Cigarette smoking increases copy number alterations in nonsmall-cell lung cancer

Huang, Yen‐Tsung; Lin, Xihong; Liu, Yan; Chirieac, Lucian R.; McGovern, Ray; Wain, John C.; Heist, Rebecca S.; Skaug, Vidar; Zienolddiny, Shanbeh; Haugen, Aage; Su, Li; Fox, Edward A.; Wong, Kwok-Kin; Christiani, David C.

doi:10.1073/pnas.1102769108

Cited by 54 publications

(61 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Different cohort characteristics could therefore be an important explanation for the observed differences in amount of CNAs in smoking-defined subgroups between individual cohorts in the current study (Fig. 2), but also between previous studies reporting contradicting results (12,14,15). In addition, the smoking group definitions themselves are a source of variation due to their self-reported nature and potentially different definitions between studies.…”

Section: Discussioncontrasting

confidence: 40%

Section: Discussionmentioning

confidence: 99%

“…Previous studies reporting overall more CNAs in smokers (14,15), and more CNAs in heavy compared with light smokers (based on pack-years, a composite index of smoking intensity and duration; ref. 14), have included a notable fraction of squamous cell carcinomas (predominantly smokers). Importantly, squamous cell lung carcinoma has been shown to harbor overall more, as well as specific, CNAs compared with adenocarcinomas (30), which could influence these results.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, conflicting reports exist on whether smokers overall display more or less copy-number alterations (CNAs) than never-smokers (12,14,15). Together, this indicates a significant heterogeneity within smoking-defined subgroups of adenocarcinoma.…”

Section: Introductionmentioning

confidence: 95%

See 3 more Smart Citations

Genomic and Transcriptional Alterations in Lung Adenocarcinoma in Relation to Smoking History

Karlsson

Ringnér

Lauss

et al. 2014

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Cigarette smoking is the major pathogenic factor for lung cancer. The precise mechanisms of tobacco-related carcinogenesis and its effect on the genomic and transcriptional landscape in lung cancer are not fully understood.Experimental Design: A total of 1,398 (277 never-smokers and 1,121 smokers) genomic and 1,449 (370 never-smokers and 1,079 smokers) transcriptional profiles were assembled from public lung adenocarcinoma cohorts, including matched next-generation DNA-sequencing data (n ¼ 423). Unsupervised and supervised methods were used to identify smoking-related copy-number alterations (CNAs), predictors of smoking status, and molecular subgroups.Results: Genomic meta-analyses showed that never-smokers and smokers harbored a similar frequency of total CNAs, although specific regions (5q, 8q, 16p, 19p, and 22q) displayed a 20% to 30% frequency difference between the two groups. Importantly, supervised classification analyses based on CNAs or gene expression could not accurately predict smoking status (balanced accuracies 60% to 80%). However, unsupervised multicohort transcriptional profiling stratified adenocarcinomas into distinct molecular subgroups with specific patterns of CNAs, oncogenic mutations, and mutation transversion frequencies that were independent of the smoking status. One subgroup included approximately 55% to 90% of neversmokers and approximately 20% to 40% of smokers (both current and former) with molecular and clinical features of a less aggressive and smoking-unrelated disease. Given the considerable intragroup heterogeneity in smoking-defined subgroups, especially among former smokers, our results emphasize the clinical importance of accurate molecular characterization of lung adenocarcinoma.Conclusions: The landscape of smoking-related CNAs and transcriptional alterations in adenocarcinomas is complex, heterogeneous, and with moderate differences. Our results support a molecularly distinct less aggressive adenocarcinoma entity, arising in never-smokers and a subset of smokers. Clin Cancer Res; 20(18); 4912-24. Ó2014 AACR.

show abstract

Section: Discussioncontrasting

confidence: 40%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

See 2 more Smart Citations

Genomic and Transcriptional Alterations in Lung Adenocarcinoma in Relation to Smoking History

Karlsson

Ringnér

Lauss

et al. 2014

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…In addition to tobacco, environmental/ occupational exposures, combined with inherited susceptibility variants, may impact carcinogen metabolism or inflammatory processes to modulate risk among smokers (11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Prospective evaluation of C-reactive protein, smoking and lung cancer death in the Third National Health and Nutrition Examination Survey

Bittoni

Focht

Clinton

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

Abstract.Chronic inflammation plays an important role in lung carcinogenesis. Few prospective studies have examined associations between lung cancer, serum C-reactive protein (CRP), a measure of systemic inflammation, and inflammatory lifestyle factors, such as smoking and obesity. This study prospectively examined the relationship between CRP and lung cancer death and its interrelationships with several lifestyle factors. Baseline data on smoking and other lifestyle variables were collected for 8,950 participants in the Third National Health and Nutrition Examination Survey (NHANES III: 1988-1994. Baseline CRP levels were measured in serum samples by nephelometry. Mortality status was ascertained through probabilistic record matching using the National Death Index through 2006. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) for CRP and lung cancer death, with adjustment for smoking and other variables. During 18 years of follow-up, 219 individuals died from lung cancer. Multivariate regression models revealed a dose-response effect for elevated CRP and risk of lung cancer death when adjusting for age, gender, BMI and smoking. Compared to individuals with CRP <3 mg/l, lung cancer death was significantly associated with elevated levels of CRP: HR=1.63 (95% CI=1.15-2.26) for 3-7 mg/l and HR=2.44 (95% CI=1.81-3.45) for CRP >7 mg/l, P-trend <0.0001). The risk of lung cancer death for smokers increased 9-fold in adjusted models (P<0.0001). When stratified by gender and smoking status the effects of CRP were similar for smokers and males but did not reach statistical significance for females and non-smokers. This study supports a dose-dependent relationship between lung cancer death and CRP for males and smokers, but additional efforts are needed to better elucidate these relationships in women and non-smokers. The results suggest that CRP may emerge as a valuable tool in identifying high-risk subgroups of smokers for lung cancer prevention strategies.

show abstract

Epigenetic–smoking interaction reveals histologically heterogeneous effects of TRIM27 DNA methylation on overall survival among early‐stage NSCLC patients

Lin

Shen

et al. 2020

Molecular Oncology

Self Cite

View full text Add to dashboard Cite

Tripartite motif containing 27 (TRIM27) is highly expressed in lung cancer, including non-small-cell lung cancer (NSCLC). Here, we profiled DNA methylation of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tumours from 613 early-stage NSCLC patients and evaluated associations between CpG methylation of TRIM27 and overall survival. Significant CpG probes were confirmed in 617 samples from The Cancer Genome Atlas. The methylation of the CpG probe cg05293407 TRIM27 was significantly associated with overall survival in patients with LUSC (HR = 1.65, 95% CI: 1.30-2.09, P = 4.52 9 10 À5), but not in patients with LUAD (HR = 1.08, 95% CI: 0.87-1.33, P = 0.493). As incidence of LUSC is associated with higher smoking intensity compared to LUAD, we investigated whether smoking intensity impacted on the prognostic effect of cg05293407 TRIM27 methylation in NSCLC. LUSC patients had a higher average pack-year of smoking

show abstract

Cigarette smoking increases copy number alterations in nonsmall-cell lung cancer

Cited by 54 publications

References 31 publications

Genomic and Transcriptional Alterations in Lung Adenocarcinoma in Relation to Smoking History

Genomic and Transcriptional Alterations in Lung Adenocarcinoma in Relation to Smoking History

Prospective evaluation of C-reactive protein, smoking and lung cancer death in the Third National Health and Nutrition Examination Survey

Epigenetic–smoking interaction reveals histologically heterogeneous effects of TRIM27 DNA methylation on overall survival among early‐stage NSCLC patients

Contact Info

Product

Resources

About