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O06 - Cancer Control and Epidemiology I (ID 135)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Prevention & Epidemiology
- Presentations: 1
O06.06 - Factors Associated with Smoking Cessation in Participants of The Pan Canadian Early Lung Cancer Study (ID 1469)
10:30 - 12:00 | Author(s): J.C. English
Lung cancer screening programs provide unique opportunities to facilitate smoking cessation in smokers who participate in these programs. However, the effects of screening on motivation to quit might be mediated or modified by other variables. Identifying the participants more likely to quit will allow rapid application of smoking cessation resources to these participants, while those least likely to quit can be afforded experimental interventions. The aim of our study was to assess the impact of lung cancer screening on smoking cessation in current smokers at the time of enrollment and to identify factors that were associated with quitting smoking in this screening population.
Using data collected from the Pan-Canadian Study of Early Detection of Lung Cancer, both univariate and multivariable logistic regression analysis was used to identify predictors of smoking cessation among current smokers at enrolment. Smoking cessation was defined as quitting for at least a 6 month period, occurring anytime after enrolment.
We analyzed baseline and follow-up questionnaires of 2320 participants, of which 1419 were current smokers. Of these 1419 patients, 392 (27.8%) met the definition of smoking cessation during a median of two annual follow-up visits. In both univariate and multivariable (MV) analysis, greater smoking cessation was associated with four factors: (i) having a diagnosis of lung cancer at any time during the screening process, with a MV Odds ratio (OR) of quitting of 2.4 (95%CI: 1.1-5.0); (ii) lower and medium nicotine addiction as assessed by the Fagerström Nicotine Dependence Scale Score, with MV-ORs of 3.2 (95%CI: 2.2-4.6) and 1.4 (95%CI: 0.9-2.0), respectively; (iii) having higher education, with MV-OR: 1.4 (95%CI: 1.1-1.9); and (iv) having an earlier age of onset of regular alcohol intake, with MV-OR of 1.11 (95%CI: 1.02-1.21) per 5 year decrease in age. Smoking cessation was also associated with (i) previous attempts of quitting [UV-OR 1.8 (95%CI: 1.2-2.7)], willingness to quit smoking within the next month (at baseline screening) [UV-OR 2.2 (95%CI: 1.8-2.9)] or within the next 6 months after baseline screening [UV-OR 1.8 (95%CI: 1.3.-2.4)]. Second-hand smoking exposure, including exposure as a child, or as an adult at work, at home, privately with friends, or in public settings, or a cumulative index of these different exposures, was not associated with smoking cessation. Presence of potential index symptoms for lung disease, including shortness of breath, cough (both dry and productive), hoarseness, audible wheezing or even chest pain, was not associated with an increased chance of smoking cessation.
The diagnosis of a new lung cancer had a major positive impact on screening participants quitting smoking, as were factors such as lower nicotine dependence, higher education, earlier starting alcohol drinking age, and willingness to quit. Whether a new lung cancer diagnosis triggered additional efforts by clinicians to help the person quit will be explored further. Individual lung symptoms and secondhand smoke exposure were not associated with smoking cessation. (Geoffrey Liu and Martin Tamemmagi are co-senior authors)
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P1.02 - Poster Session 1 - Novel Cancer Genes and Pathways (ID 144)
- Event: WCLC 2013
- Type: Poster Session
- Track: Biology
- Presentations: 1
- Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
P1.02-004 - Differential pathway disruption in lung adenocarcinomas from current and never smokers - A multi-omics data integration analysis (ID 1072)
09:30 - 16:30 | Author(s): J.C. English
Lung cancers in smokers and never smokers (NS) are distinct clinical diseases. Specific molecular differences identified in these two groups include: EGFR and KRAS mutation, DNA methylation levels at specific loci, and most recently, global mutation spectra. However, much remains to be understood about the biology driving lung tumourigenesis in smokers and NS in order to improve treatment outcome. To date, no multi-dimensional integrative genomics (i.e. multi-omics) analysis designed to specifically compare current (CS) and NS lung tumours has been performed. We hypothesize that a multi-omics analysis which considers each tumour as its own unique perturbed system (as opposed to a grouped approach) will reveal molecular mechanisms of lung adenocarcinoma (AC) biology that are common or different in CS and NS.
Copy number, DNA methylation, and gene expression profiles were generated for lung AC and matched non-malignant lung tissues from 34 CS and 30 NS. PCR was performed to determine EGFR and KRAS mutation status. Copy number, methylation and expression alterations were integrated for 14,000 genes on an individual tumour basis. Disrupted genes were ranked according to the magnitude of alterations they exhibited using a novel algorithm we developed denoted MITRA. Of the genes scored by MITRA, those ranking in the 99th and 1st (top) percentiles for up- and downregulation, respectively, were subjected to Ingenuity Pathway Analysis (IPA). IPA was performed separately on all 64 lung tumours and pathway results for CS and NS were compared.
We identified 361 genes that ranked in the top percentiles for up- or downregulation in at least 20% of the lung ACs we assessed. Identification of recurrent RASSF1A downregulation, and EGFR upregulation predominantly in NS demonstrates the ability of our ranking algorithm to prioritize genes known to be involved in lung tumour biology using multi-dimensional genomics data. To determine cellular pathways and functions likely deregulated as a consequence of gene disruption, we performed IPA on each tumour and determined the frequency of individual pathway disruption across tumours. This analysis revealed 88 annotated pathways with a minimum disruption frequency of 15% in either or both CS and NS. Commonly affected pathways involved: adhesion and extravasation implicating tumour invasion and migration; various catabolic and anabolic processes implicating cell metabolism; and several specific signaling pathways including atherosclerosis and Wnt/β-catenin signaling implicating inflammation and cell proliferation. Comparison of the pathways identified in CS and NS revealed 13 differentially disrupted pathways (Fisher's Exact test p < 0.05 and disruption frequency difference > 15%). Eleven pathways were preferentially disrupted in CS and affected metabolic, immune response, and inflammatory pathways. Anandamine degradation and ephrin receptor signaling were preferential to NS.
Our novel, multi-omics tumour system based approach revealed genes prominently disrupted in CS and NS lung AC which were associated with several cellular pathways commonly or differentially disrupted in these two groups. Pathways affected by genes disrupted at both the DNA and RNA level may contribute to the distinct clinical characteristics associated with CS and NS lung cancer and may serve as targets for intervention.