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1.
Cancer Res ; 84(9): 1491-1503, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38607364

RESUMO

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.


Assuntos
Adenocarcinoma de Pulmão , Quinase do Linfoma Anaplásico , Receptores ErbB , Estrogênios , Neoplasias Pulmonares , Mutação , Proteogenômica , Transdução de Sinais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Quinase do Linfoma Anaplásico/genética , Quinase do Linfoma Anaplásico/metabolismo , Variações do Número de Cópias de DNA , Receptores ErbB/genética , Receptores ErbB/metabolismo , Estrogênios/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , não Fumantes/estatística & dados numéricos , Prognóstico , Proteogenômica/métodos , Transdução de Sinais/genética
2.
Niger J Clin Pract ; 27(4): 467-474, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38679769

RESUMO

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.


Assuntos
Doenças da Boca , Mucosa Bucal , Fumantes , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Feminino , Mucosa Bucal/patologia , Adulto , Pessoa de Meia-Idade , Doenças da Boca/epidemiologia , Doenças da Boca/etiologia , Fumantes/estatística & dados numéricos , Fumar/epidemiologia , Fumar/efeitos adversos , não Fumantes/estatística & dados numéricos , Prevalência , Adulto Jovem , Xerostomia/epidemiologia , Idoso , Leucoplasia Oral/epidemiologia
3.
J Health Popul Nutr ; 43(1): 57, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671493

RESUMO

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.


Assuntos
não Fumantes , Parada Cardíaca Extra-Hospitalar , Fumantes , Humanos , Parada Cardíaca Extra-Hospitalar/mortalidade , Parada Cardíaca Extra-Hospitalar/terapia , Fumantes/estatística & dados numéricos , não Fumantes/estatística & dados numéricos , Fumar , Feminino , Masculino , Pessoa de Meia-Idade , Idoso
4.
Clin Res Hepatol Gastroenterol ; 48(5): 102323, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38537866

RESUMO

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.


Assuntos
Derivação Portossistêmica Transjugular Intra-Hepática , Fumar , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Fumar/efeitos adversos , Fumar/epidemiologia , Estados Unidos/epidemiologia , Idoso , Mortalidade Hospitalar , Adulto , Fumantes/estatística & dados numéricos , Cirrose Hepática/complicações , Pacientes Internados/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Hipertensão Portal , não Fumantes/estatística & dados numéricos
5.
Oral Oncol ; 152: 106779, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38555750

RESUMO

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.


Assuntos
Neoplasias da Língua , Feminino , Humanos , Pessoa de Meia-Idade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/genética , COVID-19/complicações , Mães , não Fumantes/estatística & dados numéricos , Neoplasias da Língua/patologia , Idoso
6.
J Health Commun ; 27(2): 93-102, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35373715

RESUMO

This study examined the effects of gender-specific pictorial health warning labels contingent on their intended gender and threat levels (for females) in forming anti-smoking intentions. We conducted a within-subject design experiment with smokers and nonsmokers in Singapore (N = 100, 50% men). Each participant viewed 10 warning labels-four female-specific (high and low threat), four gender-neutral (high and low threat), and two male-specific (only low threat)-in a random order, evaluating each label on personal relevance, attention, cognitive elaboration, reactance, and intentions to purchase or avoid smoking. The findings showed that females reported greater relevance, attention, elaboration, and intentions to avoid smoking for low threat female-specific warning labels than male-specific or gender-neutral counterparts. Males reported less attention, elaboration, and relevance for low threat male-specific warning labels than female-specific or gender-neutral counterparts. Under high threat conditions, female-specific and gender-neutral warning labels were equally effective for both genders. No differences were observed by smoking status. Overall, gender-specific warning labels are potentially more effective than gender-neutral ones for deterring smoking in women contingent on low threat levels. By providing a deeper understanding of persuasive mechanisms and boundary conditions for the effects of gender specificity, findings can aid health policymakers in developing better gender-responsive interventions.


Assuntos
Rotulagem de Produtos , Fumar , Produtos do Tabaco , Feminino , Humanos , Intenção , Masculino , não Fumantes/psicologia , não Fumantes/estatística & dados numéricos , Rotulagem de Produtos/métodos , Fatores Sexuais , Singapura , Fumantes/psicologia , Fumantes/estatística & dados numéricos , Fumar/psicologia , Produtos do Tabaco/efeitos adversos
7.
JAMA Netw Open ; 5(2): e2147891, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35142830

RESUMO

Importance: Transitions between e-cigarettes and cigarettes are common among tobacco users, but empirical evidence on the health outcomes of switching tobacco products is scarce. Objectives: To examine changes in urinary biomarkers between baseline and 1-year follow-up among adult tobacco users switching between e-cigarettes and cigarettes. Design, Setting, and Participants: This cohort study used data from wave 1 (baseline, September 2013 to December 2014) and wave 2 (1-year follow-up, October 2014 to October 2015) of the Population Assessment of Tobacco and Health Study. A subset of the probability sample of US adults who voluntarily provided biospecimens at 2 waves was analyzed. Participants were divided into 3 mutually exclusive groups at baseline: exclusive cigarette smokers, exclusive e-cigarette users, and dual users. Data analysis was performed in 2021. Exposures: Harmful and potentially harmful constituents included nicotine metabolites, tobacco-specific nitrosamines (TSNAs; including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL]), metals, polycyclic aromatic hydrocarbons (PAHs), and volatile organic compounds (VOCs). Main Outcomes and Measures: Within-participant changes in 55 urinary biomarkers of exposure (BOEs) to harmful and potentially harmful constituents were examined using multivariable regression models. Results: Among 3211 participants (55.6% women, 68.3% White, 13.2% Black, and 11.8% Hispanic) at baseline, 21.9% of exclusive cigarette users, 42.8% of exclusive e-cigarette users, and 62.1% of dual users changed product use at follow-up (all percentages are weighted). There was a significant reduction in urine concentrations of TSNAs, PAHs, and VOCs when users transitioned from exclusive cigarette to exclusive e-cigarette use, with a 92% decrease in NNAL, from a mean of 168.4 pg/mg creatinine (95% CI, 102.3-277.1 pg/mg creatinine) to 12.9 pg/mg creatinine (95% CI, 6.4-25.7 pg/mg creatinine; P < .001). A similar panel of BOEs decreased when dual users transitioned to exclusive e-cigarette use; NNAL levels decreased by 96%, from a mean of 143.4 pg/mg creatinine (95% CI, 86.7-237.0 pg/mg creatinine) to 6.3 pg/mg creatinine (95% CI, 3.5-11.4 pg/mg creatinine; P < .001). Nicotine metabolites, TSNAs, PAHs, and VOCs significantly increased when baseline exclusive e-cigarette users transitioned to exclusive cigarette use or dual use. Switching from exclusive cigarette use to dual use was not associated with significant decreases in BOEs. Conclusions and Relevance: This national cohort study provides evidence on the potential harm reduction associated with transitioning from exclusive cigarette use or dual use to exclusive e-cigarette use. e-Cigarettes tend to supplement cigarettes through dual use instead of cessation at the population level. Continuous monitoring of BOE at the population level and assessment of BOE change by product transition are warranted, as well as defined adverse health outcomes.


Assuntos
Biomarcadores/urina , Carcinógenos/toxicidade , Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Nicotina/urina , não Fumantes/estatística & dados numéricos , Fumantes/estatística & dados numéricos , Uso de Tabaco/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Exposição por Inalação , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estados Unidos , Adulto Jovem
8.
BMC Pulm Med ; 22(1): 3, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983467

RESUMO

BACKGROUND: Asthma exacerbation threatens patient's life. Several genetic studies have been conducted to determine the risk factors for asthma exacerbation, but this information is still lacking. We aimed to determine whether genetic variants of Oxidative Stress Responsive Kinase 1 (OXSR1), a gene with functions of salt transport, immune response, and oxidative stress, are associated with exacerbation of asthma. METHODS: Clinical data were obtained from 1454 asthmatics and single nucleotide polymorphisms (SNPs) of OXSR1 were genotyped. Genetic associations with annual exacerbation rate were analyzed depending on smoking status. RESULTS: Eleven SNPs were selected using Asian data in the International HapMap database. The common allele of rs1384006 C > T of OXSR1 showed a significantly higher annual exacerbation rate than the rare allele in non-smoking asthmatics (CC vs. CT vs. TT: 0.43 ± 0.04 vs. 0.28 ± 0.03 vs. 0.31 ± 0.09, P = 0.004, Pcorr = 0.039). The frequent exacerbators had a significantly higher frequency of the common allele of rs1384006 C > T than did the infrequent exacerbators (74.4% vs. 55.2%, P = 0.004, Pcorr = 0.038). CONCLUSION: The common allele of rs1384006 C > T of OXSR1 was associated with the asthma exacerbation rate and a higher risk of being a frequent exacerbator, indicating that non-smoking asthmatics who carry common alleles may be vulnerable to asthma exacerbations.


Assuntos
Asma/genética , Proteínas Serina-Treonina Quinases/genética , Adulto , Idoso , Alelos , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , não Fumantes/estatística & dados numéricos , Estresse Oxidativo , Polimorfismo de Nucleotídeo Único , República da Coreia , Fatores de Risco
9.
Psychol Health ; 37(11): 1379-1395, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-34279128

RESUMO

OBJECTIVE: This study aimed to explore E-cigarette (EC) accounts from a small sample of UK adults with varied smoking/EC experiences. This was to contribute to existing knowledge of adult perceptions and understand the factors that encourage or deter use to inform health messaging aimed at professionals, policy makers and the general public. DESIGN: Twelve participants, five men and seven women aged 23-55 years (mean age 32.43) with mixed smoking/EC backgrounds took part in face-to-face interviews, analysed using semantic-level inductive thematic analysis. RESULTS: The analysis identified three key themes. Social influence (1) relates to the understanding of the social representations of ECs. Representation and knowledge (2) captures the impact of varied EC related communication on perception. Aspects of addiction (3) conveys aspects of nicotine addiction and how this influences EC use. CONCLUSION: ECs were generally perceived as more socially acceptable than cigarettes by non-smokers, although there were varying levels of acceptability depending on the type of EC device used. There was also unanimity concerning uncertainty surrounding the devices. Behavioural/sensory elements and personal enjoyment of ECs were consistent elements that encouraged or deterred use. Although non-smokers/vapers did not use the devices, they expressed similar apprehensions to those who did.


Assuntos
não Fumantes , Fumantes , Vaping , Adulto , Feminino , Humanos , Masculino , Sistemas Eletrônicos de Liberação de Nicotina , Fumantes/psicologia , Fumantes/estatística & dados numéricos , Fumar/psicologia , Reino Unido , Adulto Jovem , Pessoa de Meia-Idade , Vaping/prevenção & controle , Vaping/psicologia , Fatores de Risco , não Fumantes/psicologia , não Fumantes/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde
10.
JAMA Cardiol ; 7(2): 195-203, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34878493

RESUMO

Importance: Former heavy smokers (ie, those with ≥20 pack-years of smoking) may have higher atherosclerotic cardiovascular disease (ASCVD) risk than never smokers for up to 16 years after smoking cessation. However, the 2013 pooled cohort equations (PCE) do not account for pack-years of smoking and only consider current vs noncurrent smoking status without distinguishing former smokers from never smokers. Objective: To assess the predictive utility of smoking history when added to the PCE using data from 18 400 person examinations among Framingham offspring participants. Design, Setting, and Participants: This is a retrospective analysis of prospectively collected data from the Framingham Heart Study, a community-based cohort. Framingham Heart Study offspring cohort participants attending their first examination (1971-1975) who were followed-up through December 2016 were included. Exposures: Self-reported current/former/never smoking status, pack-years smoked, and years since quitting. Main Outcomes and Measures: Incident ASCVD (myocardial infarction, fatal/nonfatal ischemic stroke, coronary heart disease death). Results: Of 3908 patients, there were 358 and 197 events among 1895 men and 2013 women, respectively, with a mean (SD) age of 55 (9.5) years. Ever smoking prevalence was high (6474 men [77%] and 7760 women [78%]), as were median pack-years (men: 39; women: 32 overall person examinations). Four sex-specific ASCVD risk prediction models were built using pooled-repeated Cox proportional hazards regression. The PCEs were was fit in this sample with continuous predictors on their natural scale (ie, not logarithmically transformed) as well as polynomials accounting for nonlinearity and then cumulatively adjusted for former smoking, pack-years, and years since quitting. Models were compared via change in C statistic, continuous net reclassification improvement (NRI[>0]), and relative integrated discrimination improvement (rIDI). Including former smoking status, pack-years, and years since quitting had significant but modest NRI(>0) and rIDI values compared with the PCE with continuous variables on their natural scale in both sexes (men: NRI[>0] = 0.23; rIDI = 0.19; women: NRI[>0] = 0.34, rIDI = 0.11; change in C statistic = 0.01 for both). Conclusions and Relevance: Former smoking, pack-years, and years since quitting significantly improved ASCVD risk prediction in this sample. The Framingham Heart Study offspring cohort is largely composed of non-Hispanic White participants of European ancestry. If results are validated in cohorts of race and ethnicity groups other than White, these variables could be considered for inclusion in future ASCVD risk prediction models.


Assuntos
Doenças Cardiovasculares/epidemiologia , Fumar Cigarros/epidemiologia , Ex-Fumantes/estatística & dados numéricos , Fatores de Risco de Doenças Cardíacas , não Fumantes/estatística & dados numéricos , Produtos do Tabaco/estatística & dados numéricos , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Biomed Res Int ; 2021: 5516218, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671675

RESUMO

BACKGROUND: The aim of this study was to identify potential key genes, proteins, and associated interaction networks for the development of lung cancer in nonsmoking women through a bioinformatics approach. METHODS: We used the GSE19804 dataset, which includes 60 lung cancer and corresponding paracancerous tissue samples from nonsmoking women, to perform the work. The GSE19804 microarray was downloaded from the GEO database and differentially expressed genes were identified using the limma package analysis in R software, with the screening criteria of p value < 0.01 and ∣log2 fold change (FC) | >2. RESULTS: A total of 169 DEGs including 130 upregulated genes and 39 downregulated were selected. Gene Ontology and KEGG pathway analysis were performed using the DAVID website, and protein-protein interaction (PPI) networks were constructed and the hub gene module was screened through STING and Cytoscape. CONCLUSIONS: We obtained five key genes such as GREM1, MMP11, SPP1, FOSB, and IL33 which were strongly associated with lung cancer in nonsmoking women, which improved understanding and could serve as new therapeutic targets, but their functionality needs further experimental verification.


Assuntos
Neoplasias Pulmonares/genética , não Fumantes/estatística & dados numéricos , Biomarcadores Tumorais/genética , Biologia Computacional/métodos , Bases de Dados Genéticas , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Mapas de Interação de Proteínas , Taxa de Sobrevida , Transcriptoma
12.
Sci Rep ; 11(1): 20150, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635759

RESUMO

Alcohol consumption and smoking pose a significant risk for esophageal squamous cell neoplasia (ESCN) development in males; however, ESCN is often diagnosed in non-drinking and non-smoking females. The mechanisms underlying these differences remain elusive, and understanding them can potentially identify novel pathways involved in ESCN development. We performed short-read sequencing to identify somatic variants on a cancer panel targeting 409 genes using DNA extracted from the superficial squamous cell carcinoma (ESCC) tissues and adjacent non-neoplastic epithelium (NE), and immunohistochemical staining of the protein encoded by the target gene. All male patients (n = 117) were drinkers or smokers, whereas 45% of the female patients (n = 33) were not. Somatic variants were compared among three age-matched groups: 13 female ESCC patients with smoking and drinking habits (known-risk group, F-KR), 13 female ESCC patients without these habits (unknown-risk group, F-UR), and 27 males with ESCC and smoking and drinking habits (M-KR). In the NE, the frequencies of CDKN2A variants were significantly higher in F-UR than in F-KR and M-KR. In both ESCC and NE, p14ARF was significantly overexpressed in F-UR than in the other groups. In conclusion, CDKN2A might be important in ESCC development, independent of known risk factors.


Assuntos
Consumo de Bebidas Alcoólicas/tendências , Biomarcadores Tumorais/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Esôfago/patologia , não Fumantes/estatística & dados numéricos , Polimorfismo de Nucleotídeo Único , Idoso , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Esôfago/metabolismo , Feminino , Seguimentos , Perfilação da Expressão Gênica , Genômica , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco
13.
Nat Genet ; 53(9): 1348-1359, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34493867

RESUMO

Lung cancer in never smokers (LCINS) is a common cause of cancer mortality but its genomic landscape is poorly characterized. Here high-coverage whole-genome sequencing of 232 LCINS showed 3 subtypes defined by copy number aberrations. The dominant subtype (piano), which is rare in lung cancer in smokers, features somatic UBA1 mutations, germline AR variants and stem cell-like properties, including low mutational burden, high intratumor heterogeneity, long telomeres, frequent KRAS mutations and slow growth, as suggested by the occurrence of cancer drivers' progenitor cells many years before tumor diagnosis. The other subtypes are characterized by specific amplifications and EGFR mutations (mezzo-forte) and whole-genome doubling (forte). No strong tobacco smoking signatures were detected, even in cases with exposure to secondhand tobacco smoke. Genes within the receptor tyrosine kinase-Ras pathway had distinct impacts on survival; five genomic alterations independently doubled mortality. These findings create avenues for personalized treatment in LCINS.


Assuntos
Variações do Número de Cópias de DNA/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , não Fumantes/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Receptores ErbB/genética , Feminino , Genoma/genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Receptores Androgênicos/genética , Fatores de Risco , Fumar/genética , Enzimas Ativadoras de Ubiquitina/genética , Sequenciamento Completo do Genoma , Adulto Jovem
14.
Exp Eye Res ; 212: 108773, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34560088

RESUMO

Tobacco smoking is a risk factor for many ocular diseases. Of the multiple tobacco smoke compounds nicotine and its main metabolite cotinine are likely agents in disease modulation. The interaction of these compounds with exposed tissue is complex and ranges from proinflammatory to potentially neuroprotective properties. We aimed to determine cotinine and cytokines in the vitreous in smokers and non-smokers in this prospective, cross-sectional study at the Department of Ophthalmology, Medical University Graz, Austria. We included 10 smokers and 10 non-smokers. Vitreous and serum samples were analyzed for cotinine and cytokines. The cytokine analysis was performed with multiplex assay and cotinine was quantified with enzyme-linked immunosorbent assay. Cotinine was detectable in smokers only with a mean of 154.0 ng/ml ± 107.3 ng/ml in the vitreous and of 194.1 ng/ml ± 121.3 ng/ml in the serum. The difference between intraocular and systemic levels was statistically significant. There were no statistically significant differences between the cytokine levels of smokers and non-smokers. However, intravitreal VEGF-A was by trend elevated in smokers and correlated positively with intravitreal cotinine (r = 0.59, p = 0.073). In conclusion cotinine is detectable in the vitreous of smokers and is lower than the serum. There is a trend towards elevation of VEGF-A in the vitreous of smokers.


Assuntos
Cotinina/metabolismo , Citocinas/metabolismo , não Fumantes/estatística & dados numéricos , Fumantes/estatística & dados numéricos , Corpo Vítreo/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Estudos Retrospectivos
15.
Int J Cancer ; 149(12): 2010-2019, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34398974

RESUMO

The trends in incidence of lung cancer in never smokers are unclear as well as the significance of risk factors. We studied time trends in the incidence and risk factors of lung cancer in never smokers in Finland in a large, pooled cohort. We pooled data from seven Finnish health cohorts from the period between 1972 and 2015 with 106 193 never smokers. The harmonised risk factors included education, alcohol consumption, physical activity, height and BMI. We retrieved incident lung cancers from the nation-wide Finnish Cancer Registry. We estimated average annual percent change (AAPC) and the effects of risk factors on cause-specific hazard ratios (HRs) of lung cancer using Poisson regression. We detected 47 lung cancers in never smoking men (n = 31 859) and 155 in never smoking women (n = 74 334). The AAPC of lung cancer incidence was -3.30% (95% confidence interval [CI]: -5.68% to -0.88%, P = .009) in never smoking men and 0.00% (95% CI: -1.57% to 1.60%, P = .996) in never smoking women. Of the five studied risk factors only greater height in women had a statistically significant increased risk of lung cancer (multivariate HR = 1.84, 95%CI: 1.08 to 3.12). It is plausible that tobacco control measures focused on working places have reduced passive smoking among men more than among women, which could explain the declining trend in lung cancer incidence in never smoker men but not in never smoker women. As tobacco control measures have not been targeted to domestic environments, it is likely that women's exposure to passive smoking has continued longer.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Neoplasias Pulmonares/epidemiologia , não Fumantes/estatística & dados numéricos , Poluição por Fumaça de Tabaco/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estatura , Índice de Massa Corporal , Estudos de Coortes , Escolaridade , Exercício Físico , Feminino , Finlândia/epidemiologia , Humanos , Incidência , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros/estatística & dados numéricos , Fatores de Risco , Fatores Sexuais , Poluição por Fumaça de Tabaco/prevenção & controle , Adulto Jovem
16.
PLoS One ; 16(7): e0253928, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34242286

RESUMO

PURPOSE: To investigate any associations between cigarette smoking and retinal microvascular changes in diabetic patients without visible retinopathy. DESIGN: Retrospective, cross-sectional study. PARTICIPANTS: 1099 eyes from 1099 diabetic patients with no clinical evidence of diabetic retinopathy (DR) were included in this study. METHODS: Diabetic patients underwent optical coherence tomography angiography (OCTA) scanning at Zuckerberg San Francisco General Hospital and Trauma Center between April 2018 and September 2019. Patient demographic and clinical information was collected. Standard bivariate statistics and multivariate linear regression were performed. MAIN OUTCOME MEASURES: OCTA parameters included metrics related to the foveal avascular zone (FAZ; area, perimeter, circularity), perfusion density (PD; full, center, inner), and vessel length density (VLD; full, center, inner). RESULTS: The study population included 750 non-smokers and 349 smokers. FAZ perimeter was the only OCTA parameter that was significantly different between the two groups on uncontrolled analysis (P = 0.033). Multivariate regression analyses revealed significant associations between lower VLD full (ß = -0.31, P = 0.048), lower VLD inner (ß = -0.35, P = 0.046) and a history of smoking. No significant associations between cigarette smoking and either FAZ or PD were detected. CONCLUSIONS: Our results suggest that smoking is likely associated with deleterious changes in the retinal microvasculature of patients with a history of diabetes and no visible DR. Based on these findings, diabetic patients with a history of smoking may benefit from higher prioritization in terms of ophthalmic screening.


Assuntos
Angiografia/estatística & dados numéricos , Fumar Cigarros/epidemiologia , Retinopatia Diabética/prevenção & controle , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica/estatística & dados numéricos , Idoso , Angiografia/métodos , Fumar Cigarros/efeitos adversos , Estudos Transversais , Retinopatia Diabética/diagnóstico , Ex-Fumantes/estatística & dados numéricos , Feminino , Humanos , Macula Lutea/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , não Fumantes/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Fumantes/estatística & dados numéricos
17.
Asian Pac J Cancer Prev ; 22(7): 1997-2004, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34319019

RESUMO

BACKGROUND: This study investigates the socio-demographic factors associated with smoking status in five Southeast Asian countries: Malaysia, Thailand, Indonesia, Vietnam, and Philippines. METHODS: This cross-sectional study utilizes data of adults ≥15 years who completed the Global Adult Tobacco Surveys. Ordered probit analysis is used to account for the smoking statuses of non-smokers, occasional smokers, and daily smokers. RESULTS: Malaysian and Vietnamese households with more family members face lower smoking likelihoods than otherwise. Urbanites in Philippines and rural residents in Thailand and Indonesia are more likely to smoke on occasional and daily basis than others. Males are consistently more likely to smoke occasionally or daily and less likely to be non-smokers than females across all countries. Younger middle-age (retiree) individuals aged 30-35 (≥60) years in Malaysia and Thailand exhibit higher (lower) likelihoods to smoke occasionally or daily than their younger cohorts aged 15-29 years. Individuals aged 30 years and above in Indonesia, Vietnam, and Philippines display higher daily smoking propensities than others. Higher education levels dampens smoking likelihoods and increases non-smoking propensities in all countries. Non-government or self-employed workers in all countries are more likely to smoke occasionally or daily than unemployed persons. Being married is associated with higher non-smoking likelihoods in Thailand although this association is not evident in Malaysia. CONCLUSION: These findings suggest that a portfolio of targeted interventions is necessary to meet the needs of specific subpopulations within the various countries.
.


Assuntos
Comportamentos Relacionados com a Saúde , não Fumantes/estatística & dados numéricos , Fumantes/estatística & dados numéricos , Fumar/epidemiologia , Produtos do Tabaco/estatística & dados numéricos , Adolescente , Adulto , Idoso , Sudeste Asiático/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
18.
J Reprod Immunol ; 147: 103351, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34293588

RESUMO

INTRODUCTION: Women who smoke during pregnancy have a reduced risk of preeclampsia. The mechanism of this association is poorly understood. Preeclampsia is an anti-angiogenic and inflammatory state. Transforming growth factor beta 1 (TGF-ß1) is a multi-functional anti-inflammatory cytokine that activates membrane bound endoglin on endothelial cells causing a myriad of vascular actions including vasorelaxation. The objective of the study was to determine serum levels of cytokines, angiogenic factors, placental growth factor (PlGF), TGF-ß-1 and anti-angiogenic factors, soluble endoglin (sEng) and soluble vascular endothelial growth factor 1 (sVEGFR1) in smoking and non-smoking pregnant women. METHODS: Using enzyme-linked immunosorbent and multiplex assays we prospectively analyzed serum levels of PIGF, TGF-ß1, sEng, sVEGFR1 and cytokines in normotensive pregnant smokers and non-smokers. Exclusion criteria included maternal hypertension, autoimmune disorders, rupture of membranes, evidence of labor and drug use. RESULTS: There were 59 women in the smoking and 66 in the non-smoking group. Compared to non-smoking mothers. maternal age was lower in smoking mothers with no significant difference in other demographic variables. There was no difference in levels of cytokines, anti-angiogenic factors and PlGF between the two groups. Median TGF-ß1 levels were significantly higher in the smoking group (8120 pg/mL vs 6040 pg/mL, p < 0.001) and remained significant after controlling for confounders. TGF-ß1 levels correlated positively with cotinine levels in the smoking group. CONCLUSIONS: We speculate that higher TGF-ß1 levels may explain the reduced incidence of preeclampsia in mothers who smoke by being available for action on maternal endothelium even after inactivation by circulating maternal sEng.


Assuntos
Pré-Eclâmpsia/epidemiologia , Fumar/imunologia , Fator de Crescimento Transformador beta1/sangue , Adulto , Biomarcadores/sangue , Biomarcadores/metabolismo , Cotinina/sangue , Endoglina/sangue , Endoglina/metabolismo , Feminino , Humanos , Incidência , não Fumantes/estatística & dados numéricos , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/imunologia , Gravidez , Fumantes/estatística & dados numéricos , Fumar/sangue , Fator de Crescimento Transformador beta1/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Adulto Jovem
19.
BMC Cancer ; 21(1): 691, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34112113

RESUMO

BACKGROUND: Patients with Philadelphia-negative Myeloproliferative Neoplasms (MPN) suffer from numerous symptoms and decreased quality of life. Smoking is associated with an increased symptom burden in several malignancies. The aim of this study was to analyze the association between smoking and MPN-related symptom burden and explore MPN patients' opinions on smoking. METHODS: A total of 435 patients with MPN participated in a cross-sectional internet-based survey developed by the Mayo Clinic and the Myeloproliferative Neoplasm Quality of Life Group. Patients reported their demographics, disease characteristics, tobacco use, and opinions on tobacco use. In addition, MPN-related symptoms were reported via the validated 10-item version of the Myeloproliferative Neoplasms Symptom Assessment Form. RESULTS: Current/former smokers reported worse fatigue (mean severity 5.6 vs. 5.0, p = 0.02) and inactivity (mean severity 4.0 vs. 3.4, p = 0.03) than never smokers. Moreover, current/former smokers more frequently experienced early satiety (68.5% vs. 58.3%, p = 0.03), inactivity (79.9% vs. 71.1%, p = 0.04), and concentration difficulties (82.1% vs. 73.1%, p = 0.04). Although not significant, a higher total symptom burden was observed for current/former smokers (mean 30.4 vs. 27.0, p = 0.07). Accordingly, overall quality of life was significantly better among never smokers than current/former smokers (mean 3.5 vs. 3.9, p = 0.03). Only 43.2% of the current/former smokers reported having discussed tobacco use with their physician, and 17.5% did not believe smoking increased the risk of thrombosis. CONCLUSION: The current study suggests that smoking may be associated with increased prevalence and severity of MPN symptoms and underscores the need to enhance patient education and address tobacco use in the care of MPN patients.


Assuntos
Fadiga/diagnóstico , Transtornos Mieloproliferativos/complicações , Qualidade de Vida , Fumar Tabaco/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Ex-Fumantes/estatística & dados numéricos , Fadiga/epidemiologia , Fadiga/etiologia , Feminino , Humanos , Internet/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/psicologia , não Fumantes/estatística & dados numéricos , Prevalência , Índice de Gravidade de Doença , Fumantes/estatística & dados numéricos , Inquéritos e Questionários/estatística & dados numéricos , Fumar Tabaco/efeitos adversos
20.
Medicine (Baltimore) ; 100(23): e26266, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34115020

RESUMO

ABSTRACT: Waon therapy (WT) has been used as a thermal therapy in chronic heart failure patients. However, its effect in patients with hypertension is unclear. This study aimed to reveal the hypotensive effect of WT in patients with hypertension. WT was performed on 31 patients with hypertension (63.9 ±â€Š11.9 years, male: 17) on standard hypertension treatment focusing on lifestyle modification and medication. Systolic and diastolic blood pressures were measured before and after WT using an upper arm automated sphygmomanometer. We investigated the effect of single and repeated (1 time/d, >5 times) WT sessions on blood pressure and further compared its effect between current smoking (n = 11, 55.4 ±â€Š6.4 years, 8.5 ±â€Š2.4 times) and non-smoking (n = 11, 66.9 ±â€Š8.5 years, 12.2 ±â€Š5.9 times) groups. A total of 370 sessions of WT were conducted. Systolic and diastolic blood pressures significantly decreased after a single WT session (systolic blood pressure: 118.5 ±â€Š10.1 to 115.1 ±â€Š9.0 mm Hg, P < .001; diastolic blood pressure: 70.5 ±â€Š6.4 to 65.9 ±â€Š5.3 mm Hg, P < .001). The blood pressure decrease following repeated WT was not significant when all participants were considered (systolic blood pressure: 122.3 ±â€Š15.2 to 116.9 ±â€Š19.6 mm Hg; diastolic blood pressure: 73.8 ±â€Š16.7 to 68.2 ±â€Š13.2 mm Hg); however, it was significant in the non-smoking group (systolic blood pressure: 124.2 ±â€Š11.3 to 108.8 ±â€Š13.4 mm Hg, P < .001; diastolic blood pressure: 73.6 ±â€Š4.9 to 62.1 ±â€Š7.6 mm Hg, P < .001). Repeated WT (at least 5 sessions) decreased blood pressure in patients with hypertension, especially in non-smokers. WT is a simple method to reduce blood pressure in non-smoking patients with hypertension.


Assuntos
Determinação da Pressão Arterial/métodos , Hipertensão , Hipertermia Induzida/métodos , Fumar , Pressão Sanguínea/fisiologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Hipertensão/psicologia , Hipertensão/terapia , Japão , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , não Fumantes/estatística & dados numéricos , Fumar/efeitos adversos , Fumar/fisiopatologia , Resultado do Tratamento
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