Beyond tobacco: genomic disparities in lung cancer between smokers and never-smokers.

BACKGROUND: Tobacco use is one of the main risk factors for Lung Cancer (LC) development. However, about 10-20% of those diagnosed with the disease are never-smokers. For Non-Small Cell Lung Cancer (NSCLC) there are clear differences in both the clinical presentation and the tumor genomic profiles between smokers and never-smokers. For example, the Lung Adenocarcinoma (LUAD) histological subtype in never-smokers is predominately found in young women of European, North American, and Asian descent. While the clinical presentation and tumor genomic profiles of smokers have been widely examined, never-smokers are usually underrepresented, especially those of a Latin American (LA) background. In this work, we characterize, for the first time, the difference in the genomic profiles between smokers and never-smokers LC patients from Chile. METHODS: We conduct a comparison by smoking status in the frequencies of genomic alterations (GAs) including somatic mutations and structural variants (fusions) in a total of 10 clinically relevant genes, including the eight most common actionable genes for LC (EGFR, KRAS, ALK, MET, BRAF, RET, ERBB2, and ROS1) and two established driver genes for malignancies other than LC (PIK3CA and MAP2K1). Study participants were grouped as either smokers (current and former, n = 473) or never-smokers (n = 200) according to self-report tobacco use at enrollment. RESULTS: Our findings indicate a higher overall GA frequency for never-smokers compared to smokers (58 vs. 45.7, p-value < 0.01) with the genes EGFR, KRAS, and PIK3CA displaying the highest prevalence while ERBB2, RET, and ROS1 the lowest. Never-smokers present higher frequencies in seven out of the 10 genes; however, smokers harbor a more complex genomic profile. The clearest differences between groups are seen for EGFR (15.6 vs. 21.5, p-value: < 0.01), PIK3CA (6.8 vs 9.5) and ALK (3.2 vs 7.5) in favor of never-smokers, and KRAS (16.3 vs. 11.5) and MAP2K1 (6.6 vs. 3.5) in favor of smokers. Alterations in these genes are comprised almost exclusively by somatic mutations in EGFR and mainly by fusions in ALK, and only by mutations in PIK3CA, KRAS and MAP2K1. CONCLUSIONS: We found clear differences in the genomic landscape by smoking status in LUAD patients from Chile, with potential implications for clinical management in these limited-resource settings.

Distribution of Solid Lung Nodules Presence and Size by Age and Sex in a Northern European Nonsmoking Population.

Background Most of the data regarding prevalence and size distribution of solid lung nodules originates from lung cancer screening studies that target high-risk populations or from Asian general cohorts. In recent years, the identification of lung nodules in non-high-risk populations, scanned for clinical indications, has increased. However, little is known about the presence of solid lung nodules in the Northern European nonsmoking population. Purpose To study the prevalence and size distribution of solid lung nodules by age and sex in a nonsmoking population. Materials and Methods Participants included nonsmokers (never or former smokers) from the population-based Imaging in Lifelines study conducted in the Northern Netherlands. Participants (age ≥ 45 years) with completed lung function tests underwent chest low-dose CT scans. Seven trained readers registered the presence and size of solid lung nodules measuring 30 mm3 or greater using semiautomated software. The prevalence and size of lung nodules (≥30 mm3), clinically relevant lung nodules (≥100 mm3), and actionable nodules (≥300 mm3) are presented by 5-year categories and by sex. Results A total of 10 431 participants (median age, 60.4 years [IQR, 53.8-70.8 years]; 56.6% [n = 5908] female participants; 46.1% [n = 4812] never smokers and 53.9% [n = 5619] former smokers) were included. Of these, 42.0% (n = 4377) had at least one lung nodule (male participants, 47.5% [2149 of 4523]; female participants, 37.7% [2228 of 5908]). The prevalence of lung nodules increased from age 45-49.9 years (male participants, 39.4% [219 of 556]; female participants, 27.7% [236 of 851]) to age 80 years or older (male participants, 60.7% [246 of 405]; female participants, 50.9% [163 of 320]). Clinically relevant lung nodules were present in 11.1% (1155 of 10 431) of participants, with prevalence increasing with age (male participants, 8.5%-24.4%; female participants, 3.7%-15.6%), whereas actionable nodules were present in 1.1%-6.4% of male participants and 0.6%-4.9% of female participants. Conclusion Lung nodules were present in a substantial proportion of all age groups in the Northern European nonsmoking population, with slightly higher prevalence for male participants than female participants. © RSNA, 2024 Supplemental material is available for this article.

Dietary Patterns among Smokers and Non-Smokers: Findings from the National Health and Nutritional Examination Survey (NHANES) 2017-2018.

Diet behavior and nutrition are critical for maintaining health and improving quality of life. Cigarette smoking remains the leading cause of preventable death in the United States. Poor dietary choices, such as excessively frequenting restaurants, consuming ready-to-eat foods from grocery stores, and ingesting ultra-processed foods (like frozen meals and pizzas), can adversely impact health. Despite this, research comparing dietary behaviors between smokers and non-smokers is limited. Using data from the National Health and Nutritional Examination Survey 2017-2018, we analyzed diet behavior based on smoking status. Our findings reveal that smokers had a significant increase (90%) in the frequency of consuming frozen meals/pizzas in the past 30 days compared to non-smokers (coefficient: 1.9; 95% CI: 1.4, 2.6; p-value < 0.001). Additionally, over 70% of participants, regardless of their smoking status, were unaware of MyPlate, a nutritional guide created by the United States Department of Agriculture (USDA) to encourage Americans to make healthier food choices. There is an urgent need to increase public awareness of MyPlate and promote a better understanding of healthy dietary behaviors.

Sex difference in the associations among secondhand smoke with metabolic syndrome in non-smokers in a large Taiwanese population follow-up study.

Close associations among secondhand smoke (SHS) and metabolic syndrome (MetS) and its components have been demonstrated, however sex differences in these associations remain unclear. We collected 121,364 participants from the Taiwan Biobank, and excluded those with smoking history, the remaining 88,297 participants (male: 18,595; female: 69,702; mean age 50.1 ± 11.0 years) were included. SHS exposure was evaluated based on self-reported questionnaires. SHS was associated with MetS (odds ratio [OR], 1.268, p < 0.001 for males vs. 1.180, p < 0.001 for females), abdominal obesity (OR, 1.234, p < 0.001 for males vs. 1.199, p < 0.001 for females), low high-density lipoprotein cholesterol (OR, 1.183, p = 0.008 for males vs. 1.094, p = 0.011 for females), hyperglycemia (OR, 1.286, p < 0.001 for males vs. 1.234, p < 0.001 for females), but not with hypertriglyceridemia. SHS was associated with high blood pressure (BP) (OR, 1.278, p < 0.001) only in males, but not in females. Furthermore, significant interactions were found between sex x SHS on MetS (p = 0.023), abdominal obesity (p = 0.032), and elevated BP (p < 0.001). Moreover, the participants who were exposed to SHS for ≥1 hour per week were associated with a higher risk (OR = 1.316, p = 0.001 in males vs. OR = 1.220, p < 0.001 in females) of MetS compared to those with no exposure. These results showed an association between SHS and a high OR for MetS in both the males and females. Furthermore, sex differences were identified in the associations between SHS and MetS and its components, and SHS was more closely related to MetS, abdominal obesity, and high BP in males than in females.

Effects of Active Chronic Cigarette-Smoke Exposure on Circulating Fibrocytes.

PURPOSE: This study aimed to evaluate the hypothesis that active smoking impacts upon mediators and abundance of circulating fibrocyte cells in smoking-related disease characterised by fibrosis. METHODS: Flow cytometry and enzyme-linked immunosorbent assays were used to investigate blood from five patient groups: healthy never-smokers, healthy current smokers, stable chronic obstructive pulmonary disease (COPD) active smokers, idiopathic pulmonary fibrosis (IPF) never-smokers, and IPF active smokers. RESULTS: A significant inverse dose-response relationship was observed in healthy smokers among cumulative smoking burden (pack-years) and fibrocyte abundance (p = 0.006, r = -0.86). Among serum profibrotic fibrocyte chemokines measured, CCL18 rose significantly alongside fibrocyte numbers in all five subject groups, while having an inverse dose-response relationship with pack-year burden in healthy smokers (p = 0.003, r = -0.89). In IPF, CCL2 rose in direct proportion to fibrocyte abundance irrespective of smoking status but had lower serum levels in those currently smoking (p = < 0.001). For the study population, CXCL12 was decreased in pooled current smokers versus never-smokers (p = 0.03). CONCLUSION: The suppressive effect of current, as distinct from former, chronic smoking on circulating fibrocyte abundance in healthy smokers, and modulation of regulatory chemokine levels by active smoking may have implications for future studies of fibrocytes in smoking-related lung diseases as a potential confounding variable.

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

PURPOSE: 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). EXPERIMENTAL DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.

Impact of Smoking and Chronic Obstructive Pulmonary Disease on All-Cause, Respiratory, and Cardio-Cerebrovascular Mortality.

Introduction: Mortality differences in chronic obstructive pulmonary disease (COPD) between nonsmokers and smokers remain unclear. We compared the risk of death associated with smoking and COPD on mortality. Methods: The study included participants aged ≥40 years who visited pulmonary clinics and were categorised into COPD or non-COPD and smoker or nonsmoker on the basis of spirometry results and cigarette consumption. Mortality rates were compared between groups using statistical analysis for all-cause mortality, respiratory disease-related mortality, and cardiocerebrovascular disease-related mortality. Results: Among 5811 participants, smokers with COPD had a higher risk of all-cause (adjusted hazard ratio (aHR), 1.69; 95% confidence interval (CI), 1.23-2.33) and respiratory disease-related mortality (aHR, 2.14; 95% CI, 1.20-3.79) than nonsmokers with COPD. Non-smokers with and without COPD had comparable risks of all-cause mortality (aHR, 1.39; 95% CI, 0.98-1.97) and respiratory disease-related mortality (aHR, 1.77; 95% CI, 0.85-3.68). However, nonsmokers with COPD had a higher risk of cardiocerebrovascular disease-related mortality than nonsmokers without COPD (aHR, 2.25; 95% CI, 1.15-4.40). Conclusion: The study found that smokers with COPD had higher risks of all-cause mortality and respiratory disease-related mortality compared to nonsmokers with and without COPD. Meanwhile, nonsmokers with COPD showed comparable risks of all-cause and respiratory mortality but had a higher risk of cardiocerebrovascular disease-related mortality compared to nonsmokers without COPD.

A systematic review and meta-analysis of the association between e-cigarette use among non-tobacco users and initiating smoking of combustible cigarettes.

INTRODUCTION: The rapid increase in e-cigarette use over the past decade has triggered an important public health question on the potential association between e-cigarette use and combustible cigarette smoking. Following AMSTAR 2 and PRISMA guidelines, this evidence synthesis sought to identify and characterize any associations between e-cigarette use among individuals not smoking cigarettes and initiation of cigarette smoking. METHODS: The protocol was registered on September 24, 2018 (PROSPERO 2018 CRD42018108540). Three databases were queried from January 01, 2007 to April 26, 2023. Search results were screened using the PICOS review method. RESULTS: Among 55 included studies (40 "good" and 15 "fair"; evidence grade: "high") that adjusted for gender, age, and race/ethnicity between groups, generally, there was a significant association between non-regular e-cigarette use and initiation of cigarette smoking, further supported by the meta-analytic results (AOR 3.71; 95% CI 2.86-4.81). However, smoking initiation was most often measured as ever/current cigarette smoking. Two studies (quality: 2 "good") evaluated progression to regular cigarette smoking among individuals with regular use of e-cigarettes, and generally found no significant associations. One study ("good") evaluated smoking initiation among individuals with regular use of e-cigarettes, finding an increasing probability of ever smoking cigarettes with increased e-cigarette use. Twelve studies (10 "good" and two "fair") examining progression to regular smoking among individuals with non-regular use of e-cigarettes reported inconsistent findings. CONCLUSIONS: Numerous methodological flaws in the body of literature limit the generalizability of these results to all individuals who are not smoking cigarettes with few studies measuring established/regular use/smoking of e-cigarettes and cigarettes. Further, studies did not control adequately for specific confounding variables representing common liabilities between e-cigarette use and cigarette smoking, nor did they account for sufficient follow-up durations. Collectively, these flaws limit the generalizability of findings to the question of an association between e-cigarette use and cigarette smoking initiation.

Prospective comparison of acute severe toxicities between smokers and non-smokers during radiotherapy for head and neck cancers.

BACKGROUND AND PURPOSE: The association between smoking and acute radiation toxicities of head and neck cancer (HNC) is currently unproven. The aim of the study was to compare the occurrence of acute severe toxicity between active and non-active smokers treated for HNC by radiotherapy. MATERIALS AND METHODS: A prospective monocentric cohort study included patients treated by (chemo)radiotherapy for HNC from January 2021 to January 2023. Smoking status was recorded. Patients underwent a medical exam weekly during the radiotherapy to report acute toxicities according to the Common Terminology Criteria for Adverse Effects system version 5.0. Primary endpoint was the occurrence of at least one grade ≥ 3 acute toxicity among mucositis, dysphagia and dermatitis. RESULTS: Among the 102 patients included, 27.4 % were active smokers, 58.8 % were former smokers and 13.7 % had never smoked. Regarding toxicity, 23.5 % (n = 24) patients experienced severe mucositis, 37.2 % (n = 38) severe dysphagia, 13.7 % (n = 14) severe dermatitis and 54.9 % (n = 56) experienced at least one of them. Occurrence of severe acute toxicity was not statistically associated with smoking during radiotherapy (64.3 % among active smokers versus 51.3 % among non-active smokers; p = 0.24). On multivariate analysis, concurrent chemotherapy (87.5 % vs 65.2 %; OR = 5.04 [1.64-15.52]; p = 0.004) and 2.12 Gy versus 2 Gy fractionation schedule (64.3 % vs 41.3 %; OR = 2.53 [1.09-5.90]; p = 0.03) were significantly associated with severe acute toxicity. CONCLUSION: This study did not find an association between smoking during radiotherapy for HNC and occurrence of severe acute toxicities.

Endoscopic reflux esophagitis and decline in pulmonary function in nonsmokers: A retrospective cohort study.

BACKGROUND: The association between reflux esophagitis and pulmonary function remains controversial. Thus, evaluating the relationship between endoscopic reflux esophagitis and changes in pulmonary function over time in a nonsmoking population is an important clinical issue. METHODS: In this single-center retrospective cohort study, a medical examination database at Kameda Medical Center Makuhari was employed to identify nonsmokers who underwent upper gastrointestinal endoscopy and spirometry in 2010 and were followed up in 2015. Gastroenterologists carefully double-checked the diagnosis of reflux esophagitis. Multiple linear regression analyses were performed to compare the decline in the percentage of predicted vital capacity (%VC), forced vital capacity (%FVC), and forced expiratory volume in 1 s (%FEV1) between participants with reflux esophagitis and those without. Furthermore, using multivariable logistic regression analyses, we evaluated the factors associated with rapid decline in %VC, %FVC, and %FEV1, which is defined as a decrease of >10% in each parameter over the 5-year observation period. RESULTS: We identified 3098 eligible subjects, including 72 and 44 participants who had a Los Angeles classification grade A and B-C (severe) reflux esophagitis in 2010, respectively. The decline in %VC was significantly larger in the participants with severe reflux esophagitis than in the control subjects (standardized coefficient, -0.037; 95% confidence interval, -0.071 to -0.004). Moreover, reflux esophagitis was significantly associated with a rapid decline in %VC and %FVC but not in %FEV1 (P for trend: 0.009, 0.009, and 0.276, respectively). CONCLUSIONS: Severe reflux esophagitis among nonsmokers had clinical disadvantages in terms of a decline in %VC.

Bladder Cancer Survivors Who Do Not Smoke Have Better Longitudinal Health-Related Quality of Life Measures: An Assessment of the Comparative Effectiveness and Survivorship Health in Bladder Cancer (CEASE-BC) Study.

PURPOSE: Cigarette smoking is the most common risk factor for the development of bladder cancer (BC), yet there is a paucity of data characterizing the relationship between smoking status and longitudinal health-related quality of life (HRQoL) outcomes in patients with BC. We examined the association between smoking status and HRQoL among patients with BC. MATERIALS AND METHODS: Data were sourced from a prospective, longitudinal study open between 2014 and 2017, which examined HRQoL in patients aged ≥ 18 years old diagnosed with BC across North Carolina. The QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core instrument) was administered at 3, 12, and 24 months after BC diagnosis. Our primary exposure of interest was current smoking status. Linear regression using generalized estimating equations was used to analyze the relationship between smoking status and various domains of the QLQ-C30. RESULTS: A total of 154 patients enrolled in the study. Eighteen percent were classified as smoking at 3 months from diagnosis, and packs per day ranged from < 0.5 to 2. When controlling for time from diagnosis, demographic covariates, cancer stage, and treatment type, mean differences for physical function (7.4), emotional function (5.6), and fatigue measures (-8.2) were significantly better for patients with BC who did not smoke. CONCLUSIONS: Patients with BC who do not smoke have significantly better HRQoL scores in the domains of physical function, emotional function, and fatigue. These results underscore the need to treat smoking as an essential component of BC care.

Evaluation of Oral Mucosal Lesions in Iranian Smokers and Non-smokers.

BACKGROUND: Tobacco smoking statistics are alarming and the oral mucosa is the first human part of the body that is exposed to the toxic substances of smoking. AIMS: Considering the high prevalence rate of tobacco-associated problems in the oral cavity and few studies on the Iranian population regarding the effects of smoking on the oral cavity, this study aimed to evaluate the relationship between smoking and oral lesions in the Iranian population. MATERIALS AND METHODS: Observational study. In this observational study, the oral cavities of 200 participants (smokers = 100 and non-smokers = 100) were examined by a trained dental student under the supervision of an oral and maxillofacial medicine expert, and the presence of coated tongue, leukoedema, leukoplakia, smoker's palate, smoker's melanosis, erythroplakia, frictional hyperkeratosis, acute pseudomembranous candidiasis, and erythematous candidiasis were recorded. Xerostomia was evaluated based on participants' self-reporting through a questionnaire. All data were analyzed using T-test, Chi-square test, odd ratio, 95% confidence interval, Fisher's exact test, and Spearman's rank correlation coefficient. RESULTS: The results of this study showed smoking is significantly associated with an increased risk of coated tongue (OR: 1.80, 95% CI: 1.32-3.54, P = 0.005), smoker's melanosis (OR: 6.176, 95% CI: 3.28-11.62, P = 0.00002), and frictional hyperkeratosis (OR: 1.33, 95% CI: 0.68-2.60, P = 0.005). However, no significant association was observed between smoking and leukoedema (OR: 1, 95% CI: 0.51-1.94, P = 1). None of the participants presented smoker's palate, erythroplakia, and candidiasis. CONCLUSIONS: This study's results showed that smokers exhibited a greater chance of developing oral lesions compared to non-smokers.

A nested case-control study of untargeted plasma metabolomics and lung cancer among never-smoking women within the prospective Shanghai Women's Health Study.

The etiology of lung cancer in never-smokers remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Here, we aimed to enhance our understanding of lung cancer pathogenesis among never-smokers using untargeted metabolomics. This nested case-control study included 395 never-smoking women who developed lung cancer and 395 matched never-smoking cancer-free women from the prospective Shanghai Women's Health Study with 15,353 metabolic features quantified in pre-diagnostic plasma using liquid chromatography high-resolution mass spectrometry. Recognizing that metabolites often correlate and seldom act independently in biological processes, we utilized a weighted correlation network analysis to agnostically construct 28 network modules of correlated metabolites. Using conditional logistic regression models, we assessed the associations for both metabolic network modules and individual metabolic features with lung cancer, accounting for multiple testing using a false discovery rate (FDR) < 0.20. We identified a network module of 121 features inversely associated with all lung cancer (p = .001, FDR = 0.028) and lung adenocarcinoma (p = .002, FDR = 0.056), where lyso-glycerophospholipids played a key role driving these associations. Another module of 440 features was inversely associated with lung adenocarcinoma (p = .014, FDR = 0.196). Individual metabolites within these network modules were enriched in biological pathways linked to oxidative stress, and energy metabolism. These pathways have been implicated in previous metabolomics studies involving populations exposed to known lung cancer risk factors such as traffic-related air pollution and polycyclic aromatic hydrocarbons. Our results suggest that untargeted plasma metabolomics could provide novel insights into the etiology and risk factors of lung cancer among never-smokers.

Comparison of smokers' mortality with non-smokers following out-of-hospital cardiac arrests: a systematic review and meta-analysis.

OBJECTIVE: Although some studies have linked smoking to mortality after out-of-hospital cardiac arrests (OHCAs), data regarding smoking and mortality after OHCAs have not yet been discussed in a meta-analysis. Thus, this study conducted this systematic review to clarify the association. METHODS: The study searched Medline-PubMed, Web of Science, Embase and Cochrane libraries between January 1972 and July 2022 for studies that evaluated the association between smoking and mortality after OHCAs. Studies that reportedly showed relative risk estimates with 95% confidence intervals (CIs) were included. RESULTS: Incorporating a collective of five studies comprising 2477 participants, the analysis revealed a lower mortality risk among smokers in the aftermath of OHCAs compared with non-smokers (odds ratio: 0.77; 95% CI 0.61-0.96; P < 0.05). Egger's test showed no publication bias in the relationship between smoking and mortality after OHCAs. CONCLUSIONS: After experiencing OHCAs, smokers had lower mortality than non-smokers. However, due to the lack of data, this 'smoker's paradox' still needs other covariate effects and further studies to be considered valid.

Proteogenomic Characterization Reveals Estrogen Signaling as a Target for Never-Smoker Lung Adenocarcinoma Patients without EGFR or ALK Alterations.

Never-smoker lung adenocarcinoma (NSLA) is prevalent in Asian populations, particularly in women. EGFR mutations and anaplastic lymphoma kinase (ALK) fusions are major genetic alterations observed in NSLA, and NSLA with these alterations have been well studied and can be treated with targeted therapies. To provide insights into the molecular profile of NSLA without EGFR and ALK alterations (NENA), we selected 141 NSLA tissues and performed proteogenomic characterization, including whole genome sequencing (WGS), transcriptomic, methylation EPIC array, total proteomic, and phosphoproteomic analyses. Forty patients with NSLA harboring EGFR and ALK alterations and seven patients with NENA with microsatellite instability were excluded. Genome analysis revealed that TP53 (25%), KRAS (22%), and SETD2 (11%) mutations and ROS1 fusions (14%) were the most frequent genetic alterations in NENA patients. Proteogenomic impact analysis revealed that STK11 and ERBB2 somatic mutations had broad effects on cancer-associated genes in NENA. DNA copy number alteration analysis identified 22 prognostic proteins that influenced transcriptomic and proteomic changes. Gene set enrichment analysis revealed estrogen signaling as the key pathway activated in NENA. Increased estrogen signaling was associated with proteogenomic alterations, such as copy number deletions in chromosomes 14 and 21, STK11 mutation, and DNA hypomethylation of LLGL2 and ST14. Finally, saracatinib, an Src inhibitor, was identified as a potential drug for targeting activated estrogen signaling in NENA and was experimentally validated in vitro. Collectively, this study enhanced our understanding of NENA NSLA by elucidating the proteogenomic landscape and proposed saracatinib as a potential treatment for this patient population that lacks effective targeted therapies. SIGNIFICANCE: The proteogenomic landscape in never-smoker lung cancer without known driver mutations reveals prognostic proteins and enhanced estrogen signaling that can be targeted as a potential therapeutic strategy to improve patient outcomes.

Psychological predictors of vaping uptake among non-smokers: A longitudinal investigation of New Zealand adults.

INTRODUCTION: Demographic and health factors are known to predict vaping. Less is known about psychological predictors of vaping uptake, particularly among non-smoking adults using longitudinal designs. We aimed to model how psychological factors related to personality and mental health predicted the likelihood of vaping uptake over time in non-smoking adults ages 18+ using longitudinal data. METHODS: Longitudinal regression models utilised data from the 2018-2020 waves of the New Zealand Attitudes and Values Study to assess how the Big Five personality traits, mental distress and self-control predicted who began vaping over time among non-users (non-vapers and non-smokers), controlling for gender, age, ethnicity and economic deprivation. RESULTS: Analyses included 36,309 adults overall (ages 18 to 99; M = 51.0). The number of non-users who transitioned into current vaping was small (transitioned from 2018 to 2019, n = 147; 0.48%; 2019 to 2020, n = 189, 0.63%). Fully adjusted models showed that adults with higher mental distress (adjusted odds ratio [aOR] 1.43; 95% confidence interval [CI] 1.09-1.88), lower self-control (aOR 0.79; 95% CI 0.69-0.89) and higher extraversion (aOR 1.09; 95% CI 1.06-1.13) were more likely to begin vaping at the next time point compared to adults who remained non-users. Higher neuroticism and lower conscientiousness also predicted vaping uptake in initial models, but inclusion of mental distress and self-control superseded these traits. DISCUSSION AND CONCLUSIONS: Psychological factors related to mental distress, impulse control and sociability predicted who was more likely to begin vaping as non-smoking adults. Harm prevention interventions could target these factors to reduce vaping uptake in non-smokers.

The smoker's paradox in transjugular intrahepatic portosystemic shunt procedure: A national inpatient sample analysis from 2015 to 2020.

OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure used to alleviate patients with chronic liver cirrhosis and portal hypertension. Smoking can adversely impact liver function and has been shown to influence liver-related outcomes. This study aimed to examine the impact of smoking on the immediate outcomes of TIPS procedure. MATERIALS AND METHOD: The study compared smokers and non-smokers who underwent TIPS procedures in the National Inpatient Sample (NIS) database from the last quarter of 2015 to 2020. Multivariable analysis was used to compare the in-hospital outcomes post-TIPS. Adjusted pre-procedural variables included sex, age, race, socioeconomic status, indications for TIPS, liver disease etiologies, comorbidities, and hospital characteristics. RESULTS: Compared to non-smokers, smokers had lower risks of in-hospital mortality (7.36% vs 9.88 %, aOR 0.662, p < 0.01), acute kidney injury (25.57% vs 33.66 %, aOR 0.68, p < 0.01), shock (0.45% vs 0.98 %, aOR 0.467, p = 0.02), and transfer out to other hospital facilities (11.35% vs 14.78 %, aOR 0.732, p < 0.01). There was no difference in hepatic encephalopathy or bleeding. Also, smokers had shorter wait from admission to operation (2.76±0.09 vs 3.17±0.09 days, p = 0.01), shorter length of stay (7.50±0.15 vs 9.89±0.21 days, p < 0.01), and lower total hospital cost (148,721± 2,740.7 vs 204,911±4,683.5 US dollars, p < 0.01). Subgroup analyses revealed consistent patterns among both current and past smokers. CONCLUSION: This study compared the immediate outcomes of smokers and non-smokers after undergoing the TIPS procedure. Interestingly, we observed a smokers' paradox, where smoker patients had better outcomes following TIPS. The underlying causes for this smoker's paradox warrant further in-depth exploration.

Tongue cancer in non-smoking and non-alcoholic mother and daughter.

Tongue cancer is more prevalent in male smokers and alcoholics. Although an increased incidence of tongue cancer has been noted in non-smoking and non-alcoholic women, reports of its occurrence in mother and daughter are extremely rare. Here, we report a case of a non-smoking and non-alcoholic mother and her daughter diagnosed and treated surgically for tongue squamous cell carcinoma (SCC). The daughter is still being monitored and the mother died from complications from COVID-19 after 6 years of treatment. This report shows that OSCC should be considered in the differential diagnosis of oral ulcerated lesions in non-smoking and non-alcoholic women, especially if there is a family history of first-degree oral cancer.