scholarly journals AHRR methylation in heavy smokers: associations with smoking, lung cancer risk, and lung cancer mortality

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Laurie Grieshober ◽  
Stefan Graw ◽  
Matt J. Barnett ◽  
Mark D. Thornquist ◽  
Gary E. Goodman ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Screening ◽  
Cancer Risk ◽  
Lung Cancer Risk ◽  
Conditional Logistic Regression ◽  
Asbestos Exposure ◽  
Lung Cancer Screening ◽  
Cox Proportional Hazards ◽  
Small Cell ◽  
Heavy Smokers

Abstract Background A low level of methylation at cg05575921 in the aryl-hydrocarbon receptor repressor (AHRR) gene is robustly associated with smoking, and some studies have observed associations between cg05575921 methylation and increased lung cancer risk and mortality. To prospectively examine whether decreased methylation at cg05575921 may identify high risk subpopulations for lung cancer screening among heavy smokers, and mortality in cases, we evaluated associations between cg05575921 methylation and lung cancer risk and mortality, by histotype, in heavy smokers. Methods The β-Carotene and Retinol Efficacy Trial (CARET) included enrollees ages 45–69 with ≥ 20 pack-year smoking histories and/or occupational asbestos exposure. A subset of CARET participants had cg05575921 methylation available from HumanMethylationEPIC assays of blood collected on average 4.3 years prior to lung cancer diagnosis in cases. Cg05575921 methylation β-values were treated continuously for a 10% methylation decrease and as quintiles, where quintile 1 (Q1, referent) represents high methylation and Q5, low methylation. We used conditional logistic regression models to examine lung cancer risk overall and by histotype in a nested case-control study including 316 lung cancer cases (diagnosed through 2005) and 316 lung cancer-free controls matched on age (±5 years), sex, race/ethnicity, enrollment year, current/former smoking, asbestos exposure, and follow-up time. Mortality analyses included 372 lung cancer cases diagnosed between 1985 and 2013 with available methylation data. We used Cox proportional hazards models to examine mortality overall and by histotype. Results Decreased cg05575921 methylation was strongly associated with smoking, even in our population of heavy smokers. We did not observe associations between decreased pre-diagnosis cg05575921 methylation and increased lung cancer risk, overall or by histotype. We observed linear increasing trends for lung cancer-specific mortality across decreasing cg05575921 methylation quintiles for adenocarcinoma and small cell carcinoma (P-trends = 0.01 and 0.04, respectively). Conclusions In our study of heavy smokers, decreased cg05575921 methylation was strongly associated with smoking but not increased lung cancer risk. The observed association between cg05575921 methylation and increased mortality in adenocarcinoma and small cell histotypes requires further examination. Our results do not support using decreased cg05575921 methylation as a biomarker for lung cancer screening risk stratification.

scholarly journals Incorporating Both Genetic and Tobacco Smoking Data to Identify High-Risk Smokers for Lung Cancer Screening

2021 ◽  
Author(s):  
Guochong Jia ◽  
Wanqing Wen ◽  
Pierre P Massion ◽  
Xiao-Ou Shu ◽  
Wei Zheng
Keyword(s):  
Lung Cancer ◽  
Cancer Screening ◽  
High Risk ◽  
Cancer Risk ◽  
Tobacco Smoking ◽  
Lung Cancer Risk ◽  
Lung Cancer Screening ◽  
Heavy Smoker ◽  
Polygenic Risk Score ◽  
Heavy Smokers

Abstract The U.S. Preventive Services Task Force (USPSTF) recently proposed to widen the current lung cancer screening guideline to include less-heavy smokers. We sought to incorporate both genetic and tobacco smoking data to evaluate the proposed new guideline in white smokers. We constructed a polygenic risk score (PRS) using lung cancer risk variants. Using data from 308,490 participants of European descent in the UK Biobank, a population-based cohort study, we estimated hazard ratios (HRs) of lung cancer associated with both tobacco smoking and PRS to identify individuals at a similar or higher risk than the group of heavy smokers who are recommended for screening under the USPSTF-2014 guideline (≥30 pack-years, either current or former smokers who quit within 15 years). During a median follow-up of 5.8 years, 1,449 incident cases of lung cancer were identified. We found a similar lung cancer risk for current smokers with 20-29 pack-years (HR=20.7, 95% confidence interval (CI): 16.3-26.4) and the “heavy smoker group” defined above (HR=19.9, 95% CI: 16.8-23.6) compared with never smokers. Current smokers with 20-29 pack-years did not reach a 6-year absolute risk of 0.0151, a suggested risk threshold for using low-dose computed tomography screening, until the age of 55 years. However, these smokers at high genetic risk (PRS ≥80%) reached this risk level at the age of 50. Our findings support the USPSTF proposal to lower the smoking pack-year eligibility to 20 pack-years for current smokers and suggest that PRS for lung cancer could be considered to identify high-risk smokers for screening.

scholarly journals What is the effect of a decision aid on knowledge, values and preferences for lung cancer screening? An online pre–post study

BMJ Open ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. e045160
Author(s):  
Stephen D Clark ◽  
Daniel S Reuland ◽  
Alison T Brenner ◽  
Michael P Pignone
Keyword(s):  
Lung Cancer ◽  
Cancer Screening ◽  
Cancer Risk ◽  
Decision Aid ◽  
Lung Cancer Risk ◽  
Lung Cancer Screening ◽  
False Positives ◽  
Substantial Proportion ◽  
College Degree ◽  
Out Of Pocket Costs

ObjectiveTo examine if a decision aid improves knowledge of lung cancer screening benefits and harms and which benefits and harms are most valued.DesignPre–post study.SettingOnline.Participants219 current or former (quit within the previous 15 years) smokers ages 55–80 with at least 30 pack-years of smoking.InterventionLung cancer screening video decision aid.Main measuresScreening knowledge tested by 10 pre–post questions and value of benefits and harms (reducing chance of death from lung cancer, risk of being diagnosed, false positives, biopsies, complications of biopsies and out-of-pocket costs) assessed through rating (1–5 scale) and ranking (top three ranked).ResultsMean age was 64.7±6.1, 42.5% were male, 75.4% white, 48.4% married, 28.9% with less than a college degree and 67.6% with income <US$50 000. Knowledge improved postdecision aid (pre 2.8±1.8 vs post 5.8±2.3, diff +3.0, 95% CI 2.7 to 3.3; p<0.001). For values, reducing the chance of death from lung cancer was rated and ranked highest overall (rating 4.3±1.0; 59.4% ranked first). Among harms, avoiding complications (3.7±1.3) and out-of-pocket costs (3.7±1.2) rated highest. Thirty-four per cent ranked one of four harms highest: avoiding costs 13.2%, false positives 7.3%, biopsies 7.3%, complications 5.9%. Screening intent was balanced (1–4 scale; 1-not likely 21.0%, 4-very likely 26.9%). Those ‘not likely’ to screen had greater improvement in pre–post knowledge scores and more frequently ranked a harm first than those ‘very likely’ to screen (pre–post diff:+3.5 vs +2.6, diff +0.9; 95% CI 0.1 to 1.8; p=0.023; one of four harms ranked first: 28.4% vs 11.3%, p<0.001).ConclusionsOur decision aid increased lung cancer screening knowledge among a diverse sample of screen-eligible respondents. Although a majority valued ‘reducing the chance of death from lung cancer’ highest, a substantial proportion identified harms as most important. Knowledge improvement and ranking harms highest were associated with lower intention to screen.

scholarly journals Perspectives of family physicians towards access to lung cancer screening for individuals living with low income – a qualitative study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ambreen Sayani ◽  
Mandana Vahabi ◽  
Mary Ann O’Brien ◽  
Geoffrey Liu ◽  
Stephen W. Hwang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Health Care ◽  
Cancer Screening ◽  
Cancer Risk ◽  
Low Income ◽  
Lung Cancer Risk ◽  
Family Physicians ◽  
Lung Cancer Screening ◽  
Preventative Care ◽  
Systems Model

Abstract Background Individuals living with low income are less likely to participate in lung cancer screening (LCS) with low-dose computed tomography. Family physicians (FPs) are typically responsible for referring eligible patients to LCS; therefore, we sought to understand their perspectives on access to lung cancer screening for individuals living with low income in order to improve equity in access to LCS. Methods A theory-informed thematic analysis was conducted using data collected from 11 semi-structured interviews with FPs recruited from three primary care sites in downtown Toronto. Data was coded using the Systems Model of Clinical Preventative Care as a framework and interpretation was guided by the synergies of oppression analytical lens. Results Four overarching themes describe FP perspectives on access to LCS for individuals living with low income: the degree of social disadvantage that influences lung cancer risk and opportunities to access care; the clinical encounter, where there is often a mismatch between the complex health needs of low income individuals and structure of health care appointments; the need for equity-oriented health care, illustrated by the neglect of structural origins of health risk and the benefits of a trauma-informed approach; and finally, the multiprong strategies that will be needed in order to improve equity in health outcomes. Conclusion An equity-oriented and interdisciplinary team based approach to care will be needed in order to improve access to LCS, and attention must be given to the upstream determinants of lung cancer in order to reduce lung cancer risk.

Predictive Accuracy of the PanCan Lung Cancer Risk Prediction Model -External Validation based on CT from the Danish Lung Cancer Screening Trial

2015 ◽  
Vol 25 (10) ◽  
pp. 3093-3099 ◽  
Author(s):  
Mathilde M. Winkler Wille ◽  
Sarah J. van Riel ◽  
Zaigham Saghir ◽  
Asger Dirksen ◽  
Jesper Holst Pedersen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Screening ◽  
Cancer Risk ◽  
Prediction Model ◽  
Lung Cancer Risk ◽  
Predictive Accuracy ◽  
External Validation ◽  
Lung Cancer Screening ◽  
Cancer Screening Trial ◽  
Screening Trial

scholarly journals Individual 5-Year Lung Cancer Risk Prediction Model in Korea Using a Nationwide Representative Database

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3496
Author(s):  
Yohwan Yeo ◽  
Dong Wook Shin ◽  
Kyungdo Han ◽  
Sang Hyun Park ◽  
Keun-Hye Jeon ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Screening ◽  
Cancer Risk ◽  
Prediction Model ◽  
Risk Prediction ◽  
Lung Cancer Risk ◽  
Lung Cancer Screening ◽  
Risk Prediction Model ◽  
C Statistic ◽  
The Mean

Early detection of lung cancer by screening has contributed to reduce lung cancer mortality. Identifying high risk subjects for lung cancer is necessary to maximize the benefits and minimize the harms followed by lung cancer screening. In the present study, individual lung cancer risk in Korea was presented using a risk prediction model. Participants who completed health examinations in 2009 based on the Korean National Health Insurance (KNHI) database (DB) were eligible for the present study. Risk scores were assigned based on the adjusted hazard ratio (HR), and the standardized points for each risk factor were calculated to be proportional to the b coefficients. Model discrimination was assessed using the concordance statistic (c-statistic), and calibration ability assessed by plotting the mean predicted probability against the mean observed probability of lung cancer. Among candidate predictors, age, sex, smoking intensity, body mass index (BMI), presence of chronic obstructive pulmonary disease (COPD), pulmonary tuberculosis (TB), and type 2 diabetes mellitus (DM) were finally included. Our risk prediction model showed good discrimination (c-statistic, 0.810; 95% CI: 0.801–0.819). The relationship between model-predicted and actual lung cancer development correlated well in the calibration plot. When using easily accessible and modifiable risk factors, this model can help individuals make decisions regarding lung cancer screening or lifestyle modification, including smoking cessation.

scholarly journals Association of Race With Lung Cancer Risk Among Adults Undergoing Lung Cancer Screening

2021 ◽  
Vol 4 (4) ◽  
pp. e214509
Author(s):  
Christine S. Shusted ◽  
Nathaniel R. Evans ◽  
Hee-Soon Juon ◽  
Gregory C. Kane ◽  
Julie A. Barta
Keyword(s):  
Lung Cancer ◽  
Cancer Screening ◽  
Cancer Risk ◽  
Lung Cancer Risk ◽  
Lung Cancer Screening

scholarly journals Perspectives of family physicians towards access to lung cancer screening for individuals living with low income – a qualitative study

2020 ◽  
Author(s):  
Ambreen Sayani ◽  
Mandana Vahabi ◽  
Mary Ann O’Brien ◽  
Geoffrey Liu ◽  
Stephen W. Hwang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Health Care ◽  
Cancer Screening ◽  
Cancer Risk ◽  
Low Income ◽  
Lung Cancer Risk ◽  
Family Physicians ◽  
Lung Cancer Screening ◽  
Preventative Care ◽  
Systems Model

Abstract Background: Individuals living with low income are less likely to participate in lung cancer screening (LCS) with low-dose computed tomography. Family physicians (FPs) are typically responsible for referring eligible patients to LCS; therefore, we sought to understand their perspectives on access to lung cancer screening for individuals living with low income in order to improve equity in access to LCS. Methods: A theory-informed thematic analysis was conducted using data collected from 11 semi-structured interviews with FPs recruited from three primary care sites in downtown Toronto. Data was coded using the Systems Model of Clinical Preventative Care as a framework and interpretation was guided by the synergies of oppression analytical lens. Results: Four overarching themes describe FP perspectives on access to LCS for individuals living with low income: the degree of social disadvantage that influences lung cancer risk and opportunities to access care; the clinical encounter, where there is often a mismatch between the complex health needs of low income individuals and structure of health care appointments; the need for equity-oriented health care, illustrated by the neglect of structural origins of health risk and the benefits of a trauma-informed approach; and finally, the multiprong strategies that will be needed in order to improve equity in health outcomes. Conclusion: An equity-oriented and interdisciplinary team based approach to care will be needed in order to improve access to LCS, and attention must be given to the upstream determinants of lung cancer in order to reduce lung cancer risk.

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