In this review, we summarize and discuss the evidence regarding the interaction between air pollution, especially particulate matter (PM), and genomic instability. PM has been widely studied in the ...context of several diseases, and its role in lung carcinogenesis gained relevance due to an increase in cancer cases for which smoking does not seem to represent the main risk factor. According to epidemiological and toxicological evidence, PM acts as a carcinogenic factor in humans, inducing high rates of genomic alterations. Here, we discuss not only how PM is capable of inducing genomic instability during the carcinogenic process but also how our genetic background influences the response to the sources of damage.
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•Air pollution represents a worldwide problem with impact on human health.•Particulate matter (PM) has a recognized carcinogenic potential in humans.•Lung cancer susceptibility depends on gene-environment interactions.•Epidemiological and experimental evidence links PM exposure to genomic instability.•PM and genomic instability are co-dependent factors during cancer continuum.
We summarize the association between particulate matter (a component of air pollution) and genomic instability as well as discuss how new strategies to study the impact of air pollution on genomic instability and lung-cancer development could improve our understanding of the lung-cancer genome.
Air pollution has been recognized as a global health problem, causing around 7 million deaths worldwide and representing one of the highest environmental crises that we are now facing. Close to 30% ...of new lung cancer cases are associated with air pollution, and the impact is more evident in major cities. In this review, we summarize and discuss the evidence regarding the effect of particulate matter (PM) and its impact in carcinogenesis, considering the "hallmarks of cancer" described by Hanahan and Weinberg in 2000 and 2011 as a guide to describing the findings that support the impact of particulate matter during the cancer continuum.
In cells, oxidative stress is an imbalance between the production/accumulation of oxidants and the ability of the antioxidant system to detoxify these reactive products. Reactive oxygen species ...(ROS), cause multiple cellular damages through their interaction with biomolecules such as lipids, proteins, and DNA. Genotoxic damage caused by oxidative stress has become relevant since it can lead to mutation and play a central role in malignant transformation. The evidence describes chronic oxidative stress as an important factor implicated in all stages of the multistep carcinogenic process: initiation, promotion, and progression. In recent years, ambient air pollution by particulate matter (PM) has been cataloged as a cancer risk factor, increasing the incidence of different types of tumors. Epidemiological and toxicological evidence shows how PM-induced oxidative stress could mediate multiple events oriented to carcinogenesis, such as proliferative signaling, evasion of growth suppressors, resistance to cell death, induction of angiogenesis, and activation of invasion/metastasis pathways. In this review, we summarize the findings regarding the involvement of oxidative and genotoxic mechanisms generated by PM in malignant cell transformation. We also discuss the importance of new approaches oriented to studying the development of tumors associated with PM with more accuracy, pursuing the goal of weighing the impact of oxidative stress and genotoxicity as one of the main mechanisms associated with its carcinogenic potential.
To determine the prevalence of influenza vaccination in chronic obstructive pulmonary disease (COPD) patients and its effect on COPD exacerbations, we conducted a retrospective population-based ...cohort study analyzing real-life data. We included all registered COPD patients ≥40 years old using respiratory medication during the study period (2012–2013). Influenza vaccination during the 2012/2013 campaign was the parameter studied. Moderate and severe exacerbations during 2013 were the dependent outcome variables. Logistic regression adjusting for age, gender, concomitant asthma diagnosis, COPD severity, smoking status, number of moderate and severe exacerbations the previous year, and comorbidities was performed, and 59.6% of the patients received seasonal influenza vaccination. The percentage of patients with exacerbations was higher among those vaccinated. Influenza vaccination had a statistically significantly negative (non-protective) crude effect favoring the risk of severe exacerbations: OR: 1.20 (95% CI; 1.05–1.37). This association diminished and lost statistical significance after adjustment: aOR: 0.93 (95% CI; 0.74–1.18). The protective effect in the analysis restricted to the epidemic period was not significant: aOR: 0.82 (95% CI; 0.58–1.16). We concluded that prevalence of influenza vaccination was suboptimal. In contrast with most of the available evidence, our results did not support a protective effect of influenza vaccination on the risk of admission for COPD exacerbation.
Air pollution presents a major environmental problem, inducing harmful effects on human health. Particulate matter of 10 μm or less in diameter (PM
) is considered an important risk factor in lung ...carcinogenesis. Epithelial-mesenchymal transition (EMT) is a regulatory program capable of inducing invasion and metastasis in cancer. In this study, we demonstrated that PM
treatment induced phosphorylation of SMAD2/3 and upregulation of SMAD4. We also reported that PM
increased the expression and protein levels of
(TGF-β), as well as EMT markers
(Snail),
(Slug),
(ZEB1),
(N-cadherin),
(α-SMA), and
(vimentin) in the lung A549 cell line. Cell exposed to PM
also showed a decrease in the expression of
(E-cadherin). We also demonstrated that expression levels of these EMT markers were reduced when cells are transfected with small interfering RNAs (siRNAs) against
. Interestingly, phosphorylation of SMAD2/3 and upregulation of SMAD induced by PM
were not affected by transfection of
siRNAs. Finally, cells treated with PM
exhibited an increase in the capacity of invasiveness because of EMT induction. Our results provide new evidence regarding the effect of PM
in EMT and the acquisition of an invasive phenotype, a hallmark necessary for lung cancer progression.
Outdoor particulate matter (PM
) exposure is carcinogenic to humans. The cellular mechanism by which PM
is associated specifically with lung cancer includes oxidative stress and damage to proteins, ...lipids, and DNA in the absence of apoptosis, suggesting that PM
induces cellular survival. We aimed to evaluate the PI3K/AKT/FoxO3a pathway as a mechanism of cell survival in lung epithelial A549 cells exposed to PM
that were subsequently challenged with hydrogen peroxide (H
O
). Our results showed that pre-exposure to PM
followed by H
O
, as a second oxidant stimulus increased the phosphorylation rate of pAKT
, pAKT
, and pFoxO3a
2.5-fold, 1.8-fold, and 1.2-fold, respectively. Levels of catalase and p27
, which are targets of the PIK3/AKT/FoxO3a pathway, decreased 38.1% and 62.7%, respectively. None of these changes had an influence on apoptosis; however, the inhibition of PI3K using the LY294002 compound revealed that the PI3K/AKT/FoxO3a pathway was involved in apoptosis evasion. We conclude that nontoxic PM
exposure predisposes lung epithelial cell cultures to evade apoptosis through the PI3K/AKT/FoxO3a pathway when cells are treated with a second oxidant stimulus.
The effect of tobacco smoking and alcohol drinking on esophageal cancer (EC) has never been explored in Spain where black tobacco and wine consumptions are quite prevalent. We estimated the ...independent effect of different alcoholic beverages and type of tobacco smoking on the risk of EC and its main histological cell type (squamous cell carcinoma) in a hospital-based case-control study in a Mediterranean area of Spain.
We only included incident cases with histologically confirmed EC (n = 202). Controls were frequency-matched to cases by age, sex and province (n = 455). Information on risk factors was elicited by trained interviewers using structured questionnaires. Multiple logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals (CI).
Alcohol drinking and tobacco smoking were strong and independent risk factors for esophageal cancer. Alcohol was a potent risk factor with a clear dose-response relationship, particularly for esophageal squamous-cell cancer. Compared to never-drinkers, the risk for heaviest drinkers (> or = 75 g/day of pure ethanol) was 7.65 (95%CI, 3.16-18.49); and compared with never-smokers, the risk for heaviest smokers (> or = 30 cigarettes/day) was 5.07 (95%CI, 2.06-12.47). A low consumption of only wine and/or beer (1-24 g/d) did not increase the risk whereas a strong positive trend was observed for all types of alcoholic beverages that included any combination of hard liquors with beer and/or wine (p-trend<0.00001). A significant increase in EC risk was only observed for black-tobacco smoking (2.5-fold increase), not for blond tobacco. The effects for alcohol drinking were much stronger when the analysis was limited to the esophageal squamous cell carcinoma (n = 160), whereas a lack of effect for adenocarcinoma was evidenced. Smoking cessation showed a beneficial effect within ten years whereas drinking cessation did not.
Our study shows that the risk of EC, and particularly the squamous cell type, is strongly associated with alcohol drinking. The consumption of any combination of hard liquors seems to be harmful whereas a low consumption of only wine may not. This may relates to the presence of certain antioxidant compounds found in wine but practically lacking in liquors. Tobacco smoking is also a clear risk factor, black more than blond.
Latin-America (LATAM) is the second region in gastric cancer incidence; gastric adenocarcinoma (GA) represents 95% of all cases. We provide a mutational landscape of GA highlighting a) germline ...pathogenic variants associated with hereditary GA, b) germline risk variants associated with sporadic GA, and c) somatic variants present in sporadic GA in LATAM, and analyze how this landscape can be applied for precision medicine. We found that Brazil, Chile, Colombia, Mexico, Peru, and Venezuela are the countries with more published studies from LATAM explicitly related to GA. Our analysis displayed that different germline pathogenic variants for the CDH1 gene have been identified for hereditary GA in Brazilian, Chilean, Colombian, and Mexican populations. An increased risk of developing somatic GA is associated with the following germline risk variants: IL-4, IL-8, TNF-α, PTGS2, NFKB1, RAF1, KRAS and MAPK1 in Brazilian; IL-10 in Chilean; IL-10 in Colombian; EGFR and ERRB2 in Mexican, TCF7L2 and Chr8q24 in Venezuelan population. The path from mutational landscape to precision medicine requires four development levels: 1) Data compilation, 2) Data analysis and integration, 3) Development and approval of clinical approaches, and 4) Population benefits. Generating local genomic information is the initial padlock to overcome to generate and apply precision medicine.
In response to the COVID-19 pandemic, governments declared severe restrictions throughout 2020, presenting an unprecedented scenario of reduced anthropogenic emissions of air pollutants derived ...mainly from traffic sources. To analyze the effect of these restrictions derived from COVID-19 pandemic on air quality levels, relative changes in NO, NO2, O3, PM10 and PM2.5 concentrations were calculated at urban traffic sites in the most populated Spanish cities over different periods with distinct restrictions in 2020. In addition to the changes calculated with respect to the observed air pollutant levels of previous years (2013–2019), relative changes were also calculated using predicted pollutant levels for the different periods over 2020 on a business-as-usual scenario using Multiple Linear Regression (MLR) models with meteorological and seasonal predictors. MLR models were selected among different data mining techniques (MLR, Random Forest (RF), K-Nearest Neighbors (KNN)), based on their higher performance and accuracy obtained from a leave-one-year-out cross-validation scheme using 2013–2019 data. A q-q mapping post-correction was also applied in all cases in order to improve the reliability of the predictions to reproduce the observed distributions and extreme events. This approach allows us to estimate the relative changes in the studied air pollutants only due to COVID-19 restrictions. The results obtained from this approach show a decreasing pattern for NOx, with the largest reduction in the lockdown period above −50%, whereas the increase observed for O3 contrasts with the NOx patterns with a maximum increase of 23.9%. The slight reduction in PM10 (−4.1%) and PM2.5 levels (−2.3%) during lockdown indicates a lower relationship with traffic sources. The developed methodology represents a simple but robust framework for exploratory analysis and intervention detection in air quality studies.
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•COVID-19 lockdown restrictions have derived into a reduction pattern of NOx in 2020.•MLR, RF and KNN are proposed to take into account meteorological variability.•Q-Q Mapping post-correction improves model performance and extreme event prediction.•Smaller changes in air quality were observed from modelled BAU scenario.
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