Lung Cancer In Nonsmokers Research Articles

Non-Invasive Detection of Lung Cancer: Integrating Genomic Data with Ensemble Learning for Improved Early Diagnosis

The early and accurate diagnosis of lung cancer, a significant contributor to global cancer-related mortality, remains a paramount challenge in healthcare. Conventional diagnostic methods often lack the sensitivity required for early-stage detection, prompting the exploration of non-invasive alternatives. Leveraging advancements in genomics and bioinformatics, this study investigates the potential of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) analysis for early-stage lung cancer diagnosis. Two distinct datasets are utilized: GSE4115, comprising gene expression data from bronchial airway epithelial cells of smokers, and GSE33356, focusing on genomic alterations in Taiwanese female non-smoking lung cancer patients. The research employs comprehensive data pre-processing and feature reduction techniques, including normalization and Kernel Principal Component Analysis (KPCA). Subsequently, an ensemble of diverse learners, including Random Forests, AdaBoost, Bagging, Support Vector Machines (SVMs), and Neural Networks, is trained on the original datasets. A novel ensemble stacking approach is proposed, wherein initial predictions from the base learners are combined through logistic regression - the meta-learner to enhance predictive performance. The study aims to contribute to advancements in lung cancer detection by providing a more precise and non-invasive diagnostic method. By integrating DNA and RNA analysis with ensemble learning techniques, the research endeavours to enhance medical outcomes and potentially save lives through early-stage lung cancer detection.

The role of PM2.5 exposure in lung cancer: mechanisms, genetic factors, and clinical implications.

Lung cancer is one of the most critical global health threats, as the second most common cancer and leading cause of cancer deaths globally. While smoking is the primary risk factor, an increasing number of cases occur in nonsmokers, with lung cancer in nonsmokers (LCNS) now recognized as the fifth leading cause of cancer mortality worldwide. Recent evidence identifies air pollution, particularly fine particulate matter (PM2.5), as a significant risk factor in LCNS. PM2.5 can increase oxidative stress and inflammation, induce genetic alterations and activation of oncogenes (including the epidermal growth factor receptor, EGFR), and contribute to lung cancer progression. This review summarizes the current understanding of how exposure to PM2.5 induces lung carcinogenesis and accelerates lung cancer development. It underscores the importance of prevention and early detection while calling for targeted therapies to combat the detrimental effects of air pollution. An integrated approach that combines research, public health policy, and clinical practice is essential to reduce the lung cancer burden and improve outcomes for those affected by PM2.5 exposurrre.

Molecular Compositions, Mutagenicity, and Mutation Spectra of Atmospheric Oxidation Products of Alkenes and Dienes Initiated by NOx + UV or Ozone: A Structure-Activity Analysis.

Photooxidation products resulting from volatile organic compounds (VOCs) reacting with sunlight are important contributors to gas-phase air pollution. We characterized the product-weighted mutagenic potencies (rev m3 mgC-1 h-1) in Salmonella TA100 of atmospheres resulting from the hydroxyl radical (OH)-initiated photochemical oxidation of 11 C4 or C5 alkenes or dienes in the presence of nitric oxide (NO) and from the ozonolysis of four VOCs without NO (isoprene; 1,3-pentadiene; 1,4-pentadiene; and 1,3-butadiene). Irradiated atmospheres from precursors with a single C═C bond (3-methyl-1-butene, 2-methyl-1-butene, cis/trans-2-pentene, 2-methyl-2-butene, 1-butene, and 1-pentene) had low potencies (<5), whereas linear dienes with terminal C═C bonds had high potencies (50-65). Dienes with a branched structure (isoprene) or internal C═C bonds (1,3-pentadiene) had intermediate potencies (15-20). No VOCs were mutagenic without photochemical oxidation. VOCs+O3 in the dark produced less mutagenic atmospheres than photochemistry in the presence of NO. Atmospheres induced primarily C to T and C to A mutations, the main base substitutions in nonsmoker lung cancer. Atmospheres from the photooxidation of isoprene and 1,3-pentadiene also induced GG to TT, the signature mutation of peroxyacetyl nitrate. Five molecular compositions identified by Chemical Ionization Mass Spectrometry (CIMS), most containing nitrogen, correlated (r = 0.76-0.85) with the mutagenic potencies of irradiated atmospheres; most had a likely nitrate functional group. Assessment of the mutagenicity of emitted VOCs should consider VOC photooxidation products, especially dienes with terminal C═C bonds, as these products likely contribute to overall health effects from ambient air pollution.

Re-visiting the association between antidepressant use and the risk of lung cancer.

Observational studies suggest a potential correlation between antidepressants and increased lung cancer risks. However, existing studies are limited to small sample sizes, unadjusted covariates especially smoking status, and unclear exposure duration. We performed a large-scale retrospective cohort study to re-examine the association. We analyzed non-smokers and smokers separately to eliminate the confounding effect of smoking status. We found patients with long-term antidepressant use were at a lower risk of lung cancer in both smokers and non-smokers (odds ratio (OR), 0.61; 95% CI: 0.46-0.80, OR: 0.75; 95% CI: 0.65-0.86). None of the antidepressants was associated with an increased lung cancer risk.

Emerging Epidemic: Non-Smoker Lung Cancer in India\'s Urban Centres

Abstract: Recent research has revealed a concerning trend in the incidence of lung cancer among non-smokers in India, particularly within urban centers. Contrary to the traditional association of lung cancer with smoking, a significant proportion of cases in India are now emerging in individuals with no history of tobacco use. This phenomenon is primarily attributed to severe air pollution, which has become a critical public health issue in many Indian cities. Rapid industrialization and urbanization have led to increased exposure to airborne pollutants, including fine particulate matter (PM2.5), nitrogen dioxide (NO2), and other carcinogens, which are now recognized as significant risk factors for lung cancer. Genetic predispositions further exacerbate this risk, with studies indicating that certain populations are more susceptible to developing lung cancer due to genetic mutations influenced by environmental exposures. These mutations and biomarkers, such as EGFR and ALK gene rearrangements, have been increasingly identified in Indian non-smoker lung cancer patients, providing critical insights into the disease's etiology and potential targeted therapies. India currently ranks fourth globally in lung cancer prevalence, with urban areas experiencing the highest growth rates. Projections suggest that the incidence of lung cancer will continue to rise, potentially reaching alarming levels by 2025. This emerging epidemic highlights the urgent need for comprehensive public health strategies to address air pollution and its associated health risks. Efforts must be directed towards reducing pollution levels through stringent regulatory measures, promoting cleaner technologies, and enhancing public awareness about the health impacts of air pollution. Additionally, implementing widespread screening programs and advancing research on genetic and environmental interactions can aid in early detection and personalized treatment approaches for affected individuals. In conclusion, the rising incidence of lung cancer among non-smokers in urban India signifies a shifting landscape in the disease's epidemiology. Addressing this public health challenge requires an integrated approach that combines environmental, genetic, and healthcare interventions to mitigate the growing burden of lung cancer in non-smoking populations.

The Personalized Inherited Signature Predisposing to Non-Small-Cell Lung Cancer in Non-Smokers.

Lung cancer (LC) continues to be an important public health problem, being the most common form of cancer and a major cause of cancer deaths worldwide. Despite the great bulk of research to identify genetic susceptibility genes by genome-wide association studies, only few loci associated to nicotine dependence have been consistently replicated. Our previously published study in few phenotypically discordant sib-pairs identified a combination of germline truncating mutations in known cancer susceptibility genes in never-smoker early-onset LC patients, which does not present in their healthy sib. These results firstly demonstrated the presence of an oligogenic combination of disrupted cancer-predisposing genes in non-smokers patients, giving experimental support to a model of a "private genetic epidemiology". Here, we used a combination of whole-exome and RNA sequencing coupled with a discordant sib's model in a novel cohort of pairs of never-smokers early-onset LC patients and in their healthy sibs used as controls. We selected rare germline variants predicted as deleterious by CADD and SVM bioinformatics tools and absent in the healthy sib. Overall, we identified an average of 200 variants per patient, about 10 of which in cancer-predisposing genes. In most of them, RNA sequencing data reinforced the pathogenic role of the identified variants showing: (i) downregulation in LC tissue (indicating a "second hit" in tumor suppressor genes); (ii) upregulation in cancer tissue (likely oncogene); and (iii) downregulation in both normal and cancer tissue (indicating transcript instability). The combination of the two techniques demonstrates that each patient has an average of six (with a range from four to eight) private mutations with a functional effect in tumor-predisposing genes. The presence of a unique combination of disrupting events in the affected subjects may explain the absence of the familial clustering of non-small-cell lung cancer. In conclusion, these findings indicate that each patient has his/her own "predisposing signature" to cancer development and suggest the use of personalized therapeutic strategies in lung cancer.

222Rn and 220Rn levels in drinking water, emanation, and exhalation assessment, and the related health implications in the U-bearing area of Poli-Cameroon.

The inherent radioactivity of radon gas presents potential exposure risks to human beings through ingestion and inhalation of its radioisotopes 222Rn (radon) and 220Rn (thoron) from water sources. Recent studies have been conducted to assess radon concentrations in different environmental matrices such as water, air, and soil, due to their detrimental impact on human health. As the main cause of lung cancer in non-smokers and an acknowledged contributor to stomach cancer when ingested, the present study aimed to preliminarily assess radon and thoron levels in the Uranium bearing area of Poli in the Faro division of Cameroon, known for its significant U-deposits. The assessment included measuring 220, 222Rn concentrations in drinking water, emanation, and exhalation, with a specific focus on evaluating the exposure of different age groups within the local population. The radon/thoron levels in water and their related exposure and cancer risk dataindicated no immediate health hazards. However, continuous monitoring and prospective measures are deemed essential due to the area's abundant U-minerals. The emanation measurements showed sparsely distributed data with a singularity at Salaki, where the equipment recorded values of 8.14 × 1012 Bqm-3 and 3.27 × 1012 Bqm-3 for radon and thoron, respectively. Moreover, radon/thoron transfer coefficients from thesoil to theair indicated levels below unity. While the calculated doses suggest minimum potential risk in line with WHO and UNSCEAR guidelines, the obtained results are expected to significantly contribute to the establishment of national standards for radon levels in drinking water, emanation, and exhalation. Furthermore, these findings can play a crucial role in monitoring radon/thoron levels to ensure public health safety.

Urinary Metabolite Diagnostic and Prognostic Liquid Biopsy Biomarkers of Lung Cancer in Nonsmokers and Tobacco Smokers.

Nonsmokers account for 10% to 13% of all lung cancer cases in the United States. Etiology is attributed to multiple risk factors including exposure to secondhand smoking, asbestos, environmental pollution, and radon, but these exposures are not within the current eligibility criteria for early lung cancer screening by low-dose CT (LDCT). Urine samples were collected from two independent cohorts comprising 846 participants (exploratory cohort) and 505 participants (validation cohort). The cancer urinary biomarkers, creatine riboside (CR) and N-acetylneuraminic acid (NANA), were analyzed and quantified using liquid chromatography-mass spectrometry to determine if nonsmoker cases can be distinguished from sex and age-matched controls in comparison with tobacco smoker cases and controls, potentially leading to more precise eligibility criteria for LDCT screening. Urinary levels of CR and NANA were significantly higher and comparable in nonsmokers and tobacco smoker cases than population controls in both cohorts. Receiver operating characteristic analysis for combined CR and NANA levels in nonsmokers of the exploratory cohort resulted in better predictive performance with the AUC of 0.94, whereas the validation cohort nonsmokers had an AUC of 0.80. Kaplan-Meier survival curves showed that high levels of CR and NANA were associated with increased cancer-specific death in nonsmokers as well as tobacco smoker cases in both cohorts. Measuring CR and NANA in urine liquid biopsies could identify nonsmokers at high risk for lung cancer as candidates for LDCT screening and warrant prospective studies of these biomarkers.

Abstract 859: Development of non-smoking lung cancers by indoor carcinogenic aerosols through epigenetic reprogramming of lung stem cells: Bioinformatics and artificial intelligence analysis

Abstract Several scientific studies discovered the toxic effects of indoor aerosols on different organs’ adult stem cells of the human body. The most importantly, the indoor toxic aerosols comprised of numerous carcinogens namely, sodium dodecyl sulfate, phthalic acids from floor cleaners, formaldehyde, acetaldehyde, benzene, toluene, ethyl benzene, xylenes, from air fresheners, Hydramethylnon, Pyrethrins, imiprothrin, cypermethrin, tetramethrin, prallethrin and permethrin from ant and roach Killer. However, there was a lack of analysis revealing the mechanism of toxic effects and epigenetic reprogramming of human lung stem cells and development of non-smoking lung cancers. In this study, we analyzed the toxic effects of these chemicals and the mechanism of epigenetic reprograming on lung epithelial cells using Comparative Toxico-genomics Database (CTD), database of Environmental Health Perspectives (EHP), National Institute of Environmental Health Sciences (NIEHS), Google search browser with generative artificial intelligence (AI) and other biological informatics methods (Reactome, Cytoscape PSICQUIC services, and ChEMBL database). We observed from CTD analysis that the chemical gene interactions as risk factors from indoor aerosols showed transcriptionally highly expressed of 31 common genes, by phthalic acids, sodium dodecyl sulfate, from the total of 1347 genes, 107 common genes by formaldehyde, acetaldehyde from the total of 4193 genes and all other toxic ingredients of indoor aerosols. The epigenetic mechanism of histone modifications (H3K4me3, H3K9me3, H3K27me3, H3K27ac, H3K36me3, H3K4me1, Hsa-mir-1301 of lung epithelial, and miRNAs have been revealed by NIH Roadmap Epigenomics Mapping Consortium and the lung tissue arrays were analyzed with AI and matplotlib program. The heterogenic adult stem cell reprogramming is regulated by epigenetic bivalent histone modifications at transcript starts sequences (TSS) of target genes and our current study revealed that CD44, CD80, ALDH2, ALDH3A1, ALDH3B2 are epigenetically reprogrammed with close interaction of other genes by these toxic ingredients of indoor aerosols. Therefore, our results are significant for the carcinogenic effects of indoor aerosols causing for development of lung cancer epigenetically, which may give a clue for the prevention and treatment of nonsmoking lung cancer. Citation Format: Juan Anderson, Mariah Delgado, Malcolm Lovett, Maya Saunders, Geovannie Lake, Samuel Darko, Rose M. Stiffin, Ayivi Huisso, Marilyn Sherman, Latoya Appleton, Amalya Mihnea, Swarnava Das, Mohammad M. Algahtani, Ravi Vadapalli, Biswarup Basu, Arunima Biswas, Noor Neha, Madhumita Das, Marco A. Ruiz, Mayur Doke, Jayanta K. Das. Development of non-smoking lung cancers by indoor carcinogenic aerosols through epigenetic reprogramming of lung stem cells: Bioinformatics and artificial intelligence analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 859.

Evaluation of Risk Factors for Lung Cancer Among Never Smokers and Their Association With Common Driver Mutations.

The majority of lung cancers are caused by tobacco use, which is linked to lung tumors of all major histological types. A considerable fraction of lung cancer cases, the vast majority of which are adenocarcinomas, occur in "never smokers," who are characterized as having smoked fewer than 100 cigarettes in their lives. The primary objective was to assess risk factors for lung cancer in non-smokers. In contrast, secondary objectives included evaluating histological subtype, staging, and performance status and exploring associations between risk factors and common driver mutations. The study was a single-center, observational, case-control study done at All India Institute of Medical Science, Bhubaneswar, Indiathat focused on non-smokers with lung cancer. It included 145 cases and 297 controls, with statistical analyses such as chi-square tests and logistic regression used to assess associations between risk factors and lung cancer, considering factors such as socioeconomic status, body mass index (BMI), occupation, outdoor and indoor air pollution, personal habits, and medical history. The study, comprising 145 lung cancer cases in non-smokers and 297 controls, found that 92.4% (134/145) of cases had adenocarcinoma, 6.9% (10/145) had squamous cell carcinoma, and 0.7% (1/145) had small cell carcinoma. Significant associations were observed for high-risk occupations, indoor biomass use without proper ventilation, low BMI, and family history of lung cancer. Specific pre-existing lung conditions like old pulmonary tuberculosis and asthma were linked to increased and decreased odds of developing lung cancer, respectively. Environmental factors, living near heavy industry, and dietary habits showed significant associations. A significant association was not found between the driver mutations and the risk factors studied. This single-center study sheds light on significant risk factors influencing lung cancer development among non-smokers. The predominant occurrence of adenocarcinoma and associations with high-risk occupations, indoor biomass exposure, low BMI, and family history emphasize the multifaceted nature of non-smoking-related lung cancer. The findings underscore the importance of comprehensive risk assessment and targeted preventive strategies in this population.

The interplay between autophagy and apoptosis: its implication in lung cancer and therapeutics

Maintaining cellular homeostasis relies on the interplay between apoptosis and autophagy, and disruption in either of these processes can contribute to the development of cancer. Autophagy can hinder the apoptotic process, and when autophagy is inhibited in such instances, it can enhance the rate of apoptosis. However, evidence suggests that excessive autophagy can also lead to apoptotic cell death. Also, excess autophagy can cause excessive digestion of cellular organelles, causing autophagic cell death. Targeting autophagy in non-small cell lung cancer (NSCLC), the most common form of lung cancer, can be very tricky due to the dual nature of autophagy. According to genetic analysis, various mutations in p53 and EGFR, G:C to A:T transversions seem responsible for the development of lung cancer in smokers and non-smokers. These events trigger cytoprotective autophagy or induce apoptotic cell death through different but interconnected signalling pathways. Lung cancer being the leading cause of death worldwide, calls for more attention to disease prognosis and new therapeutics in the market. However, molecules responsible for autophagy to apoptosis transition are yet to be studied elaborately. Also, the role of effector caspases during this shift needs to be elucidated in future. To comprehend how therapeutics operate through the modulation of autophagy and apoptosis and to target such pathways, it is crucial to emphasize these intricate connections. Many therapeutics discussed in this review targeting both apoptosis and autophagy have shown promising results in vitro and in vivo, however, few have crossed the hurdles of clinical trial. Nevertheless, the quest for safer and better efficacious agents is still alive, with the sole aim to develop novel cancer chemotherapeutic(s).

How to spot the signs of non-smoking lung cancer

How to spot the signs of non-smoking lung cancer

Comprehensive analysis of clinical, radiological, pathological findings, and survival outcomes in non-smoker non-small cell lung cancer patients

Comprehensive analysis of clinical, radiological, pathological findings, and survival outcomes in non-smoker non-small cell lung cancer patients

A Canadian First Nations radon assessment and COVID-19 restrictions: A difficult pairing

Radon is a known carcinogen and a by-product of degrading naturally occurring radioactive elements. The North Shore Micmac District Council (NSMDC) board of directors, in Eastern New Brunswick, Canada, were aware of this issue and saw a need for increased radon testing and awareness in their communities. The initial plan was to administer a testing blitz across communities to gauge the current levels of radon exposure in both residential and band-owned structures. This, with Elder consultation and a participant health survey, would create a data set used to guide future strategies effectively and better direct resources to mitigate the leading cause of lung cancer in non-smokers. These plans were put in place prior to the COVID-19 pandemic that began in March 2020. The subsequent provincial levels of restriction could not have been predicted. The ever-changing pandemic-related restrictions, and public health’s focus on a new deadly pathogen, led to difficulties managing and following through on many health and wellness projects. These circumstances led to a unique situation that delayed results, prolonged exposure to a known carcinogen, and may have consequences in the long term. Few procedures, treatments, or medications do not have side effects, and even warranted pandemic-related measures affect other aspects of health.

Supporting diagnosis of non-smoking lung cancer

Supporting diagnosis of non-smoking lung cancer

Immune status of people living in the Tande-Tande sub-village (Indonesia), an area with high indoor radon concentration.

On Earth, there are significant variations in terms of exposure to naturally occurring radiation among different areas. Radon, a naturally-occurring radioactive gas that is the primary cause of lung cancer in nonsmokers and the second most prevalent cause among smokers, poses a considerable risk. Indoor radon, in particular, constitutes the most substantial source of natural radiation to which individuals are exposed. This study assessed the immune status of a population chronically exposed to high indoor radon concentration in Indonesia. Fifty-seven subjects from the Tande-Tande sub-village (high indoor radon concentration area) were compared to fifty-three participants living in the Topoyo village (low concentration area). We contrasted the immunological conditions of these two populations by measuring levels of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-4 (IL-4), and IL-10 in serum. Moreover, we also measured levels of the nuclear factor kappa B (NF-κB), superoxide dismutase (SOD), glutathione peroxidase (GPX), and protein kinase B in its phosphorylated (pAkt) and non-phosphorylated form (Akt) in peripheral blood mononuclear cells (PBMCs) of a subset of participants (31 from each population). TNF-α, IFN-γ, and IL-4 levels in Tande-Tande sub-village inhabitants were significantly lower than those in the control group living in the Topoyo village (p = 0.001, p = 0.017, and p = 0.002). The concentration of IL-10 also tended to be lower in people living in the high indoor radon concentration area, but it did not differ significantly between Tande-Tande sub-village inhabitants and Topoyo inhabitants (p = 0.106). Protein levels of NF-κB, pAkt, and Akt in Tande-Tande sub-village inhabitants also did not differ significantly between Tande-Tande sub-village inhabitants and Topoyo inhabitants (p = 0.234, p = 0.210, and p = 0.657). Similarly, activities of SOD and GPX did not differ significantly between the two populations (p = 0.569 and p = 0.949). Overall, despite their chronic exposure to high indoor radon concentrations, our study revealed no increase in the levels of TNF-α, IFN-γ, IL-10, IL-4, SOD, and GPX in the inhabitants of Tande-Tande sub-village compared with people living in the Topoyo village. Furthermore, our study demonstrated no activation in the Akt pathway, as indicated by the pAkt/Akt ratio observed in PBMC lysates of individuals residing in the Tande-Tande sub-village.

Applying machine learning to model radon using topsoil geochemistry

Radon is classified as a Class 1 carcinogen, being the leading cause of lung cancer in non-smokers. Understanding the prominent sources of radon helps to mitigate against the adverse effects of radon exposure. Considering soil-gas radon is the main contributor to indoor radon, it is possible that soil geochemistry can be used as a proxy for the soil radon emanation potential or geogenic radon classes for a particular location. This paper investigates the relationship between soil geochemistry and geogenic radon. A large area of 17,983 km2 from the West, Midlands and East of Ireland was selected to represent a range of geology types and radon categories. A rigorous assessment is presented to investigate the relationship of geogenic radon and topsoil geochemistry; using univariate processes (i.e. r2, Pearson r and heatmaps) and multivariate techniques (i.e. principle component analysis (PCA) and machine learning (ML) algorithms including Gaussian process regression, logistic regression and random forest). Here, PCA and ML techniques were used to test the utility of soil geochemistry to predict geogenic radon classes. Gaussian Process Regression yielded the highest accuracy (74%) and f1-score (0.74) of all models. The feature importance (i.e. highest ranking elements for predicting geogenic radon class) from the ML models outputs elements including [Y, Tl, Mn, Cr, Co, Be, Sc and Rb]. The PCA biplot demonstrates that these elements cluster in conjunction with higher geogenic radon categories. Multivariate data analysis reveals that certain elements important for predicting higher geogenic radon classes, also covary together within topsoil samples; here these are termed “radon-prone elements”. Spatial covariance of radon-prone elements permits soil geochemistry to be used as a tool for understanding the distribution of geogenic radon. The methodology presented in this paper provides a comprehensive geo-statistical approach to investigate the relation between topsoil geochemistry and geogenic radon. This approach could be applied as a diagnostic tool to assist radon mitigation measures, hence adding value to legacy soil geochemistry datasets.

Ethnic differences of genetic risk and smoking in lung cancer: two prospective cohort studies.

The role of genetic background underlying the disparity of relative risk of smoking and lung cancer between European populations and East Asians remains unclear. To assess the role of ethnic differences in genetic factors associated with smoking-related risk of lung cancer, we first constructed ethnic-specific polygenic risk scores (PRSs) to quantify individual genetic risk of lung cancer in Chinese and European populations. Then, we compared genetic risk and smoking as well as their interactions on lung cancer between two cohorts, including the China Kadoorie Biobank (CKB) and the UK Biobank (UKB). We also evaluated the absolute risk reduction over a 5-year period. Differences in compositions and association effects were observed between the Chinese-specific PRSs and European-specific PRSs, especially for smoking-related loci. The PRSs were consistently associated with lung cancer risk, but stronger associations were observed in smokers of the UKB [hazard ratio (HR) 1.26 vs 1.15, P = 0.028]. A significant interaction between genetic risk and smoking on lung cancer was observed in the UKB (RERI, 11.39 (95% CI, 7.01-17.94)], but not in the CKB. Obvious higher absolute risk was observed in nonsmokers of the CKB, and a greater absolute risk reduction was found in the UKB (10.95 vs 7.12 per 1000 person-years, P <0.001) by comparing heavy smokers with nonsmokers, especially for those at high genetic risk. Ethnic differences in genetic factors and the high incidence of lung cancer in nonsmokers of East Asian ethnicity were involved in the disparity of smoking-related risk of lung cancer.

Changing profile of lung cancer clinical characteristics in China: Over 8-year population-based study.

Although examinations and therapies for bronchial lung cancer, also called lung cancer (LC), have become more effective and precise, the morbidity and mortality of LC remain high worldwide. Describing the changing profile of LC characteristics over time is indispensable. This study aimed to understand the changes in real-world settings of LC and its characteristics in China. In this study, 119,785 patients were enrolled from 2012 to 2020 in the Shanghai Pulmonary Hospital. The patients' medical records were extracted from the hospital's database. Demographic characteristics, general clinicopathological information, and blood coagulation indices at the initial diagnoses were analyzed using the Kruskal-Wallis, Nemenyi, chi-squared, and Bonferroni tests. Changes in demographic characteristics during the 8-year study period, namely dynamic changes among different stages and different pathological types, were evaluated. The percentages of female (from 38.50% [323/839] in 2012 to 48.29% [5112/10,585] in 2020) and non-smoking LC (from 69.34% [475/685] to 80.48% [8055/10,009]) patients increased significantly during the study period, with a trend toward a younger age at diagnosis (from 3.58% [30/839] to 8.99% [952/10,585]). Over the study period, the proportion and absolute number of lung adenocarcinoma cases increased (from 67.97% [433/637] to 76.31% [6606/8657]) while the proportion of lung squamous cell carcinoma decreased (from 21.19% [135/637] to 12.08% [1046/8657]). Comprehensive driver gene mutation examination became more common, and epidermal growth factor receptor (EGFR) mutation occurred more frequently in female vs. male (62.03% [12793/20625] vs. 29.90% [8207/27,447]) and non-smoking vs. smoking (53.54% [17,203/32,134] vs. 23.73% [3322/13,997]) patients (both P<0.001). The distribution of the common driver genes differed among different stages of LC. EGFR mutation was detected most frequently at each stage, and other driver gene alterations were more common in advanced stages (P<0.001). The combination of chemotherapy, targeted therapy, and immunotherapy, as a comprehensive management regimen, gradually became predominant over the study period (P<0.001). A hypercoagulable state was shown in advanced-stage LC patients and patients with the anaplastic lymphoma kinase fusion, indicated by significantly elevated levels of d-dimer, fibrinogen, and fibrinogen degradation products. This study comprehensively depicted the changing characteristics of Chinese LC patients over an 8-year period to provide preliminary insights into LC treatment.Trial registration: ClinicalTrials.gov, NCT05423236.

Lung cancer in nonsmokers- A risk factor analysis

Institutions:stony brook medical centerrationaleLung Cancer screening for the high-risk smoking population has been proven to save lives. However, in 2022, 20% of newly diagnosed lung cancers (47,300) were in nonsmokers. These patients were found to be diagnosed at later stages. This may be at least partly due to not meeting criteria for and participating in current lung cancer screening. This study aims to describe characteristics of a never smoker patient population to help identify common risk factors which might merit inclusion in lung cancer screening and thus improve patient outcomes. MethodsThis retrospective single center study included never-smoker patients diagnosed with lung nodules and never-smoker patients diagnosed with lung cancer from 2016 to 2022. Data was obtained from the Stony Brook Medical Center electronic medical record. 16,056 patients were identified as never-smokers who were asked by the medical assistant if they ever smoked in their lifetime. Patients were eliminated if they had any smoking history up to first diagnosis date. Demographics, radiology, histology, diagnosis dates, comorbidities, smoking status, and exposures collected through ICD10 codes and not self-reported, were investigated. ResultsOf 16,056 never-smoking patients, 9315 (58.02%) were females diagnosed with lung nodules and 6741 (41.98%) were males diagnosed with lung nodules.The univariate analysis showed significant differences between gender, age at nodule diagnosis, and patients with and without comorbidities including chronic obstructive pulmonary disease (COPD), hypertension (HTN), and family history (FHX) of lung cancer. The percentage of lung cancer patients among females was significantly higher than among males. Patients having lung cancer were older. The percentages of lung cancer patients with these comorbidities were significantly higher than those without. However, there was no significant difference found between patients with and without diabetes mellitus (DM).The multivariable logistic regression suggested that age at nodule diagnosis and comorbidities including COPD (which included asthma, emphysema and chronic bronchitis) and family history of lung cancer were significantly associated with lung cancer. Older patients and patients with those comorbidities had a higher risk of developing cancer than those who were younger or without those comorbidities. The study excluded HTN and included age at nodule diagnosis in the logistic regression model as HTN was found to be protective against lung cancer due to age at lung nodule diagnosis. Please refer to the appendix for further details. ConclusionNever-smoker patients who were older and with COPD and Family History of lung cancer had higher risk of developing lung cancer than younger patients without these comorbidities. In this study, gender had no impact on outcome.