overall survival of both stage III and IV patients. Median overall stage III NSCLC survival ranges from 9 to 34 months. Higher survival rates are observed in younger Caucasian women with good performance status, adenocarcinoma, mutations, stage IIIA, and in patients with multidisciplinary-team-based diagnoses.

Indoor Radon Exposure and COPD, Synergic Association? A Multicentric, Hospital-Based Case-Control Study in a Radon-Prone Area.

BACKGROUND: COPD is a multifactorial disease which causes considerable mortality and morbidity worldwide. Previous studies assessing the possible relationship between indoor radon exposure and COPD have shown inconclusive results. METHODS: A multicentric, hospital-based, case-control study was conducted in a Spanish radon-prone area. COPD cases were confirmed by spirometry and controls were selected due to trivial surgery or procedures not related to tobacco consumption. All participants had to have lived for at least 15 years in the same dwelling. Radon measurements were conducted individually in dwellings using alpha-track detectors. Results were obtained using multivariate logistic regression. RESULTS: 189 cases and 747 controls took part. There was no significant association between residential radon concentrations and COPD onset with a OR of 1.12 (95%CI 0.41-3.06) for individuals exposed to more than 200Bq/m3 compared to those exposed to less than 50Bq/m3. Heavy smokers seem to increase their COPD risk if exposed to higher radon concentrations vs those exposed to lower concentrations. There was a statistically significant synergy index between radon exposure and tobacco consumption, S-index 11.60 (95%CI 3.71-36.26). Indoor radon concentration was higher in never/light smokers with COPD compared to controls. CONCLUSIONS: No association between indoor radon and COPD has been observed. However, there might be some effect modification on the COPD risk in heavy smokers when high radon exposure is present. This is supported by the additive synergy observed. Also, a possible association between indoor radon and COPD onset in never and light smokers needs to be further studied.

Radon Exposure and Neurodegenerative Disease.

Background: To carry out a systematic review of scientific literature about the association between radon exposure and neurodegenerative diseases. Methods: We performed a bibliographic search in the following databases: Pub med (Medline), Cochrane, BioMed Central and Web of Science. We collected the data by following a predetermined search strategy in which several terms werecombined. After an initial search, 77 articles were obtained.10 of which fulfilled the inclusion criteria. Five of these 10 studies were related to multiple sclerosis (MS), 2 were about motor neuron diseases (MND), in particular amyotrophic lateral sclerosis (ALS) and 3 were related to both Alzheimer's disease (AD) and Parkinson's disease (PD). Results: The majority of the included articles, suggested a possible association between radon exposure and a subsequent development of neurodegenerative diseases. Some of the studies that obtained statistically significant resultsrevealed a possible association between radon exposure and an increase in MS prevalence. Furthermore, it was also suggested that radon exposure increases MND and AD mortality. Regarding AD and PD, it was observed that certainde cay products of radon-222 (222Rn), specifically polonium-210 (210Po) and bismuth-210 (210Bi), present a characteristic distributionpattern within the brain anatomy. However, the study with the highest scientific evidence included in this review, which investigated a possible association between the concentration of residential radon gas and the MS incidence, revealed no significant results. Conclusions: It cannot be concluded, although it is observed, that there is a possible causal association between radon exposure and neurodegenerative diseases. Most of the available studies are ecological so, studies of higher statistical evidence are needed to establish a causal relationship. Further research is needed on this topic.

Exposure to Residential Radon and COPD: A Systematic Review.

Introduction: The aim of this study was to analyse the relationship between exposure to residential radon and chronic obstructive pulmonary disease (COPD) by means of a systematic review. Material and Methods: A search was conducted in PubMed and OVID for papers making reference to the radon-COPD relationship. No search filters were applied, whether by date of publication, study type or sample size. All studies not written in English or Spanish were discarded. Results: A total of 174 and 57 papers were found in PubMed and OVID, respectively: of these, 13 (11 on miners and 2 on the general population) fulfilled the inclusion criteria. Only four of the studies on cohorts of miners analysed COPD as a specific disease, and only one reported statistically significant results. In addition, many of these studies lacked information on tobacco use among miners. In contrast, studies conducted on the general public showed an association between mortality and hospital admissions, on the one hand, and residential radon on the other. Conclusion: There are not enough studies to provide a basis for confirming or ruling out an association between radon exposure and COPD. Nonetheless, the most recent general population studies point to evidence of a possible association. In view of the heterogeneity of available studies, it is impossible to say whether this gas may or may not affect COPD morbidity and mortality, until such a time as further studies are carried out.

Indoor Radon Exposure and COPD, Synergic Association? A Multicentric, Hospital-Based Case-Control Study in a Radon-Prone Area.

BACKGROUND: COPD is a multifactorial disease which causes considerable mortality and morbidity worldwide. Previous studies assessing the possible relationship between indoor radon exposure and COPD have shown inconclusive results. METHODS: A multicentric, hospital-based, case-control study was conducted in a Spanish radon-prone area. COPD cases were confirmed by spirometry and controls were selected due to trivial surgery or procedures not related to tobacco consumption. All participants had to have lived for at least 15 years in the same dwelling. Radon measurements were conducted individually in dwellings using alpha-track detectors. Results were obtained using multivariate logistic regression. RESULTS: 189 cases and 747 controls took part. There was no significant association between residential radon concentrations and COPD onset with a OR of 1.12 (95%CI 0.41-3.06) for individuals exposed to more than 200Bq/m3 compared to those exposed to less than 50Bq/m3. Heavy smokers seem to increase their COPD risk if exposed to higher radon concentrations vs those exposed to lower concentrations. There was a statistically significant synergy index between radon exposure and tobacco consumption, S-index 11.60 (95%CI 3.71-36.26). Indoor radon concentration was higher in never/light smokers with COPD compared to controls. CONCLUSIONS: No association between indoor radon and COPD has been observed. However, there might be some effect modification on the COPD risk in heavy smokers when high radon exposure is present. This is supported by the additive synergy observed. Also, a possible association between indoor radon and COPD onset in never and light smokers needs to be further studied.

Polymorphisms in the BER and NER pathways and their influence on survival and toxicity in never-smokers with lung cancer.

Polymorphisms in DNA repair pathways may play a relevant role in lung cancer survival in never-smokers. Furthermore, they could be implicated in the response to chemotherapy and toxicity of platinum agents. The aim of this study was to evaluate the influence of various genetic polymorphisms in the BER and NER DNA repair pathways on survival and toxicity in never-smoker LC patients. The study included never-smokers LC cases diagnosed from 2011 through 2019, belonging to the Lung Cancer Research In Never Smokers study. A total of 356 never-smokers cases participated (79% women; 83% adenocarcinoma and 65% stage IV). Survival at 3 and 5 years from diagnosis was not associated with genetic polymorphisms, except in the subgroup of patients who received radiotherapy or chemo-radiotherapy, and presented with ERCC1 rs3212986 polymorphism. There was greater toxicity in those presenting OGG1 rs1052133 (CG) and ERCC1 rs11615 polymorphisms among patients treated with radiotherapy or chemo-radiotherapy, respectively. In general, polymorphisms in the BER and NER pathways do not seem to play a relevant role in survival and response to treatment among never-smoker LC patients.

Lung cancer survival in never-smokers and exposure to residential radon: Results of the LCRINS study.

We aimed to evaluate lung cancer survival in never-smokers, both overall and specifically by sex, exposure to residential-radon, age, histological type, and diagnostic stage. We included lung cancer cases diagnosed in a multicentre, hospital-based, case-control-study of never-smoker patients, diagnosed from January-2011 to March-2015 (Lung Cancer Research In Never Smokers study). 369 never-smokers (79% women; median age 71 years; 80% adenocarcinoma; 66% stage IV) were included. Median overall survival, and at one, 3 and 5 years of diagnosis was 18.3 months, 61%, 32% and 22%, respectively. Higher median survival rates were obtained for: younger age, adenocarcinoma, actionable mutations, and earlier-stage at diagnosis. Higher indoor radon showed a higher risk of death in multivariate analysis. Median lung cancer survival in never-smokers seems higher than that in ever-smokers. Patients with actionable mutations have a significantly higher survival. Higher indoor-radon exposure has a negative effect on survival.

Lung cancer survival among never smokers.

Lung cancer incidence among never smokers has increased in recent decades with 10-30% of all lung cancers occurring in never smokers, where exposure to residential radon is the leading cause of this disease. Lung cancer survival is low, ranging from 12% to 16% at 5 years of diagnosis. There is scant evidence to date on survival from this disease in never smokers. We aim to evaluate lung cancer survival in never smokers and ascertain whether there might be differences regarding smokers, through a systematic review applying predefined inclusion and exclusion criteria. 17 Studies were included. Never-smoker lung cancer patients seem to experience longer survival times than do smokers or ex-smokers. Lung cancer in never smokers displays distinctive clinical characteristics, is more frequent among women, is diagnosed at more advanced stages, and the predominant histologic type is adenocarcinoma. Further studies are necessary to ascertain lung cancer survival among never smokers.