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Nature Reviews. Clinical Oncology Sep 2023Lung cancer is the leading cause of cancer-related death worldwide. However, lung cancer incidence and mortality rates differ substantially across the world, reflecting... (Review)
Review
Lung cancer is the leading cause of cancer-related death worldwide. However, lung cancer incidence and mortality rates differ substantially across the world, reflecting varying patterns of tobacco smoking, exposure to environmental risk factors and genetics. Tobacco smoking is the leading risk factor for lung cancer. Lung cancer incidence largely reflects trends in smoking patterns, which generally vary by sex and economic development. For this reason, tobacco control campaigns are a central part of global strategies designed to reduce lung cancer mortality. Environmental and occupational lung cancer risk factors, such as unprocessed biomass fuels, asbestos, arsenic and radon, can also contribute to lung cancer incidence in certain parts of the world. Over the past decade, large-cohort clinical studies have established that low-dose CT screening reduces lung cancer mortality, largely owing to increased diagnosis and treatment at earlier disease stages. These data have led to recommendations that individuals with a high risk of lung cancer undergo screening in several economically developed countries and increased implementation of screening worldwide. In this Review, we provide an overview of the global epidemiology of lung cancer. Lung cancer risk factors and global risk reduction efforts are also discussed. Finally, we summarize lung cancer screening policies and their implementation worldwide.
Topics: Humans; Lung Neoplasms; Early Detection of Cancer; Risk Factors; Tobacco Control
PubMed: 37479810
DOI: 10.1038/s41571-023-00798-3 -
Cancers Sep 2023Lung cancer (LC) is the second-most prevalent tumor worldwide. According to the most recent GLOBOCAN data, over 2.2 million LC cases were reported in 2020, with an... (Review)
Review
Lung cancer (LC) is the second-most prevalent tumor worldwide. According to the most recent GLOBOCAN data, over 2.2 million LC cases were reported in 2020, with an estimated new death incident of 1,796,144 lung cancer cases. Genetic, lifestyle, and environmental exposure play an important role as risk factors for LC. E-cigarette, or vaping, products (EVPs) use has been dramatically increasing world-wide. There is growing concern that EVPs consumption may increase the risk of LC because EVPs contain several proven carcinogenic compounds. However, the relationship between EVPs and LC is not well established. E-cigarette contains nicotine derivatives (e.g., nitrosnornicotine, nitrosamine ketone), heavy metals (including organometal compounds), polycyclic aromatic hydrocarbons, and flavorings (aldehydes and complex organics). Several environmental toxicants have been proven to contribute to LC. Proven and plausible environmental carcinogens could be physical (ionizing and non-ionizing radiation), chemicals (such as asbestos, formaldehyde, and dioxins), and heavy metals (such as cobalt, arsenic, cadmium, chromium, and nickel). Air pollution, especially particulate matter (PM) emitted from vehicles and industrial exhausts, is linked with LC. Although extensive environmental exposure prevention policies and smoking reduction strategies have been adopted globally, the dangers remain. Combined, both EVPs and toxic environmental exposures may demonstrate significant synergistic oncogenicity. This review aims to analyze the current publications on the importance of the relationship between EVPs consumption and environmental toxicants in the pathogenesis of LC.
PubMed: 37760496
DOI: 10.3390/cancers15184525 -
International Journal of Molecular... Aug 2023Theories of disease pathogenesis following asbestos exposure have focused on the participation of iron. After exposure, an open network of negatively charged functional... (Review)
Review
Theories of disease pathogenesis following asbestos exposure have focused on the participation of iron. After exposure, an open network of negatively charged functional groups on the fiber surface complexes host metals with a preference for iron. Competition for iron between the host and the asbestos results in a functional metal deficiency. The homeostasis of iron in the host is modified by the cell response, including increased import to correct the loss of the metal to the fiber surface. The biological effects of asbestos develop in response to and are associated with the disruption of iron homeostasis. Cell iron deficiency in the host following fiber exposure activates kinases and transcription factors, which are associated with the release of mediators coordinating both inflammatory and fibrotic responses. Relative to serpentine chrysotile, the clearance of amphiboles is incomplete, resulting in translocation to the mesothelial surface of the pleura. Since the biological effect of asbestos is dependent on retention of the fiber, the sequestration of iron by the surface, and functional iron deficiency in the cell, the greater clearance (i.e., decreased persistence) of chrysotile results in its diminished impact. An inability to clear asbestos from the lower respiratory tract initiates a host process of iron biomineralization (i.e., asbestos body formation). Host cells attempt to mobilize the metal sequestered by the fiber surface by producing superoxide at the phagosome membrane. The subsequent ferrous cation is oxidized and undergoes hydrolysis, creating poorly crystalline iron oxyhydroxide (i.e., ferrihydrite) included in the coat of the asbestos body.
PubMed: 37569765
DOI: 10.3390/ijms241512390 -
Nature Reviews. Clinical Oncology Jan 2024Cancer immunogenomics is an emerging field that bridges genomics and immunology. The establishment of large-scale genomic collaborative efforts along with the... (Review)
Review
Cancer immunogenomics is an emerging field that bridges genomics and immunology. The establishment of large-scale genomic collaborative efforts along with the development of new single-cell transcriptomic techniques and multi-omics approaches have enabled characterization of the mutational and transcriptional profiles of many cancer types and helped to identify clinically actionable alterations as well as predictive and prognostic biomarkers. Researchers have developed computational approaches and machine learning algorithms to accurately obtain clinically useful information from genomic and transcriptomic sequencing data from bulk tissue or single cells and explore tumours and their microenvironment. The rapid growth in sequencing and computational approaches has resulted in the unmet need to understand their true potential and limitations in enabling improvements in the management of patients with cancer who are receiving immunotherapies. In this Review, we describe the computational approaches currently available to analyse bulk tissue and single-cell sequencing data from cancer, stromal and immune cells, as well as how best to select the most appropriate tool to address various clinical questions and, ultimately, improve patient outcomes.
Topics: Humans; Neoplasms; Genomics; Gene Expression Profiling; Transcriptome; Immunotherapy; Tumor Microenvironment
PubMed: 37907723
DOI: 10.1038/s41571-023-00830-6 -
American Journal of Respiratory Cell... Nov 2023Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by progressive lung scarring and remodeling. Although treatments exist that slow...
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by progressive lung scarring and remodeling. Although treatments exist that slow disease progression, IPF is irreversible, and there is no cure. Cellular senescence, a major hallmark of aging, has been implicated in IPF pathogenesis, and mitochondrial dysfunction is increasingly recognized as a driver of senescence. Adenine nucleotide translocases (ANTs) are abundant mitochondrial ATP-ADP transporters critical for regulating cell fate and maintaining mitochondrial function. We sought to determine how alterations in ANTs influence cellular senescence in pulmonary fibrosis. We found that (solute carrier family 25 member 4) (ANT1) and (ANT2) expression is reduced in the lungs of patients with IPF, particularly within alveolar type II (AT2) cells, by single-cell RNA sequencing and tissue staining. Loss of ANT1 by siRNA in lung epithelial cells resulted in increased senescence markers such as β-galactosidase and p21, with a reduction in the ratio of nicotinamide adenine dinucleotide to reduced nicotinamide adenine dinucleotide. Bleomycin-treated ANT1 knockdown cells also had increased senescence markers compared with bleomycin-treated control cells. Loss of ANT1 in AT2 cells resulted in a reduction in alveolar organoid growth, with an increase in p21 by staining. Global loss of ANT1 resulted in worse lung fibrosis and increased senescence in the bleomycin- and asbestos-induced mouse models of pulmonary fibrosis. In summary, loss of ANT1 contributes to IPF pathogenesis through mitochondrial dysfunction, increased senescence, and decreased regenerative capacity of AT2 cells, resulting in enhanced lung fibrosis. Modulation of ANTs presents a new therapeutic avenue that may alter cellular senescence pathways and limit pulmonary fibrosis.
Topics: Animals; Humans; Mice; Bleomycin; Cellular Senescence; Epithelial Cells; Idiopathic Pulmonary Fibrosis; Lung; NAD
PubMed: 37487137
DOI: 10.1165/rcmb.2022-0315OC -
Journal of Occupational and... Oct 2023Asbestos is a mineral that is carcinogenic to humans. Its use has been banned in many occidental countries yet it is still produced in the United States, and materials... (Meta-Analysis)
Meta-Analysis Review
Asbestos is a mineral that is carcinogenic to humans. Its use has been banned in many occidental countries yet it is still produced in the United States, and materials that contain asbestos remain in many occupational settings and indoor environments. Even though asbestos carcinogenicity is well known, there is scant literature on its specific effects regarding small cell lung cancer (SCLC). We therefore conducted a systematic review and meta-analysis to determine SCLC risk among workers exposed to asbestos. A systematic search of the literature was conducted to identify studies which reported occupational exposure to asbestos and SCLC-related deaths and/or incidence. We identified seven case-control studies that included 3,231 SCLC cases; four studies reported smoking-adjusted risks. A significantly increased risk of SCLC (pooled OR 1.89; 95% CI, 1.25-2.86) was observed on pooling studies on men (six studies) that displayed moderate heterogeneity (I = 46.0%). Overall, our synthesis suggests that occupational exposure to asbestos significantly increases the risk of SCLC on men.
Topics: Male; Humans; United States; Small Cell Lung Carcinoma; Lung Neoplasms; Asbestos; Occupational Exposure; Carcinogens; Occupational Diseases
PubMed: 37405865
DOI: 10.1080/15459624.2023.2232421