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.

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.

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.

Magnetic resonance imaging for the study of mediastinal adenopathies in lung cancer: Comparison with standard tests.

BACKGROUND: Lung cancer is the second most common cancer in both men and women. Mediastinal lymph node involvement in these patients, determined by imaging tests, indicates prognosis and modifies therapeutic attitude. PURPOSE: The aim of this study was to analyze the diagnostic capacity of magnetic resonance imaging (MRI) in the study of the mediastinum in comparison with conventional tests (computed tomography [CT] and positron-emission tomography [PET] or PET/CT scans), taking histology as the gold standard. MATERIALS AND METHODS: An observational study was conducted on 16 patients with suspicion of primary lung cancer (June 2016 through December 2018). We studied their demographic characteristics and used CT, PET, or PET/CT scans and MRI (diffusion-weighted imaging-MRI sequence) to examine mediastinal disease and compare MRIs diagnostic yield and percentage agreement to that of conventional tests. RESULTS: As compared to CT and PET scanning, MRI displayed a very low sensitivity and a specificity of 90 and 88%, respectively; positive predictive value was 0.67 (both) and negative predictive value (NPV) was 0.28 and 0.22, respectively. MRI showed a high degree of agreement in lymph node diagnosis when compared with histology (91.2%; P = 0.001): specificity in this case was high (E = 0.94), as was the NPV (NPV = 0.97). CONCLUSIONS: The results of this study would appear to indicate that MRI could play a relevant role in mediastinal staging of lung cancer. More prospective, multicenter studies are, however, needed to be able to draw up firm recommendations about the role of MRI and its place in lung cancer staging.

Usefulness of Positron Emission Tomography in the Examination of Hilar and Mediastinal Lymphadenopathies in Patients with Suspicion of Lung Cancer.

Introduction: Lung cancer is a major health problem. Mediastinal staging performed with the aid of imaging techniques is essential for appropriate disease treatment and prognosis. Accordingly, this study aimed to ascertain the usefulness of positron emission tomography (PET) in mediastinal staging, establish the best maximum standardized uptake value (SUVmax) cutoff point, compare its usefulness to that of computed tomography (CT), and determine the influence of histological tumour subtype. Methods: We conducted a retrospective study across a period of 3 years on 128 patients with suspicion of lung cancer and analyzed their demographic and radiological characteristics using CT and PET to perform the mediastinal examination. Histology was regarded as the gold standard. Results: PET displayed a high sensitivity (95%) and negative predictive value (NPV) (92%), outperforming CT (89% and 85%, respectively). Percentage agreement with histology was also higher (0.207 and 0.241 for CT and PET, respectively; p < 0.001). Taking an SUVmax value of 0.5 as that which would ensure greatest diagnostic accuracy, S and NPV were 100%, though percentage agreement did not increase (0.189; p < 0.001). PET discriminatory power was not affected by histological tumour subtype. Conclusions: The results of our study indicate that PET might be a useful test for examination of the mediastinum in lung cancer patients. Its high NPV suggests that the absence of mediastinal uptake could be used to proceed to surgical treatment without the need for further tests or examinations. Nevertheless, studies directly aimed to answer this specific question are needed.

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.

Environmental tobacco smoke exposure and EGFR and ALK alterations in never smokers' lung cancer. Results from the LCRINS study.

Environmental tobacco smoke (ETS) exposure is a main risk factor of lung cancer in never smokers. Epidermal Growth Factor Receptor (EGFR) mutations and ALK translocations are more frequent in never smokers' lung cancer than in ever-smokers. We performed a multicenter case-control study to assess if ETS exposure is associated with the presence of EGFR mutations and its types and if ALK translocations were related with ETS exposure. All patients were never smokers and had confirmed lung cancer diagnosis. ETS exposure during childhood showed a negative association on the probability of EGRF mutation though not significant. Exposure during adulthood, at home or at workplace, did not show any association with EGFR mutation. The mutation type L858R seemed the most associated with a lower probability of EGFR alterations for ETS exposure at home in adult life. There is no apparent association between ETS exposure and ALK translocation. These results might suggest that ETS exposure during childhood or at home in adult life could influence the EGFR mutations profile in lung cancer in never smokers, reducing the probability of presenting EFGR mutation.

Residential radon and lung cancer characteristics in never smokers.

PURPOSE: The aim of this study is to assess if there is a relationship between residential radon and lung cancer histological types and patients' age at diagnosis. MATERIALS AND METHODS: We conducted a multicenter hospital-based case-control study with eight participating hospitals. We included 216 never-smoking cases with primary lung cancer and 329 never-smoking controls. Controls were frequency matched with cases on age and sex distribution. Of them, 198 cases (91.7%) and 275 controls (83.5%) had residential radon measurements. RESULTS: Lung cancer risk reached statistical significance only for adenocarcinoma (Odds ratio [OR] 2.19; 95% Confidence interval [CI] 1.44-3.33), for other histologies the results were marginally significant. Residential radon level was higher for patients diagnosed before 50 and 60 years old than for older lung cancer cases. CONCLUSIONS: Residential radon in never smokers seems to be a risk factor for all lung cancer histologies. Individuals diagnosed at a younger age have a higher residential radon concentration, suggesting an accumulative effect on lung cancer appearance.

Alpha-1 Antitrypsin Deficiency and Lung Cancer Risk: A Case-Control Study in Never-Smokers.

BACKGROUND: Never-smokers comprise up to 25% of all lung cancer cases. They could have different molecular pathways for lung cancer induction compared with smokers. Alpha-1 antitrypsin (AAT) deficiency is a hereditary trait whose main characteristic is early onset of lung emphysema. Our aim is to know if AAT-deficient carriers have a higher risk of lung cancer in a study performed exclusively in never-smokers. METHODS: We designed a multicentre hospital-based case-control study, which included incident never-smoking lung cancer cases. Controls were never-smokers attending nonmajor surgery at the participating hospitals. Controls were frequency matched on age and gender with cases. We determined AAT variants (alleles S and Z) through polymerase chain reaction. RESULTS: Two hundred and twelve cases and 318 controls were included. PiSS individuals showed a lung cancer risk of 4.64 (95% confidence interval: 1.08-19.92) compared with those with normal genotype (PiMM). When the analysis was restricted to women, the risk for PiSS increased to 7.58 (95% confidence interval: 1.40-40.87). This risk for homozygous SS was even higher for individuals exposed to environmental tobacco smoke (greater than 20 years). The presence of other alleles did not show any effect on lung cancer risk. CONCLUSIONS: Never smoking SS homozygous individuals pose an increased risk of lung cancer. The risk is higher for individuals exposed to environmental tobacco smoke.

Use of Magnetic Resonance Imaging for N-Staging in Patients with Non-Small Cell Lung Cancer. A Systematic Review / Uso de las imágenes por resonancia magnética para la estadificación ganglionar (N) del cáncer de pulmón de no microcítico. Revisión sistemática

Introduction: The aim of this study is to assess the diagnostic value of the magnetic resonance imaging (MRI) in differentiating metastasic from non-metastatic lymph nodes in NSCLC patients compared with computed tomography (CT) and fluorodeoxyglucose (FDG) - positron emission tomography (PET) or both combined. Methods: Twenty-three studies (19 studies and 4 meta-analysis) with sample size ranging between 22 and 250 patients were included in this analysis. MRI, regardless of the sequence obtained, where used for the evaluation of N-staging of NSCLC. Histopathology results and clinical or imaging follow-up were used as the reference standard. Studies were excluded if the sample size was less than 20 cases, if less than 10 lymph nodes assessment were presented or studies where standard reference was not used. Papers not reporting sufficient data were also excluded. Results: As compared to CT and PET, MRI demonstrated a higher sensitivity, specificity and diagnostic accuracy in the diagnosis of metastatic or non-metastatic lymph nodes in N-staging in NSCLC patients. No study considered MRI inferior than conventional techniques (CT, PET or PET/CT). Other outstanding results of this review are fewer false positives with MRI in comparison with PET, their superiority over PET/CT to detect non-resectable lung cancer, to diagnosing infiltration of adjacent structures or brain metastasis and detecting small nodules. Conclusion: MRI has shown at least similar or better results in diagnostic accuracy to differentiate metastatic from non-metastatic mediastinal lymph nodes. This suggests that MRI could play a significant role in mediastinal NSCLC staging

Introducción: El objetivo de este trabajo es evaluar el potencial diagnóstico de las imágenes por resonancia magnética (RM) para identificar nódulos linfáticos metastásicos frente aquellos no metastásicos en pacientes con cáncer de pulmón no microcítico (CPNM) en comparación con la tomografía computarizada (TC), la tomografía por emisión de positrones con 18F-fluorodesoxiglucosa (PET-FDG) o ambas técnicas combinadas. Métodos: En el análisis se incluyeron 23 estudios (19 estudios y 4 metaanálisis) con tamaños de muestra entre 22 y 250 pacientes. Para la estadificación ganglionar (N) del CPNM se utilizaron imágenes de RM independientemente de la secuencia obtenida. Como estándar de referencia se usaron los resultados histopatológicos y el seguimiento clínico o por imagen. Se excluyeron aquellos estudios con tamaños muestrales menores de 20 casos, aquellos con menos de 10 nódulos linfáticos evaluados o estudios en los que no se usó un estándar de referencia. También se excluyeron los artículos que no presentaron suficientes datos. Resultados: Se observó que la RM presentaba mayor sensibilidad, especificidad y precisión en la estadificación ganglionar (N) y el diagnóstico de nódulos linfáticos metastásicos o no metastásicos en pacientes con CPNM en comparación con la TC y el PET. Ningún estudio consideró a la RM inferior con respecto a otras técnicas convencionales (TC, PET y PET/TC). Otros resultados destacables de esta revisión son que con la RM se originaron menos falsos positivos en comparación con el PET, y su superioridad respecto al PET/TC en la detección de tumores de pulmón no operables, en el diagnóstico de infiltración en estructuras adyacentes o metástasis cerebrales, así como en la detección de nódulos de pequeño tamaño. Conclusión: La RM dio lugar a mejores resultados o, al menos comparables, relacionados con la precisión diagnóstica para diferenciar nódulos linfáticos metastásicos de no metastásicos. Esto sugiere que la RM podría jugar un papel importante en la estadificación mediastinal en pacientes con CPNM

Exposure to residential radon and lung cancer in never-smokers: the preliminary results of the LCRINS study.

INTRODUCTION AND OBJECTIVE: Residential radon is the second most important risk factor for lung cancer and the first among never-smokers. The objective of this study is to report the concentrations of residential radon in a series of never-smoker cases recruited in a multicenter study of cases and controls in northwestern Spain. In this study, all the hospitals in the Spanish province of Galicia and one from Asturias participated. PATIENTS AND METHODS: The present article includes a series of cases with residential radon measurements. All the subjects were personally interviewed, 3 ml of blood were taken from each, and they were each given instructions about how to place a residential radon detector in their homes. RESULTS: Sixty-nine case subjects were recruited, 84% of whom were women with a mean age of 71, and 81% of whom had adenocarcinoma. The average concentration of residential radon in the cases was 237 Bq/m(3), while the average concentration in the Galician population is 79 Bq/m(3). No relationship was observed between the concentration of residential radon and either sex or age at the time of diagnosis of the cases, but there was a tendency towards having a greater concentration in those diagnosed with small-cell and large-cell carcinoma. CONCLUSIONS: The concentrations of residential radon in the cases included are very high at about three times the average concentration of residential radon to which the general population of Galicia is exposed.

Exposición a radón residencial y cáncer de pulmón en nunca fumadores. Resultados preliminares del estudio LCRINS / Exposure to Residential Radon and Lung Cancer in Never-Smokers: the Preliminary Results of the LCRINS Study

Introducción y objetivo: El radón residencial es el segundo factor de riesgo del cáncer de pulmón y el primero en nunca fumadores. El objetivo de este estudio es describir la concentración de radón residencial en una serie de casos nunca fumadores reclutados en un estudio multicéntrico de casos y controles en el noroeste de España. En este estudio participan todos los hospitales gallegos y uno asturiano. Pacientes y métodos: En el presente artículo se incluye la serie de casos con mediciones de radón residencial. A todos los casos se les realiza una entrevista personal, se les extraen 3ml de sangre total y se les dan instrucciones para la colocación de un detector de radón residencial en su domicilio. Resultados: Se han incluido 69 casos (el 84% mujeres), con una edad media de 71 años y el 81% con adenocarcinoma. La concentración mediana de radón residencial en los casos ha sido de 237Bq/m3, mientras que la concentración mediana en la población gallega es de 79Bq/m3. No se ha observado relación entre la concentración de radón residencial y el sexo o la edad al diagnóstico de los casos, pero sí hay una tendencia a tener mayor concentración en los diagnosticados de carcinoma de células pequeñas y de células grandes. Conclusiones: Las concentraciones de radón residencial en los casos incluidos son muy elevadas, del orden de 3 veces la concentración mediana de radón residencial a la que está expuesta la población general gallega(AU)

Introduction and objective: Residential radon is the second most important risk factor for lung cancer and the first among never-smokers. The objective of this study is to report the concentrations of residential radon in a series of never-smoker cases recruited in a multicenter study of cases and controls in northwestern Spain. In this study, all the hospitals in the Spanish province of Galicia and one from Asturias participated. Patients and methods: The present article includes a series of cases with residential radon measurements. All the subjects were personally interviewed, 3ml of blood were taken from each, and they were each given instructions about how to place a residential radon detector in their homes. Results: Sixty-nine case subjects were recruited, 84% of whom were women with a mean age of 71, and 81% of whom had adenocarcinoma. The average concentration of residential radon in the cases was 237Bq/m3, while the average concentration in the Galician population is 79Bq/m3. No relationship was observed between the concentration of residential radon and either sex or age at the time of diagnosis of the cases, but there was a tendency towards having a greater concentration in those diagnosed with small-cell and large-cell carcinoma. Conclusions: The concentrations of residential radon in the cases included are very high at about three times the average concentration of residential radon to which the general population of Galicia is exposed(AU)