scholarly journals Smoking-dependent expression alterations in nasal epithelium reveal immune impairment linked to germline variation and lung cancer risk

2021 ◽  
Author(s):  
Maria Stella de Biase ◽  
Florian Massip ◽  
Tzu-Ting Wei ◽  
Federico Manuel Giorgi ◽  
Rory Stark ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Lung Cancer Risk ◽  
Lung Cancer Mortality ◽  
Lung Cancers ◽  
Transcriptomic Data ◽  
Incidence And Mortality ◽  
Immune Alterations ◽  
Former Smokers ◽  
Lifestyle Risk

Lung cancer is the leading cause of cancer-related death in the world. In contrast to many other cancers, a direct connection to lifestyle risk in the form of cigarette smoke has long been established. More than 50% of all smoking-related lung cancers occur in former smokers, often many years after smoking cessation. Despite extensive research, the molecular processes for persistent lung cancer risk are unclear. CT screening of current and former smokers has been shown to reduce lung cancer mortality by up to 26%. To examine whether clinical risk stratification can be improved upon by the addition of genetic data, and to explore the mechanisms of the persisting risk in former smokers, we have analyzed transcriptomic data from accessible airway tissues of 487 subjects. We developed a model to assess smoking associated gene expression changes and their reversibility after smoking is stopped, in both healthy subjects and clinic patients. We find persistent smoking-associated immune alterations to be a hallmark of the clinic patients. Integrating previous GWAS data using a transcriptional network approach, we demonstrate that the same immune and interferon related pathways are strongly enriched for genes linked to known genetic risk factors, demonstrating a causal relationship between immune alteration and lung cancer risk. Finally, we used accessible airway transcriptomic data to derive a non-invasive lung cancer risk classifier. Our results provide initial evidence for germline-mediated personalised smoke injury response and risk in the general population, with potential implications for managing long-term lung cancer incidence and mortality.

Assessment of feasibility and willingness of former heavy smokers to participate in chemoprevention trials to prevent lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21155-e21155
Author(s):  
Nagi B. Kumar ◽  
Gwendolyn P. Quinn ◽  
Theresa Crocker ◽  
Mark Alexandrow ◽  
Jhanelle Elaine Gray ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Lung Cancer Risk ◽  
Smoking History ◽  
Cancer Center ◽  
X Rays ◽  
Lung Cancers ◽  
Multiple Blood ◽  
Former Smokers ◽  
Heavy Smokers

e21155 Background: Over 50% of new lung cancers occur in former smokers, who often are seeking strategies to reduce their lung cancer risk. However, recruitment and retention of participants in chemoprevention trials continues to be costly and presents unique challenges. Evaluation of feasibility and knowledge of challenges are critical to inform design and ensure accrual in chemoprevention trials.The study assessed interest and willingness of former heavy smokers to participate in a chemoprevention clinical trial using a botanical agent to prevent lung cancer. Methods: An introductory letter and survey instrument that included the goal of the survey, epidemiological and smoking history, acceptability of trial procedures, perception of lung cancer risk and interest in participating in this trial were mailed to 500 consecutive, former heavy smokers with no cancer from a database of 826 subjects at the Moffitt Cancer Center. Results: 202 (40.4%) men and women returned completed surveys. 98% of respondents were over age 60 and 56% had an undergraduate education or higher. The average years smoked was 40.7 (SD 11.9) pack years. 76% believed there was a 50% chance or greater of developing lung cancer. In response to interest and motivation to participate, 92-96% reported interest in receiving free lung exams, health status monitoring and knowing their lung cancer risk. 88% were interested in being a part of a trial to evaluate a botanical agent for lung cancer prevention. Over 92% of subjects reported a willingness to comply with study requirements, multiple blood draws and trips to the Center, spiral CTs and chest x-rays. Subjects were relatively less enthusiastic (73-79%) about undergoing bronchoscopy, taking multiple study agents and possible assignment to a placebo arm. Conclusions: Our study strongly suggests feasibility, highlights potential challenges and the significant interest and willingness of former smokers to participate in chemoprevention trials.

scholarly journals Utilizing Lung Cancer Risk Prediction Models to Promote Smoking Cessation: Two Randomized Controlled Trials

2016 ◽  
Vol 32 (5) ◽  
pp. 1196-1205 ◽  
Author(s):  
Frances C. Sherratt ◽  
Michael W. Marcus ◽  
Jude Robinson ◽  
John K. Field
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Randomized Controlled Trials ◽  
Risk Model ◽  
Lung Cancer Risk ◽  
Smoking Status ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Former Smokers

Purpose: The current project sought to examine whether delivery of lung cancer risk projections (calculated using the Liverpool Lung Project [LLP] risk model) predicted follow-up smoking status. Design: Two single-blinded randomized controlled trials. Setting: Stop Smoking Services in Liverpool (United Kingdom). Participants: Baseline current smokers (N = 297) and baseline recent former smokers (N = 216) were recruited. Intervention: Participants allocated to intervention groups were provided with personalized lung cancer risk projections, calculated using the LLP risk model. Measures: Baseline and follow-up questionnaires explored sociodemographics, smoking behavior, and lung cancer risk perceptions. Analysis: Bivariate analyses identified significant differences between randomization groups, and logistic regression models were developed to investigate the intervention effect on the outcome variables. Results: Lung cancer risk projections were not found to predict follow-up smoking status in the trial of baseline current smokers; however, they did predict follow-up smoking status in the trial of baseline recent former smokers (odds ratio: 1.91; 95% confidence interval: 1.03-3.55). Conclusion: The current study suggests that lung cancer risk projections may help maintain abstinence among individuals who have quit smoking, but the results did not provide evidence to suggest that lung cancer risk projections motivate current smokers to quit.

scholarly journals White Blood Cell Count and Risk of Incident Lung Cancer in the UK Biobank

2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Jason Y Y Wong ◽  
Bryan A Bassig ◽  
Erikka Loftfield ◽  
Wei Hu ◽  
Neal D Freedman ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Blood Cell ◽  
White Blood Cell ◽  
Lung Cancer Risk ◽  
Uk Biobank ◽  
Former Smokers ◽  
Never Smokers ◽  
The Uk ◽  
Incident Cases

Abstract Background The contribution of measurable immunological and inflammatory parameters to lung cancer development remains unclear, particularly among never smokers. We investigated the relationship between total and differential white blood cell (WBC) counts and incident lung cancer risk overall and among subgroups defined by smoking status and sex in the United Kingdom (UK). Methods We evaluated 424 407 adults aged 37–73 years from the UK Biobank. Questionnaires, physical measurements, and blood were administered and collected at baseline in 2006–2010. Complete blood cell counts were measured using standard methods. Lung cancer diagnoses and histological classifications were obtained from cancer registries. Multivariable Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence intervals of incident lung cancer in relation to quartiles (Q) of total WBC and subtype-specific counts, with Q1 as the reference. Results There were 1493 incident cases diagnosed over an average 7-year follow-up. Overall, the highest quartile of total WBC count was statistically significantly associated with elevated lung cancer risk (HRQ4 = 1.67, 95% CI = 1.41 to 1.98). Among women, increased risks were found in current smokers (ncases / n = 244 / 19 464, HRQ4 = 2.15, 95% CI = 1.46 to 3.16), former smokers (ncases / n = 280 / 69 198, HRQ4 = 1.75, 95% CI = 1.24 to 2.47), and never smokers without environmental tobacco smoke exposure (ncases / n = 108 / 111 294, HRQ4 = 1.93, 95% CI = 1.11 to 3.35). Among men, stronger associations were identified in current smokers (ncase s / n = 329 / 22 934, HRQ4 = 2.95, 95% CI = 2.04 to 4.26) and former smokers (ncases / n = 358/71 616, HRQ4 = 2.38, 95% CI = 1.74 to 3.27) but not in never smokers. Findings were similar for lung adenocarcinoma and squamous cell carcinoma and were driven primarily by elevated neutrophil fractions. Conclusions Elevated WBCs could potentially be one of many important markers for increased lung cancer risk, especially among never-smoking women and ever-smoking men.

scholarly journals C-Reactive Protein and Risk of Lung Cancer

2010 ◽  
Vol 28 (16) ◽  
pp. 2719-2726 ◽  
Author(s):  
Anil K. Chaturvedi ◽  
Neil E. Caporaso ◽  
Hormuzd A. Katki ◽  
Hui-Lee Wong ◽  
Nilanjan Chatterjee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Lung Cancer Risk ◽  
Smoking Status ◽  
Lung Carcinogenesis ◽  
C Reactive Protein ◽  
Baseline Serum ◽  
Reactive Protein ◽  
Former Smokers

Purpose Chronic inflammation could play a role in lung carcinogenesis, underscoring the potential for lung cancer prevention and screening. We investigated the association of circulating high-sensitivity C-reactive protein (CRP, an inflammation biomarker) and CRP single nucleotide polymorphisms (SNPs) with prospective lung cancer risk. Patients and Methods We conducted a nested case-control study of 592 lung cancer patients and 670 controls with available prediagnostic serum and 378 patients and 447 controls with DNA within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N = 77,464). Controls were matched to patients on age, sex, entry year, follow-up time, and smoking. We measured CRP levels in baseline serum samples and genotyped five common CRP SNPs. Results Elevated CRP levels were associated with increased lung cancer risk (odds ratio [OR], 1.98; 95% CI, 1.35 to 2.89; P-trend < .001 for fourth quartile [Q4, ≥ 5.6 mg/L] v Q1 [< 1.0 mg/L]). The CRP association did not differ significantly by histology, follow-up time, or smoking status, but was most apparent for squamous cell carcinomas (OR, 2.92; 95% CI, 1.30 to 6.54), 2 to 5 years before lung cancer diagnosis (OR, 2.33; 95% CI, 1.24 to 4.39), and among former smokers (OR, 2.48; 95% CI, 1.53 to 4.03) and current smokers (OR, 1.90; 95% CI, 1.06 to 3.41). Although CRP SNPs and haplotypes were associated with CRP levels, they were not associated with lung cancer risk. Ten-year standardized absolute risks of lung cancer were higher with elevated CRP levels among former smokers (Q4: 2.55%; 95% CI, 1.98% to 3.27% v Q1: 1.39%; 95% CI, 1.07% to 1.81%) and current smokers (Q4: 7.37%; 95% CI, 5.81% to 9.33% v Q1: 4.03%; 95% CI, 3.01% to 5.40%). Conclusion Elevated CRP levels are associated with subsequently increased lung cancer risk, suggesting an etiologic role for chronic pulmonary inflammation in lung carcinogenesis.

scholarly journals Lung cancer risk from radon in Ontario, Canada: how many lung cancers can we prevent?

2013 ◽  
Vol 24 (11) ◽  
pp. 2013-2020 ◽  
Author(s):  
Emily Peterson ◽  
Amira Aker ◽  
JinHee Kim ◽  
Ye Li ◽  
Kevin Brand ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Lung Cancer Risk ◽  
Lung Cancers

scholarly journals The Associations of Fruit and Vegetable Intake with Lung Cancer Risk in Participants with Different Smoking Status: A Meta-Analysis of Prospective Cohort Studies

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1791 ◽  
Author(s):  
Chong Wang ◽  
Ting Yang ◽  
Xiao-fei Guo ◽  
Duo Li
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Dose Response ◽  
Lung Cancer Risk ◽  
Vegetable Intake ◽  
Smoking Status ◽  
Fruit And Vegetable Intake ◽  
Response Analysis ◽  
Prospective Cohort Studies ◽  
Former Smokers

The results of epidemiological studies on the relationship between fruit and vegetable intake and lung cancer risk were inconsistent among participants with different smoking status. The purpose of this study was to investigate these relationships in participants with different smoking status with prospective cohort studies. A systematic literature retrieval was conducted using PubMed and Scopus databases up to June 2019. The summary relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were calculated by random-effects model. The nonlinear dose-response analysis was carried out with restricted cubic spline regression model. Publication bias was estimated using Begg’s test. Nine independent prospective studies were included for data synthesis. Dietary consumption of fruit was negatively correlated with lung cancer risk among current smokers and former smokers, and the summery RRs were 0.86 (95% CI: 0.78, 0.94) and 0.91 (95% CI: 0.84, 0.99), respectively. Consumption of vegetable was significantly associated with reduced risk of lung cancer for current smokers (summary RR = 87%; 95% CI: 0.78, 0.94), but not for former smokers and never for smokers. Dose-response analysis suggested that risk of lung cancer was reduced by 5% (95% CI: 0.93, 0.97) in current smokers, and reduced by 4% (95% CI: 0.93, 0.98) in former smokers with an increase of 100 grams of fruit intake per day, respectively. Besides, dose-response analysis indicated a 3% reduction in lung cancer risk in current smokers for 100 gram per day increase of vegetable intake (95% CI: 0.96, 1.00). The findings of this study provide strong evidence that higher fruit consumption is negatively associated with the risk of lung cancer among current smokers and former smokers, while vegetable intake is significantly correlated with reducing the risk of lung cancer in current smokers. These findings might have considerable public health significance for the prevention of lung cancer through dietary interventions.

Lung Cancer Risk Reduction After Smoking Cessation: Observations From a Prospective Cohort of Women

2003 ◽  
Vol 21 (5) ◽  
pp. 921-926 ◽  
Author(s):  
J.O. Ebbert ◽  
P. Yang ◽  
C.M. Vachon ◽  
R.A. Vierkant ◽  
J.R. Cerhan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Smoking Cessation ◽  
Cancer Risk ◽  
Risk Reduction ◽  
Prospective Cohort ◽  
Lung Cancer Risk ◽  
Smoking History ◽  
Cox Regression Analysis ◽  
Former Smokers ◽  
Never Smokers

Purpose: We conducted this study because the duration of excess lung cancer risk among former smokers has been inconsistently reported, doubt has been raised regarding the population impact of smoking cessation, and differential risk reduction by histologic cell type after smoking cessation needs to be confirmed. Methods: The Iowa Women’s Health Study is a prospective cohort study of 41,836 Iowa women aged 55 to 69 years. In 1986, mailed questionnaires were used to collect detailed smoking history. Age-adjusted lung cancer incidence through 1999 was analyzed according to years of smoking abstinence. Relative risks were estimated using Cox regression analysis. Results: There were 37,078 women in the analytic cohort. Compared with the never smokers, former smokers had an elevated lung cancer risk (relative risk, 6.6; 95% confidence interval, 5.0 to 8.7) up to 30 years after smoking cessation for all former smokers. However, a beneficial effect of smoking cessation was observed among recent and distant former smokers. The risk of adenocarcinoma remained elevated up to 30 years for both former heavier and former lighter smokers. Conclusion: The risk for lung cancer is increased for both current and former smokers compared with never smokers and declines for former smokers with increasing duration of abstinence. The decline in excess lung cancer risk among former smokers is prolonged compared with other studies, especially for adenocarcinoma and for heavy smokers, suggesting that more emphasis should be placed on smoking prevention and lung cancer chemoprevention.

scholarly journals The impact of perceived risk, screening eligibility and worry on preference for lung cancer screening: a cross-sectional survey

2020 ◽  
Vol 6 (1) ◽  
pp. 00158-2019
Author(s):  
Katharine See ◽  
Renee Manser ◽  
Elyse R. Park ◽  
Daniel Steinfort ◽  
Bridget King ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Screening ◽  
Cancer Risk ◽  
Lung Cancer Risk ◽  
Lung Cancer Screening ◽  
Validated Questionnaire ◽  
Significant Difference ◽  
Perceived Seriousness ◽  
Former Smokers ◽  
The Impact

Lung cancer screening is effective at reducing lung cancer deaths when individuals at greatest risk are screened. Recruitment initiatives target all current and former smokers, of whom only some are eligible for screening, potentially leading to discordance between screening preference and eligibility in ineligible individuals. The objective of the present study was to identify factors associated with preference for screening among ever-smokers.Ever-smokers aged 55–80 years attending outpatient clinics at three Australian hospitals were invited. The survey recorded: 1) demographics; 2) objective lung cancer risk and screening eligibility using the Prostate Lung Colon Ovarian 2012 risk model; and 3) perceived lung cancer risk, worry about and seriousness of lung cancer using a validated questionnaire. Multivariable ordinal logistic regression identified predictors of screening preference.The survey was completed by 283 individuals (response rate 27%). Preference for screening was high (72%) with no significant difference between low-dose computed tomography screening-eligible and -ineligible individuals (77% versus 68%, p=0.11). Worry about lung cancer (adjusted-proportional odds ratio (adj-OR) 1.31, 95% CI 1.08–1.58; p=0.007) and perceived seriousness of lung cancer (adj-OR 1.31, 95% CI 1.05–1.64; p=0.02) were associated with higher preference for lung cancer screening while screening eligibility was not. The concept of “early detection” was the most important driver to have screening while practical obstacles like difficulty travelling to the scan or taking time off work were the least important barriers to screening.Most current or former smokers prefer to undergo screening. Worry about lung cancer and perceived seriousness of the diagnosis are more important drivers for screening preference than eligibility status.

Active and passive smoking in relation to lung cancer incidence in the Women's Health Initiative prospective cohort study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1504-1504
Author(s):  
Ange Wang ◽  
Jessica Kubo ◽  
Juhua Luo ◽  
Manisha Desai ◽  
Michael T Henderson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Cancer Incidence ◽  
Passive Smoking ◽  
Prospective Cohort ◽  
Lung Cancer Risk ◽  
Lung Cancer Incidence ◽  
Cancer Subtypes ◽  
Former Smokers ◽  
Never Smokers

1504 Background: The relationship between both active and passive smoking and lung cancer incidence in post-menopausal women was examined in theWomen’s Health Initiative Observational Study (WHI-OS). Methods: The WHI-OS, a prospective cohort study conducted at 40 U.S. centers, enrolled women ages 50-79 from 1993-1998.Among 93,676 participants, 76,304 women with complete smoking and covariate data comprised the analytic cohort, in which the association of lung cancer incidence with active and passive (childhood, adult home, and work) smoking exposure was studied. Results: Over 10.5 meanyears of follow-up with 901 lung cancer cases, lung cancer incidence was higher in current smokers (HR 13.44, 95% CI 10.80-16.75) and former smokers (HR 4.20, 95% CI 3.48-5.08), compared to never smokers. This relationship was dose-dependent for both current and former smokers. Risk of all lung cancer subtypes, particularly small cell lung cancer (SCLC) and squamous cell carcinoma (SqCC), was higher in smokers. Among never smokers, any passive smoking exposure (HR 0.88, 95% CI 0.52-1.49) and most passive smoking categories did not significantly increase lung cancer risk, compared to no passive exposure; however, passive exposure as an adult at home for >=30 years was associated with increased risk, of borderline significance (HR 1.61, 95% CI 1.00-2.58). Current smokers had an annualized lung cancer incidence rate of 472.9 cases/100,000 person-years, compared to 158.1 for former smokers and 36.2 for never smokers (112.3 overall). Conclusions: To our knowledge, this is the first study to examine both active and passive smoking in relation to lung cancer incidence in a complete prospective cohort of U.S. women. Active smoking is associated with significant increases in incidence of all lung cancer subtypes in post-menopausal women, particularly SCLC and SqCC. Smoking cessation decreases lung cancer risk. Prolonged exposure as an adult at home may be the strongest passive smoking contributor to lung cancer risk in this cohort. The findings support continued need for investment in smoking prevention and cessation, research on passive smoking, and understanding of lung cancer risk factors other than smoking.

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