Lung emphysema and lung cancer: what do we know about it?

Emphysema and lung cancer (LC) are two diseases which share common risk factors, e.g., smoking. In recent years, many studies have sought to analyse this association. By way of illustration, we conducted a review of the scientific literature of the studies published to date, whose main designated aim was to demonstrate the relationship between emphysema and LC, and this association's influence on the histology, prognosis and molecular mechanisms responsible. We included over 40 studies (ranging from case-control and cohort studies to systematic reviews and meta-analyses), which highlight the association between emphysema and LC, independently of smoking habit. These studies also report a possible influence on histology, with adenocarcinoma being the most frequent lineage, and an association with poor prognosis, which affects both survival and post-operative complications. Oxidative stress, which generates chronic inflammatory status as well as the presence of certain polymorphisms in various genes (CYP1A1, TERT, CLPTM1L, ERK), gives rise-in the case of patients with emphysema-to alteration of cellular repair mechanisms, which in turn favours the proliferation of neoplastic epithelial cells responsible for the origin of LC

Genetic susceptibility, residential radon, and lung cancer in a radon prone area

INTRODUCTION: Radon exposure has been classified as the second cause of lung cancer, after tobacco, and the first in never smokers. GSTM1 and GSTT1 genes deletion increase the risk of lung cancer. We aim to know whether the risk of lung cancer because of residential radon is modulated by these genetic polymorphisms. METHODS: Hospital-based, case-control study where cases had confirmed lung cancer. Cases and controls did not have previous neoplasm and were older than 30. Controls attended hospital for noncomplex surgery. We analyzed the results for the whole sample and separately for never/light smokers and moderate/heavy smokers. RESULTS: Seven-hundred and ninety-two participants were analyzed. GSTM1 and GSTT1 deletion conferred an odds ratio (OR) of 1.38 (95% confidence interval [CI] 0.93-2.04) and 1.13 (95% CI 0.70-1.82), respectively. Individuals with GSTM1 present and residential radon concentrations higher than 148 Bq/m had an OR of 1.48 (95% CI 0.73-3.00), whereas those with GSTM1 deleted had an OR of 2.64 (95% CI 1.18-5.91) when compared with participants with GSTM1 present and radon concentrations below 50 Bq/m3. Similar results were observed for GSTT1 deletion. These results were basically the same for the moderate/heavy smokers' subgroup. CONCLUSIONS: The absence of GSTM1 and GSTT1 genes increases the risk of lung cancer because of radon exposure. These genes might modulate the carcinogenic pathway of alpha radiation. Further studies are warranted analyzing this association in never smokers

CYP1A1, mEH, and GSTM1 Polymophisms and Risk of Oral and Pharyngeal Cancer: A Spanish Case-Control Study

Background. Genetic polymorphisms of drug metabolizing enzymes involved in the detoxification pathways of carcinogenic substances may influence cancer risk. Methods. Case-control study that investigates the relationship between CYP1A1 Ile/Val, exon 4 mEH, and GSTM1 null genetic polymorphism and the risk of oral and pharyngeal cancer examining the interaction between these genes, tobacco, and alcohol. 92 incident cases and 130 consecutive hospital-based controls have been included. Results. No significant associations were found for any of the genotypes assessed. The estimated risk was slightly elevated in subjects with the wild type of the mEH gene and the null GSTM1 genotype. For exon 4 mEH heterozygous polymorphism, the risk was slightly lower for heavy smokers than for light smokers. The inverse association was observed for the GSTM1 null genotype. Conclusions. The results suggest that exon 4 mEH and GSTM1 null polymorphisms might influence oral and pharyngeal cancer

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

Impact of cardiovascular risk factors on the clinical presentation and survival of pulmonary embolism without identifiable risk factor

Background: The nature of pulmonary embolism (PE) without identifiable risk factor (IRF) remains unclear. The objective of this study is to investigate the potential relationship between cardiovascular risk factors (CVRFs) and PE without IRF (unprovoked) and assess their role as markers of disease severity and prognosis. Methods: A case-control study was performed of patients with PE admitted to our hospital [2010-2019]. Subjects with PE without IRF were included in the cohort of cases, whereas patients with PE with IRF were allocated to the control group. Variables of interest included age, active smoking, obesity, and diagnosis of arterial hypertension, dyslipidemia or diabetes mellitus. Results: A total of 1,166 patients were included in the study, of whom 64.2% had PE without IRF. The risk for PE without IRF increased with age [odds ratio (OR): 2.68; 95% confidence interval (CI): 1.95-3.68], arterial hypertension (OR: 1.63; 95% CI: 1.27-2.07), and dyslipidemia (OR: 1.63; 95% CI: 1.24-2.15). The risk for PE without IRF was higher as the number of CVRF increased, being 3.99 (95% CI: 2.02-7.90) for subjects with >/=3 CVRF. The percentage of high-risk unprovoked PE increased significantly as the number of CVRF rose [0.6% for no CVRF; 23.8% for a CRF, P/=3, P<0.001 (OR: 14.1; 95% CI: 4.06-49.4)]. No significant differences were observed in 1-month survival between cases and controls, whereas differences in 24-month survival reached significance. Conclusions: A relationship was observed between CVRF and PE without IRF, as the risk for unprovoked PE increased with the number of CVRF. In addition, the number of CVRF was associated with PE without IRF severity, but not with prognosis

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

<p>Abstract</p> <p>Background</p> <p>Radon is the second risk factor for lung cancer after tobacco consumption and therefore it is necessary to know the burden of disease due to its exposure. The objective of this study is to estimate radon-attributable lung cancer mortality in Galicia, a high emission area located at the Northwest Spain.</p> <p>Methods</p> <p>A prevalence-based attribution method was applied. Prevalence of tobacco use and radon exposure were obtained from a previously published study of the same area. Attributable mortality was calculated for each of six possible risk categories, based on radon exposure and smoking status. Two scenarios were used, with 37 Bq/m³and 148 Bq/m³as the respective radon exposure thresholds. As the observed mortality we used lung cancer mortality for 2001 from the Galician mortality registry.</p> <p>Results</p> <p>Mortality exclusively attributable to radon exposure ranged from 3% to 5% for both exposure thresholds, respectively. Attributable mortality to combined exposure to radon and smoking stood at around 22% for exposures above 148 Bq/m³. Applying the United States Environmental Protection Agency (EPA) action level, radon has a role in 25% of all lung cancers.</p> <p>Conclusions</p> <p>Although the estimates have been derived from a study with a relatively limited sample size, these results highlight the importance of radon exposure as a cause of lung cancer and its effect in terms of disease burden. Radon mitigation activities in the study area must therefore be enforced.</p

Associated Links Among Smoking, Chronic Obstructive Pulmonary Disease, and Small Cell Lung Cancer: A Pooled Analysis in the International Lung Cancer Consortium.

Background The high relapse and mortality rate of small-cell lung cancer (SCLC) fuels the need for epidemiologic study to aid in its prevention. Methods We included 24 studies from the ILCCO collaboration. Random-effects panel logistic regression and cubic spline regression were used to estimate the effects of smoking behaviors on SCLC risk and explore their non-linearity. Further, we explored whether the risk of smoking on SCLC was mediated through COPD. Findings Significant dose–response relationships of SCLC risk were observed for all quantitative smoking variables. Smoking pack-years were associated with a sharper increase of SCLC risk for pack-years ranged 0 to approximately 50. The former smokers with longer cessation showed a 43%quit_for_5–9 years to 89%quit_for_≥ 20 years declined SCLC risk vs. subjects who had quit smoking < 5 years. Compared with non-COPD subjects, smoking behaviors showed a significantly higher effect on SCLC risk among COPD subjects, and further, COPD patients showed a 1.86-fold higher risk of SCLC. Furthermore, smoking behaviors on SCLC risk were significantly mediated through COPD which accounted for 0.70% to 7.55% of total effects. Interpretation This is the largest pooling study that provides improved understanding of smoking on SCLC, and further demonstrates a causal pathway through COPD that warrants further experimental study. Abbreviations COPD, chronic obstructive pulmonary disease; CPG, cigarettes per day; ILCCO, International Lung Cancer Consortium; MeSH, medical subject headings; NSCLC, non-small cell lung cancer; OR, odds ratio; SCLC, small cell lung cancer