Total Pack-years Research Articles

Deployment-related Cigarette Smoking Behaviors and Pulmonary Function Among U.S. Veterans.

The effects of smoking on lung function among post-9/11 Veterans deployed to environments with high levels of ambient particulate matter are incompletely understood. We analyzed interim data (04/2018-03/2020) from the Veterans Affairs (VA) Cooperative Studies Program #595, "Service and Health Among Deployed Veterans". Veterans with ≥1 land-based deployments enrolled at 1 of 6 regional Veterans Affairs sites completed questionnaires and spirometry. Multivariable linear regression models assessed associations between cigarette smoking (cumulative, deployment-related and non-deployment-related) with pulmonary function. Among 1,836 participants (mean age 40.7±9.6, 88.6% male), 44.8% (n = 822) were ever-smokers (mean age 39.5 ± 9.5; 91.2% male). Among ever-smokers, 86% (n = 710) initiated smoking before deployment, while 11% (n = 90) initiated smoking during deployment(s). Smoking intensity was 50% greater during deployment than other periods (0.75 versus 0.50 packs-per-day; P < .05), and those with multiple deployments (40.4%) were more likely to smoke during deployment relative to those with single deployments (82% versus 74%). Total cumulative pack-years (median [IQR] = 3.8 [1, 10]) was inversely associated with post-bronchodilator FEV1%-predicted (-0.82; [95% CI] = [-1.25, -0.50] %-predicted per 4 pack-years) and FEV1/FVC%-predicted (-0.54; [95% CI] = [-0.78, -0.43] %-predicted per 4 pack-years). Deployment-related pack-years demonstrated similar point estimates of associations with FEV1%-predicted (-0.61; [95% CI] = [-2.28, 1.09]) and FEV1/FVC%-predicted (-1.09; [95% CI] = [-2.52, 0.50]) as non-deployment-related pack-years (-0.83; [95% CI] = [-1.26, -0.50] for FEV1%-predicted; -0.52; [95% CI] = [-0.73, -0.36] for FEV1/FVC%-predicted). Although cumulative pack-years smoking was modest in this cohort, an inverse association with pulmonary function was detectable. Deployment-related pack-years had a similar association with pulmonary function compared to non-deployment-related pack-years.

Assessing a Polygenic Risk Score for Lung Cancer Susceptibility in Non-Hispanic White and Black Populations.

Polygenic risk scores (PRS) have become an increasingly popular approach to evaluate cancer susceptibility, but have not adequately represented Black populations in model development. We used a previously published lung cancer PRS on the basis of 80 SNPs associated with lung cancer risk in the OncoArray cohort and validated in UK Biobank. The PRS was evaluated for association with lung cancer risk adjusting for age, sex, total pack-years, family history of lung cancer, history of chronic obstructive pulmonary disease, and the top five principal components for genetic ancestry. Among the 80 PRS SNPs included in the score, 14 were significantly associated with lung cancer risk (P < 0.05) in INHALE White participants, while there were no significant SNPs among INHALE Black participants. After adjusting for covariates, the PRS was significantly associated with risk in Whites (continuous score P = 0.007), but not in Blacks (continuous score P = 0.88). The PRS remained a statistically significant predictor of lung cancer risk in Whites ineligible for lung cancer screening under current U.S. Preventive Services Task Force guidelines (P = 0.02). Using a previously validated PRS, we did find some predictive ability for lung cancer in INHALE White participants beyond traditional risk factors. However, this effect was not observed in Black participants, indicating the need to develop and validate ancestry-specific lung cancer risk models. While a previously published lung cancer PRS was able to stratify White participants into different levels of risk, the model was not predictive in Blacks. Our findings highlight the need to develop and validate ancestry-specific lung cancer risk models.

Polygenic risk scores in assessing lung cancer susceptibility in non-Hispanic White and Black populations.

10548 Background: Polygenic risk scores (PRS) have become an increasingly popular approach to evaluate cancer susceptibility, but have not adequately represented Black patients in model development. We used previously identified single nucleotide polymorphisms (SNPs) and annotated SNPs in associated gene regions to develop PRS in non-Hispanic Whites and Blacks using the INHALE dataset. Methods: Using the Multi-Ethnic Genotype Array, 1,204 SNPs for non-Hispanic Whites and 1,515 SNPs for Blacks were evaluated for their association with lung cancer risk adjusting for age, sex, total pack-years, family history of lung cancer, history of COPD and the top five PCs for genetic ancestry. Gene region-specific significant SNPs (p &lt; 0.05) were used to develop race-specific PRS. Results: The race-specific PRS included different sets of significant SNPs and were highly associated with lung cancer risk in both non-Hispanic Whites (OR = 1.07, 95% CI: 1.05-1.09, p = 3.44x10-9) and Blacks (OR = 1.12, 95% CI: 1.08-1.17, p = 9.14x10-8). These models remained significant for both Whites (OR = 1.05, 95% CI: 1.03-1.09, p = 0.0004) and Blacks (OR = 1.08, 95% CI: 1.01-1.15, p = 0.01) who currently do not meet USPSTF screening guidelines. AUC analysis demonstrated the Black-specific model (AUC = 0.68) outperformed the White-specific model (AUC = 0.57) (p = 0.03) when examined exclusively in the Black cohort. Conclusions: Using previously validated SNPs and gene regions, we developed race-specific PRS in non-Hispanic White and Black INHALE participants. Further validation of PRS could enable the incorporation of genetic risk modeling into lung cancer screening to identify patients who do not have traditional risk factors for lung cancer, as well as stratify patients into different levels of risk based on their genetic profile. Through the development of a reliable genetic risk factor prediction model, clinicians will have another method by which to evaluate lung cancer susceptibility, potentially leading to earlier diagnoses that portend more favorable treatment outcomes.

Chronic Obstructive Pulmonary Disease and Smoking in India: A Meta-Analysis

Introduction: WHO estimates show Chronic obstructive pulmonary disease [COPD] as a growing major global cause of morbidity as well as mortality. An estimated 90% of COPD- related deaths occur in low/middle income countries. India and China together constitutes about one third of the total humanpopulation, accounting for 66% of COPD mortality globally. In the south east Asia region, COPD associated mortality is projected to grow by 160% in the decades ahead. Much of this projection holds pansexual cigarette smoking, improved life expectancy, bulging geriatric population and high levels ofsmall particle pollution, as major causes behind increase in COPD case burden. Methods: The aim of the meta-analysis was to investigate association between COPD and risk factors by pooled and subgroup analysis. We searched for case control studies and studies which are meeting the inclusion criteria. The publications listed in the NCBI PubMed and Cochrane library were searched using the following combination of the key words “COPD”; “smokers”; “health”; “risk” or “factors”;“diagnostic”; “burden”; “exposure”; “disease” or “prevalence” or “morbidity ” or “mortality”; “tobacco”; “smoking”; “smoke”, “India”. Random effects meta-analysis was applied to generate pooled SMD by using CMA software. Results: Data base search identified twenty-nine thousand two hundred twenty-two records and 14 articles made to the cut after implementing the inclusion and exclusion criteria. Main risk factors for COPD were higher age [SMD=0.53, CI= (0.0018-1.05)], total pack years of Smoking [SMD=13.83,CI (10.060-17.616)], FEV1 [SMD=-13.15, CI= (-16.234 to -10.085) and FEV/FVC ratio [SMD=0.915.CI= (0.767-1.063)]. Higher age, smoking, low values of FEV1 and FEV/FVC ratio is directly associated with high risk of COPD. Discussions: The findings of the study shows evidence of smoking history in terms of pack of years as a major risk factor for COPD prevalence. Further research is needed on COPD prevalence andincidence associated with other chemical exposure, to identify how to effectively reduce risks fromexposure to smoking.

Quantitative imaging analysis detects subtle airway abnormalities in symptomatic military deployers

BackgroundExposure to inhalational hazards during post-9/11 deployment to Southwest Asia and Afghanistan puts military personnel at risk for respiratory symptoms and disease. Pulmonary function and qualitative chest high resolution computed tomography (HRCT) are often normal in “deployers” with persistent respiratory symptoms. We explored the utility of quantitative HRCT imaging markers of large and small airways abnormalities, including airway wall thickness, emphysema, and air trapping, in symptomatic deployers with clinically-confirmed lung disease compared to controls.MethodsChest HRCT images from 45 healthy controls and 82 symptomatic deployers with asthma, distal lung disease or both were analyzed using Thirona Lung quantification software to calculate airway wall thickness (by Pi10), emphysema (by percentage of lung volume with attenuation < -950 Hounsfield units [LAA%-950]), and three parameters of air trapping (expiratory/inspiratory total lung volume and mean lung density ratios, and LAA%-856). SAS v.9.4 was used to compare demographic and clinical characteristics between deployers and controls using Chi-Square, Fisher Exact or t-tests. Linear regression was used to assess relationships between pulmonary function and quantitative imaging findings.ResultsGender and smoking status were not statistically significantly different between groups, but deployers were significantly younger than controls (42 vs 58 years, p < 0.0001), had higher body mass index (31 vs 28 kg/m2, p = 0.01), and had fewer total smoking pack-years (8 vs. 26, p = 0.007). Spirometric measures were not statistically significantly different between groups. Pi10 and LAA%-950 were significantly elevated in deployers compared to controls in unadjusted analyses, with the emphysema measure remaining significantly higher in deployers after adjustment for age, sex, smoking, BMI, and expiratory total lung volume. Air trapping parameters were more common in control images, likely due to differences in age and smoking between groups. Among deployers, LAA%-950 and Pi10 were significantly correlated with spirometric markers of obstruction based on ratio of forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) and/or percent predicted FEV1.ConclusionsQuantitative chest HRCT imaging analysis identifies emphysema in deployers with asthma and distal lung disease, and may be useful in detecting and monitoring deployment-related lung disease in a population where spirometry is typically normal.

Tobacco smoking and binge alcohol use are associated with incident venous thromboembolism in an HIV cohort.

People with HIV (PWH) are at increased risk of cardiovascular comorbidities and substance use is a potential predisposing factor. We evaluated associations of tobacco smoking and alcohol use with venous thromboembolism (VTE) in PWH. We assessed incident, centrally adjudicated VTE among 12957 PWH within the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort between January 2009 and December 2018. Using separate Cox proportional hazards models, we evaluated associations of time-updated alcohol and cigarette use with VTE, adjusting for demographic and clinical characteristics. Smoking was evaluated as pack-years and never, former, or current use with current cigarettes per day. Alcohol use was parameterized using categorical and continuous alcohol use score, frequency of use, and binge frequency. During a median of 3.6years of follow-up, 213 PWH developed a VTE. One-third of PWH reported binge drinking and 40% reported currently smoking. In adjusted analyses, risk of VTE was increased among both current (HR: 1.44, 95% CI: 1.02-2.03) and former (HR: 1.44, 95% CI: 0.99-2.07) smokers compared to PWH who never smoked. Additionally, total pack-years among ever-smokers (HR: 1.10 per 5 pack-years; 95% CI: 1.03-1.18) was associated with incident VTE in a dose-dependent manner. Frequency of binge drinking was associated with incident VTE (HR: 1.30 per 7days/month, 95% CI: 1.11-1.52); however, alcohol use frequency was not. Severity of alcohol use was not significantly associated with VTE. Current smoking and pack-year smoking history were dose-dependently associated with incident VTE among PWH in CNICS. Binge drinking was also associated with VTE. Interventions for smoking and binge drinking may decrease VTE risk among PWH.

Vascular remodeling of the small pulmonary arteries and measures of vascular pruning on computed tomography.

Pulmonary hypertension is characterized histologically by intimal and medial thickening in the small pulmonary arteries, eventually resulting in vascular “pruning.” Computed tomography (CT)-based quantification of pruning is associated with clinical measures of pulmonary hypertension, but it is not established whether CT-based pruning correlates with histologic arterial remodeling. Our sample consisted of 138 patients who underwent resection for early-stage lung adenocarcinoma. From histologic sections, we identified small pulmonary arteries and measured the relative area comprising the intima and media (VWA%), with higher VWA% representing greater histologic remodeling. From pre-operative CTs, we used image analysis algorithms to calculate the small vessel volume fraction (BV5/TBV) as a CT-based indicator of pruning (lower BV5/TBV represents greater pruning). We investigated relationships of CT pruning and histologic remodeling using Pearson correlation, simple linear regression, and multivariable regression with adjustment for age, sex, height, weight, smoking status, and total pack-years. We also tested for effect modification by sex and smoking status. In primary models, more severe CT pruning was associated with greater histologic remodeling. The Pearson correlation coefficient between BV5/TBV and VWA% was –0.41, and in linear regression models, VWA% was 3.13% higher (95% CI: 1.95–4.31%, p < 0.0001) per standard deviation lower BV5/TBV. This association persisted after multivariable adjustment. We found no evidence that these relationships differed by sex or smoking status. Among individuals who underwent resection for lung adenocarcinoma, more severe CT-based vascular pruning was associated with greater histologic arterial remodeling. These findings suggest CT imaging may be a non-invasive indicator of pulmonary vascular pathology.

Cell lineage-specific methylome and genome alterations in gout.

In this study, we examined data from 69 gout patients and 1,455 non-gout controls using a MethylationEPIC BeadChip assay and Illumina HiSeq platform to identify lineage-specific epigenetic alterations and associated genetic factors that contributed to gouty inflammation. Cell lineage-specific differentially methylated sites were identified using CellDMC after adjusting for sex, age, alcohol drinking, smoking status, and smoking history (total pack-years). Different cell lineages displayed distinct differential methylation. Ingenuity Pathway Analysis and NetworkAnalyst indicated that many differential methylated sites were associated with interleukin-1β expression in monocytes. On the UCSC Genome Browser and WashU Epigenome Browser, metabolic trait, cis-methylation quantitative trait loci, genetic, and functional annotation analyses identified nine methylation loci located in interleukin-1β-regulating genes (PRKCZ, CIDEC, VDAC1, CPT1A, BIRC2, BRCA1, STK11, and NLRP12) that were associated specifically with gouty inflammation. All nine sites mapped to active regulatory elements in monocytes. MoLoTool and ReMap analyses indicated that the nine methylation loci overlapped with binding sites of several transcription factors that regulated interleukin-1β production and gouty inflammation. Decreases in PRKCZ and STK11 methylation were also associated with higher numbers of first-degree relatives who also had gout. The gouty-inflammation specific methylome and genome alterations could potentially aid in the identification of novel therapeutic targets.

Blood cadmium levels as a marker for early lung cancer detection

BackgroundWe assessed whether blood cadmium levels were associated with incident lung cancer and could be used in the context of a screening program for early-stage lung cancer. Material and methodsWe measured blood cadmium levels among 205 lung cancer patients and 205 matched controls. Cases and controls were matched for sex, age and smoking history (total pack-years, years since cessation for former smokers). ResultsThe odds ratio for those in the highest quartile of cadmium level (versus lowest) was four-fold (OR = 4.41, 95 % CI:2.01–9.67, p < 0.01). The association was present in former smokers (OR = 16.8, 95 % CI:3.96−71.2, p < 0.01), but not in current smokers (OR = 1.23, 95 % CI: 0.34–4.38) or in never smokers (OR not defined). Among former smokers, the association was present in both early- and late-stage lung cancer. ConclusionBlood cadmium levels may be a marker to help with the early detection of lung cancer among former smokers.

Interest in cessation treatment and survival among smokers in a community-based multidisciplinary thoracic oncology program.

2028 Background: Tobacco cessation is essential to high quality oncology care. Many patients smoke when diagnosed and continue to smoke during treatment, which adversely affects treatment response and survival. Although most patients are motivated to quit, few receive effective cessation therapy. The multidisciplinary clinic (MDC), where patients, their caregivers, and key specialists coordinate care, is an ideal setting to integrate a cessation program. To assess the need for cessation services within a MDC setting, we surveyed incoming patients about their smoking status, interest in quitting, and willingness to participate in a clinic-based cessation program. Methods: The study was conducted in the Multidisciplinary Thoracic Oncology Program at Baptist Cancer Center, Memphis TN. We evaluated sociodemographic/clinical characteristics, smoking status, and tobacco dependence of consecutive new patients diagnosed with lung cancer from 2014-2019, who completed a social history questionnaire. Current smokers reported their interest in quitting and their willingness to participate in a cessation program. Chi square tests and logistic regression models were used to compare characteristics of those who would participate vs. those who would not/were unsure. Kaplan-Meier curves and multivariable Cox regression were used to evaluate the association between willingness to participate in a cessation program and overall survival, adjusted for age, sex, race, and total pack-years of smoking. Results: Of 641 patients, the average age was 69 years (range: 32-95), 47% were men, 64% white/34% black, and 17% college graduates; 90% had ever smoked, 34% currently smoked, and 24% quit smoking within the past year. Among current smokers, 60% were very interested in quitting and 37% would participate in a clinic-based cessation program. Willingness to participate was associated with greater interest in quitting (p = 0.0010) and greater overall survival (log rank p = 0.01;HR: 0.48, 95% CI: 0.24-0.95) but was not associated with any sociodemographic, clinical, or smoking-related characteristics. Conclusions: Over half (58%) of patients in a community-based MDC program were current smokers/recent quitters. Willingness to participate in a cessation program was associated with improved survival, suggesting patients with favorable prognoses are especially interested in receiving cessation support. There is considerable need for cessation services and relapse-prevention support within a coordinated, MDC lung cancer care setting.

Lung Cancer Screening: Characteristics of Nonparticipants and Potential Screening Barriers

BackgroundPatients eligible and referred for lung cancer screening (LCS) may not complete the visit. We aimed to identify differences in demographic, clinical, and socioeconomic characteristics between LCS participants and LCS-eligible nonparticipants and determine potential reasons for nonparticipation. Materials and MethodsLCS-eligible patients referred between April 2015 and August 2016 were divided into participants and nonparticipants. Retrospective data were collected. A telephone survey was conducted in a subset of nonparticipants to identify reasons for not participating and assess their understanding of the benefits and harms of LCS. ResultsWe identified 542 participants and 276 LCS-eligible nonparticipants. Female sex, lower pack-years, active smoking, the absence of a history of chronic obstructive pulmonary disease, coronary artery disease, or liver disease, and chronic kidney disease or a history of malignancy were associated with not participating. One hundred nonparticipants completed the telephone survey—29% were unaware of the appointment; 19% had concerns about the distance from the screening site and 14% with insurance coverage; 10% had fear of the imaging result; and 10% felt the computed tomography scan was unnecessary. Eighteen percent knew the benefit of LCS, and 69% were not aware of any screening harms. ConclusionsLCS-eligible nonparticipants are more likely to be female, active smokers, have fewer total pack-years of smoking, chronic kidney disease, a history of prior malignancy, and not have chronic obstructive pulmonary disease, coronary artery disease, or liver disease. Targeted education about the benefits and harms of LCS, verification of insurance coverage, and providing convenient screening locations may improve participation.

P6136Intense daily cigarette smoking accelerates vascular damage of smokers with a moderate cumulative tobacco smoke exposure

Abstract Purpose Coronary artery disease death has been associated with increased cigarette smoking intensity. Aim of the study is to investigate the impact of cigarette smoking intensity on vascular function and structure changes among male smokers with similar age at starting smoking and moderate cumulative tobacco smoke exposure. Methods Indices of vascular function and structure including carotid-femoral pulse wave velocity (PWV), brachial flow-mediated dilation (bFMD), carotid intima media thickness (cIMT) and microvascular damage (penile vasculature) were measured in 118 smokers consuming up to 1 pack (20 cigarettes)/day and 58 patients smoking &gt;1 pack (20 cigarettes)/day. The two groups had a similar mean cigarette smoking exposure (32 pack/years). Microvascular damage was examined by measuring penile peak systolic velocity (PSV) with a dynamic penile color Doppler ultrasonography after intracavernous injection of prostanglandin E1. Lower PSV values indicate severe penile vascular disease. Results The individuals smoking more than 1 pack/day were 10 years younger than smokers consuming up to 1 pack/day, however systolic, diastolic blood pressure, body-mass index, fasting blood glucose levels, lipid profile, C-reactive protein and total testosterone concentration were similar between the two groups. Figure shows mean bFMD, penile PSV, PWV and cIMT of the two groups. Interestingly, despite the similar cumulative smoking exposure between the two groups, the younger in age individuals with the intense cigarette smoking history had significantly lower mean bFMD and penile PSV (all P&lt;0.05) and similar PWV and cIMT compared to the mean values of older subjects smoking up to 1 pack/day. Smoking intensity and vascular changes Conclusions Intense daily smoking accelerates damage of large arteries and significantly impairs microvascular and systemic endothelial function. Considering the predictive value of vascular biomarkers, the findings of this study imply the possibility that baseline daily smoking intensity could be a better summary measure of smoking-related cardiovascular risk among young heavy smokers, relative to total pack-years of smoking.

Clonal Hematopoiesis in Older Women with Extremely Skewed, Non-Random X-Inactivation Is Associated with Previous Cardiovascular and Cerebrovascular Events

Clonal Hematopoiesis in Older Women with Extremely Skewed, Non-Random X-Inactivation Is Associated with Previous Cardiovascular and Cerebrovascular Events

Active and passive smoking impacts on asthma with quantitative and temporal relations: A Korean Community Health Survey

This study aimed to evaluate the relations of smoking with asthma and asthma-related symptoms, considering quantitative and temporal influences. The 820,710 Korean adults in the Korean Community Health Survey in 2009, 2010, 2011, and 2013 were included and classified as non-smoker, past smoker or current smoker. Total smoking years, total pack-years, and age at smoking onset were assessed. Information on wheezing, exercise wheezing, and aggravation of asthma in the past 12 months and asthma diagnosis history and current treatment was collected. Multiple logistic regression analysis with complex sampling was used. Current and former smokers showed significant positive relations with wheezing, exercise wheezing, asthma ever, current asthma, and asthma aggravation. Current smokers demonstrated higher adjusted odd ratios (AORs) for wheezing, exercise wheezing, and asthma aggravation than former smokers. Former smokers showed higher AORs than current smokers for current asthma treatment. Longer passive smoking was related to wheezing and exercise wheezing. Greater age at smoking onset and duration since cessation were negatively related to wheezing, exercise wheezing, and current asthma; total pack-years demonstrated proportional associations with these symptoms. Former, current, and passive smoking was positively correlated with wheezing and exercise wheezing. Total pack-years and early initiation were increasingly related to asthma.

MP06-02 THE IMPACT OF SMOKING ON GENOMIC ALTERATIONS IN MUSCLE-INVASIVE BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Epidemiology & Evaluation I1 Apr 2018MP06-02 THE IMPACT OF SMOKING ON GENOMIC ALTERATIONS IN MUSCLE-INVASIVE BLADDER CANCER Roland Seiler, Rink Michael, Atiqullah Aziz, Kees Hendricksen, Alex Wyatt, Peter C. Black, Friedrich-Carl von Rundstedt, Ewan A. Gibb, Shahrokh F. Shariat, Cedric Poyet, Florian Roghmann, and Xylinas Evanguelos Roland SeilerRoland Seiler More articles by this author , Rink MichaelRink Michael More articles by this author , Atiqullah AzizAtiqullah Aziz More articles by this author , Kees HendricksenKees Hendricksen More articles by this author , Alex WyattAlex Wyatt More articles by this author , Peter C. BlackPeter C. Black More articles by this author , Friedrich-Carl von RundstedtFriedrich-Carl von Rundstedt More articles by this author , Ewan A. GibbEwan A. Gibb More articles by this author , Shahrokh F. ShariatShahrokh F. Shariat More articles by this author , Cedric PoyetCedric Poyet More articles by this author , Florian RoghmannFlorian Roghmann More articles by this author , and Xylinas EvanguelosXylinas Evanguelos More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.194AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Smoking is the most important risk factor for developing muscle-invasive bladder cancer (MIBC). The incidence of MIBC, as with lung cancer, correlates directly to both the duration (years) of smoking and the number of cigarettes smoked per day. Carcinogenic toxins similar to cigarette smoke are administered to rodents to model the effects of smoking on the development of MIBC. Here we aimed to investigate the correlation between genomic alterations present in MIBC and the patient smoking status. Furthermore, we compared these findings with genomic alterations present in lung adenocarcinoma (LAC) and with the biological characteristics of chemically induced MIBC in rodents. METHODS Clinical and genomic data from MIBC and LAC were downloaded from the TCGA and MSK-IMPACT (cbioportal.org). The TCGA dataset contained genomic DNA sequencing, mutation count in Signature 5*, total mutational burden, RNA sequencing, follow-up, pack years and smoking history (current/former/never). By using the gene expression data, molecular subtype calls were generated by our recently published genomic subtyping classifier. From the MSK-IMPACT dataset, mutational burden and smoking history were used. The effects of smoking exposure on patient outcome, mutational burden, Signature 5* and molecular subtypes was analyzed in these datasets. RESULTS In the bladder TCGA, smoking history, as well as pack years, were not related to disease-free (p=0.4) or to overall survival (p=0.2). There was no association of smoking history (p=0.8) or pack years (p=0.9) to mutational burden in either the bladder TCGA or the MSK-IMPACT datasets. Mutation count in Signature 5* was higher in former or current smokers, but this did not reach significance (p=0.051). This was in contrast to findings in LAC. Mutational burden was higher in cases with more pack years (p=.005). Moreover, current and former smokers had a higher mutational burden when compared to never smokers. Although others have reported that carcinogen-induced MIBC in rodents has almost exclusively a basal-like phenotype (Kim PloS one 2011; Bivalacqua J Urol 2017), a similar association between smoking history and molecular subtypes of MIBC in TCGA patients was not apparent. We generated subtype calls using other published methods for molecular subtyping (Sjödahl Clin Cancer Res 2012, Choi Cancer Cell 2014, TCGA Nature 2014) but found here also no enrichment of one molecular subtype in current and/or former smokers. CONCLUSIONS Although smoking is recognized as a major risk factor for developing MIBC, its impact on genomic alterations in MIBC is not obvious. This is in contrast to LAC in which smokers have a higher mutational burden and enrichment of mutations in known oncogenes (e.g. TP53). Cigarette smoke contains over 4000 compounds, which may prevent a direct comparison to the rodent model that is induced by a single toxin. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e52 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Roland Seiler More articles by this author Rink Michael More articles by this author Atiqullah Aziz More articles by this author Kees Hendricksen More articles by this author Alex Wyatt More articles by this author Peter C. Black More articles by this author Friedrich-Carl von Rundstedt More articles by this author Ewan A. Gibb More articles by this author Shahrokh F. Shariat More articles by this author Cedric Poyet More articles by this author Florian Roghmann More articles by this author Xylinas Evanguelos More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The association between smoking and cancer incidence in BRCA1 and BRCA2 mutation carriers.

Tobacco smoke is an established carcinogen, but the association between tobacco smoking and cancer risk in BRCA mutation carriers is not clear. The aim of this study was to evaluate prospectively the association between tobacco smoking and cancer incidence in a cohort of BRCA1 and BRCA2 mutation carriers. The study population consisted of unaffected BRCA mutation carriers. Information on lifestyle including smoking histories, reproductive factors, and past medical histories was obtained through questionnaires. Incident cancers were updated biennially via follow-up questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using time-dependent Cox regression models. There were 700 incident cancers diagnosed over 26,711 person-years of follow-up. The most frequent cancers seen in BRCA mutation carriers were breast (n = 428; 61%) and ovarian (n = 109; 15%) cancer. Compared to nonsmokers, (ever) smoking was associated with a modest increased risk of all cancers combined (HR = 1.17; 95%CI 1.01-1.37). Women in the highest group of total pack-years (4.3-9.8) had an increased risk of developing any cancer (HR = 1.27; 95%CI 1.04-1.56), breast cancer (HR = 1.33, 95%CI 1.02-1.75), and ovarian cancer (HR = 1.68; 95%CI 1.06-2.67) compared to never smokers. The associations between tobacco smoking and cancer did not differ by BRCA mutation type or by age at diagnosis. This prospective study suggests that tobacco smoking is associated with a modest increase in the risks of breast and ovarian cancer among women with BRCA1 or BRCA2 mutation.

Chronic Smoking is Not Associated with Increased Postoperative Opioid Use in Patients with Lung Cancer or Esophageal Cancer

Chronic smokers show differences in pain sensitivity compared to healthy non-smokers. Yet, no study to date has examined whether smoker status has an effect on postoperative pain. We aim to examine a possible correlation between preoperative smoking and postoperative opioid dose based on the hypothesis that smokers would use higher doses of opioids to manage increased postoperative pain. A retrospective observational cohort study. The National Cancer Center in Korea. We examined medical record data for patients who had undergone curative resection for either lung or esophageal cancer (lobectomy or bilobectomy for lung cancer or an Ivor Lewis operation for esophageal cancer) between January 1, 2006 and December 31, 2010. We examined the correlation between the total preoperative average number of packs per day multiplied by years of cigarette smoking (pack-years) and morphine equivalent daily doses administered to patients after surgery, considering each type of cancer both individually and together. Partial correlation and regression analyses were performed to determine the causality of a possible relationship between pack-years of cigarette smoking and postoperative opioid dose. A total of 1,129 patients (871 patients with lung cancer and 258 patients with esophageal cancer) were included in the final analysis. There was no significant correlation between total pack-years of cigarette smoking and postoperative opioid dose for lung cancer, esophageal cancer, or both cancer types combined (r = 0.042, -0.012, and 0.037, respectively). In the analysis of both cancer types combined, video-assisted thoracic surgery (VATS) was associated with an 11.1% decrease in opioid dose (β = -0.111, P = 0.003) and epidural analgesia was associated with a 7.2% increase in opioid dose (β = 0.072, P = 0.042). The retrospective design of this study is a limitation. Our study did not observe a correlation between preoperative smoking and postoperative opioid dose in patients with lung or esophageal cancer. Smoking, postoperative pain, opioid, lung cancer, esophageal cancer, analgesia.

Cigarette smoking and the association with serous ovarian cancer in African American women: African American Cancer Epidemiology Study (AACES)

Smoking is a risk factor for mucinous ovarian cancer (OvCa) in Caucasians. Whether a similar association exists in African Americans (AA) is unknown. We conducted a population-based case-control study of incident OvCa in AA women across 11 geographic locations in the US. A structured telephone interview asked about smoking, demographic, health, and lifestyle factors. Odds ratios and 95% confidence intervals (OR, 95% CI) were estimated from 613 cases and 752 controls using unconditional logistic regression in multivariable adjusted models. Associations were greater in magnitude for serous OvCa than for all OvCa combined. Compared to never smokers, increased risk for serous OvCa was observed for lifetime ever smokers (1.46, 1.11-1.92), former smokers who quit within 0-2years of diagnosis (5.48, 3.04-9.86), and for total pack-years smoked among lifetime ever smokers (0-5 pack-years: 1.79, 1.23-2.59; >5-20 pack-years: 1.52, 1.05-2.18; >20 pack-years: 0.98, 0.61-1.56); however, we observed no dose-response relationship with increasing duration or consumption and no significant associations among current smokers. Smoking was not significantly associated with mucinous OvCa. Associations for all OvCa combined were consistently elevated among former smokers. The proportion of ever smokers who quit within 0-2years was greater among cases (23%) than controls (7%). Cigarette smoking may be associated with serous OvCa among AA, which differs from associations reported among Caucasians. Exposure misclassification or reverse causality may partially explain the absence of increased risk among current smokers and lack of dose-response associations. Better characterization of smoking patterns is needed in this understudied population.

HIV Infection Is Associated with Shortened Telomere Length in Ugandans with Suspected Tuberculosis.

IntroductionHIV infection is a risk factor for opportunistic pneumonias such as tuberculosis (TB) and for age-associated health complications. Short telomeres, markers of biological aging, are also associated with an increased risk of age-associated diseases and mortality. Our goals were to use a single cohort of HIV-infected and HIV-uninfected individuals hospitalized with pneumonia to assess whether shortened telomere length was associated with HIV infection, TB diagnosis, and 2-month mortality.MethodsThis was a sub-study of the IHOP Study, a prospective observational study. Participants consisted of 184 adults admitted to Mulago Hospital in Kampala, Uganda who underwent evaluation for suspected TB and were followed for 2 months. Standardized questionnaires were administered to collect demographic and clinical data. PBMCs were isolated and analyzed using quantitative PCR to determine telomere length. The association between HIV infection, demographic and clinical characteristics, and telomere length was assessed, as were the associations between telomere length, TB diagnosis and 2-month mortality. Variables with a P≤0.2 in bivariate analysis were included in multivariate models.ResultsNo significant demographic or clinical differences were observed between the HIV-infected and HIV-uninfected subjects. Older age (P<0.0001), male gender (P = 0.04), total pack-years smoked (P<0.001), alcohol consumption in the past year (P = 0.12), and asthma (P = 0.08) were all associated (P≤0.2) with shorter telomere length in bivariate analysis. In multivariate analysis adjusting for these five variables, HIV-positive participants had significantly shorter telomeres than HIV-negative participants (β = -0.0621, 95% CI -0.113 to -0.011, P = 0.02). Shortened telomeres were not associated with TB or short-term mortality.ConclusionsThe association between HIV infection and shorter telomeres suggests that HIV may play a role in cellular senescence and biological aging and that shorter telomeres may be involved in age-associated health complications seen in this population. The findings indicate a need to further research the impact of HIV on aging.

Influence of cigarette smoking on cardiac biomarkers: the Atherosclerosis Risk in Communities (ARIC) Study.

Cigarette smoking has been associated with incident heart failure independent of coronary artery disease (CAD), but the mechanisms linking smoking to cardiac damage are not well understood. This study sought to evaluate the relationship between smoking and N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity Troponin T (hs-TnT), which are, respectively, biomarkers of myocardial wall stress and injury, in a large community-based cohort. We examined the association between smoking history and NT-proBNP and hs-TnT in 9649 participants free of overt CAD or heart failure from the Atherosclerosis Risk in Communities (ARIC) Study who attended Visit 4 (1996-1998), as well as the association with change in these biomarkers from Visit 4 to Visit 5 (2011-2013) in 3151 participants. At Visit 4, higher cumulative cigarette exposure, assessed by total pack-years, was associated with elevated levels of NT-proBNP (P < 0.001) and hs-TnT (P = 0.01) among ever smokers in multivariable analyses adjusted for potential confounders. After 15 years of follow-up, participants who were active smokers at Visit 4 had greater incidence of elevated NT-proBNP {adjusted proportion = 48% [95% confidence interval (CI) 41, 54] vs. 35 (95% CI 32, 39); P = 0.006} and hs-TnT [adjusted proportion = 32% (95% CI 26, 38) vs. 23 (95% CI 20, 26); P = 0.021] compared with never smokers, adjusting for baseline and follow-up covariates. In a large community-based cohort free of overt CAD and heart failure, cigarette smoking was associated with biomarkers of myocardial wall stress and injury at baseline as well as with a continued measurable increase in these biomarkers after 15 years of follow-up.