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 Hongbing Shen, Guillermo Fernandez-Tardon, Marta Rodriguez-Suarez, Adonina Tardon, David C Christiani

Research output: Contribution to journalArticle (journal)peer-review

52 Citations (Scopus)


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. subjects who 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 risk were significantly mediated 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
Pages (from-to)1677-85
Number of pages9
Issue number11
Publication statusPublished - Nov 2015


  • Aged
  • Case-Control Studies
  • Female
  • Humans
  • Lung Neoplasms/epidemiology
  • Male
  • Middle Aged
  • Models, Biological
  • Odds Ratio
  • Population Surveillance
  • Pulmonary Disease, Chronic Obstructive/complications
  • Risk
  • Small Cell Lung Carcinoma/epidemiology
  • Smoking/adverse effects
  • Time Factors


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