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

Indoor Radon and Lung Cancer Risk. A Pooling Study on the Second Risk Factor for Lung Cancer

Background. Residential radon is the second risk factor of lung cancer following tobacco consumption, according to WHO (World Health Organization) and United States EPA statements. It is recognized as the first cause of lung cancer in never-smokers by both organizations. Nevertheless, case-control studies performed in radon prone areas are still scarce and with limited sample sizes. We aim to know the relationship between residential radon and lung cancer risk in a study performed in a radon-prone area, and where inhabitants live for a long time in the same dwelling. Method. We have pooled results from 5 different case-control studies performed in the same geographical area to assess the relationship between indoor radon and lung cancer. One of these studies was focused specifically in never smokers and other in Small Cell Lung Cancer. All cases and controls were older than 30 and cases had a confirmed diagnosis of lung cancer. Controls were selected for attending hospital for trivial surgery. Controls were selected through a frequency-based sampling based on age and gender distribution of cases. The information and questionnaires collected was the same in all studies, with special focus on tobacco consumption. Radon devices of an alpha track type were placed at the participants’ homes for at least three months. Odds Ratios of lung cancer due to radon exposure have been calculated adjusted by age, gender, and tobacco consumption. Result. We included 1691 cases and 1698 controls. Median age was 63 and 67, respectively, and females comprised 33% of both cases and controls. Adenocarcinoma was the most frequent histology (43%) and participants lived a median of 30 years in the same dwelling. The table show the risk of lung cancer due to radon exposure. Conclusion. Residential radon is a relevant risk factor for lung cancer, even below concentrations established as safe by USEPA and WHO

Small-cell lung cancer in never-smokers

Background: Lung cancer is a public health problem worldwide. Small-cell lung cancer (SCLC) is the most aggressive histologic type, with a 5-year survival <10%. SCLC is closely associated with tobacco consumption and infrequent in never-smokers. We aim to describe SCLC characteristics in never-smokers recruited in a radon-prone area. Patients and methods: We designed a multicentric case series where SCLC cases were recruited consecutively following histologic confirmation. Detailed information was obtained for indoor radon exposure, occupation and environmental tobacco smoke. We also collected different clinical characteristics such as extended or limited disease at diagnosis. Results: We recruited 32 never-smoking SCLC cases. Median age was 75 years and 87.5% were women; 47% had extended disease. Median radon concentration was 182 Bq/m3. There were no statistically significant differences in residential radon concentration neither regarding age at diagnosis nor regarding sex. The most frequent symptoms were constitutional syndrome (23.1%) and coughing (23.1%). As much as 63% of cases had an Eastern Cooperative Oncology Group Study (ECOG) status of 0-2. The 1- and 2-year survival rates were 34.4% and 21.9%, respectively. The 2-year survival rate with a localized tumor was 26.7%, compared with 18.8% for extended disease. Conclusions: These results show, for the first time, that indoor radon might not be associated with SCLC characteristics at diagnosis in never-smokers, and also confirms the low survival of this aggressive type of lung cancer also for never-smokersThis work was supported by the Instituto de Salud Carlos III (ISCIII)/PI15/01211/Cofinanciado FEDER, Spanish Society of Neumology and Thoracic Surgery (Project number 848. 2019 call

Redox imbalance in lung cancer of patients with underlying chronic respiratory conditions

Chronic respiratory diseases such as obstructive pulmonary disease (COPD) and oxidative stress may underlie lung cancer (LC). We hypothesized that the profile of oxidative and antioxidant events may differ in lung tumors and blood compartments of patients with non-small cell LC (NSCLC) with and without COPD. Redox markers (immunoblotting, ELISA, chemiluminescence, 2D electrophoresis and proteomics) were analyzed in blood samples of 17 control subjects and 80 LC patients (59 LC-COPD and 21 LC) and lung specimens (tumor and nontumor) from those undergoing thoracotomy (35 patients: 23 LC-COPD and 12 LC). As smoking history was more prevalent in LC-COPD patients, these were further analyzed post hoc as heavy and moderate smokers (cutoff, 60 pack-years). Malondialdehyde (MDA)-protein adducts and SOD1 levels were higher in tumor and nontumor samples of LC-COPD than in LC. In tumors compared with nontumors, SOD2 protein content was greater, whereas catalase levels were decreased in both LC and LC-COPD patients. Blood superoxide anion levels, protein carbonylation and nitration were greater in LC and LC-COPD patients than in the controls, and in the latter patients compared with the former. Systemic superoxide anion, protein carbonyls and nitrotyrosine above specific cutoff values best identified underlying COPD among all patients. Smoking did not influence the study results. A differential expression profile of oxidative stress markers exists in blood and, to a lesser extent, in the tumors of LC-COPD patients. These findings suggest that systemic oxidative stress and lung antioxidants (potential biomarkers) may predispose patients with chronic respiratory diseases to a higher risk for LC.This study has been supported with funding by SEPAR 2008, FUCAP 2009, FUCAP 2011, FUCAP 2012, FIS 11/02029 (FEDER), FIS 14/00713 (FEDER), SAF2011-26908, and CIBERES (Instituto de Salud Carlos III)

The IASLC Lung Cancer Staging Project: External Validation of the Revision of the TNM Stage Groupings in the Eighth Edition of the TNM Classification of Lung Cancer

Introduction Revisions to the TNM stage classifications for lung cancer, informed by the international database (N = 94,708) of the International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee, need external validation. The objective was to externally validate the revisions by using the National Cancer Data Base (NCDB) of the American College of Surgeons. Methods Cases presenting from 2000 through 2012 were drawn from the NCDB and reclassified according to the eighth edition stage classification. Clinically and pathologically staged subsets of NSCLC were analyzed separately. The T, N, and overall TNM classifications were evaluated according to clinical, pathologic, and â\u80\u9cbestâ\u80\u9d stage (N = 780,294). Multivariate analyses were carried out to adjust for various confounding factors. A combined analysis of the NSCLC cases from both databases was performed to explore differences in overall survival prognosis between the two databases. Results The databases differed in terms of key factors related to data source. Survival was greater in the IASLC database for all stage categories. However, the eighth edition TNM stage classification system demonstrated consistent ability to discriminate TNM categories and stage groups for clinical and pathologic stage. Conclusions The IASLC revisions made for the eighth edition of lung cancer staging are validated by this analysis of the NCDB database by the ordering, statistical differences, and homogeneity within stage groups and by the consistency within analyses of specific cohorts