Associated Links Among Smoking, Chronic Obstructive Pulmonary Disease, and Small Cell Lung Cancer: A Pooled Analysis in the International Lung Cancer Consortium

Ruyi Huang, Yongyue Wei, Rayjean J. Hung, Geoffrey Liu, Li Su, Ruyang Zhang, Xuchen Zong, Zuo Feng Zhang, Hal Morgenstern, Irene Brüske, Joachim Heinrich, Yun Chul Hong, Jin Hee Kim, Michele Cote, Angela Wenzlaff, Ann G. Schwartz, Isabelle Stucker, John Mclaughlin, Michael W. Marcus, Michael P.A. DaviesTriantafillos Liloglou, John K. Field, Keitaro Matsuo, Matt Barnett, Mark Thornquist, Gary Goodman, Yi Wang, Size Chen, Ping Yang, Eric J. Duell, Angeline S. Andrew, Philip Lazarus, Joshua Muscat, Penella Woll, Janet Horsman, M. Dawn Teare, Anath Flugelman, Gad Rennert, Yan Zhang, Hermann Brenner, Christa Stegmaier, Erik H.F.M. van der Heijden, Katja Aben, Lambertus Kiemeney, Juan Barros-Dios, Monica Pérez-Ríos, Alberto Ruano-Ravina, Neil E. Caporaso, Pier Alberto Bertazzi, Maria Teresa Landi, Juncheng Dai, Hongbing Shen, Guillermo Fernandez-Tardon, Marta Rodriguez-Suarez, Adonina Tardon, David C. Christiani

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


Background: The high relapse and mortality rate of small-cell lung cancer (SCLC) fuels the need for epidemiologic study to aid in its prevention. Methods: We included 24 studies from the ILCCO collaboration. Random-effects panel logistic regression and cubic spline regression were used to estimate the effects of smoking behaviors on SCLC risk and explore their non-linearity. Further, we explored whether the risk of smoking on SCLC was mediated through COPD. Findings: Significant dose-response relationships of SCLC risk were observed for all quantitative smoking variables. Smoking pack-years were associated with a sharper increase of SCLC risk for pack-years ranged 0 to approximately 50. The former smokers with longer cessation showed a 43%quit_for_5-9 years to 89%quit_for_≥20 years declined SCLC risk vs. subjectswho had quit smoking <5 years. Compared with non-COPD subjects, smoking behaviors showed a significantly higher effect on SCLC risk among COPD subjects, and further, COPD patients showed a 1.86-fold higher risk of SCLC. Furthermore, smoking behaviors on SCLC riskwere significantlymediated through COPD which accounted for 0.70% to 7.55% of total effects. Interpretation: This is the largest pooling study that provides improved understanding of smoking on SCLC, and further demonstrates a causal pathway through COPD that warrants further experimental study.

Original languageEnglish (US)
Pages (from-to)1677-1685
Number of pages9
Issue number11
StatePublished - Nov 1 2015

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology


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