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

By R. Huang, Y. Wei, R.J. Hung, G. Liu, L. Su, R. Zhang, X. Zong, Z.F. Zhang, H. Morgenstern, I. Brüske, J. Heinrich, Y.C. Hong, J.H. Kim, M. Cote, A. Wenzlaff, A.G. Schwartz, I. Stucker, J. Mclaughlin, M.W. Marcus, M.P. Davies, T. Liloglou, J.K. Field, K. Matsuo, M. Barnett, M. Thornquist, G. Goodman, Y. Wang, S. Chen, P. Yang, E.J. Duell, A.S. Andrew, P. Lazarus, J. Muscat, P. Woll, J. Horsman, M. Dawn Teare, A. Flugelman, G. Rennert, Y. Zhang, H. Brenner, C. Stegmaier, E.H. van der Heijden, K. Aben, L. Kiemeney, J. Barros-Dios, M. Pérez-Ríos, A. Ruano-Ravina, N.E. Caporaso, P.A. Bertazzi, M.T. Landi, J. Dai, H. Shen, G. Fernandez-Tardon, M. Rodriguez-Suarez, A. Tardon and D.C. Christiani


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. Abbreviations COPD, chronic obstructive pulmonary disease; CPG, cigarettes per day; ILCCO, International Lung Cancer Consortium; MeSH, medical subject headings; NSCLC, non-small cell lung cancer; OR, odds ratio; SCLC, small cell lung cancer

Publisher: 'Elsevier BV'
Year: 2015
DOI identifier: 10.1016/j.ebiom.2015.09.031
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