Elevated platelet count appears to be causally associated with increased risk of lung cancer: A mendelian randomization analysis

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Ying Zhu, Yongyue Wei, Ruyang Zhang, Xuesi Dong, Sipeng Shen, Yang Zhao, Jianling Bai, Demetrius Albanes, Neil E. Caporaso, Maria Teresa Landi, Bin Zhu, Stephen J. Chanock, Fangyi Gu, Stephen Lam, Ming Sound Tsao, Frances A. Shepherd, Adonina Tardon, Ana Fernandez-Somoano, Guillermo Fernandez-Tardon, Chu Chen & 57 more Matthew J. Barnett, Jennifer Doherty, Stig E. Bojesen, Mattias Johansson, Paul Brennan, James D. McKay, Robert Carreras-Torres, Thomas Muley, Angela Risch, Heunz Erich Wichmann, Heike Bickeboeller, Albert Rosenberger, Gad Rennert, Walid Saliba, Susanne M. Arnold, John K. Field, Michael P.A. Davies, Michael W. Marcus, Xifeng Wu, Yuanqing Ye, Loic Le Marchand, Lynne R. Wilkens, Olle Melander, Jonas Manjer, Hans Brunnstrom, Rayjean J. Hung, Geoffrey Liu, Yonathan Brhane, Linda Kachuri, Angeline S. Andrew, Eric J. Duell, Lambertus A. Kiemeney, Erik H.F.M. Van der Heijden, Aage Haugen, Shanbeh Zienolddiny, Vidar Skaug, Kjell Grankvist, Mikael Johansson, Penella J. Woll, Angela Cox, Fiona Taylor, Dawn M. Teare, Philip Lazarus, Matthew B. Schabath, Melinda C. Aldrich, Richard S. Houlston, John McLaughlin, Victoria L. Stevens, Hongbing Shen, Zhibin Hu, Juncheng Dai, Christopher I. Amos, Younghun Han, Dakai Zhu, Gary E. Goodman, Feng Chen, David C. Christiani

Background: Platelets are a critical element in coagulation and inflammation, and activated platelets are linked to cancer risk through diverse mechanisms. However, a causal relationship between platelets and risk of lung cancer remains unclear. Methods: We performed single and combined multiple instrumental variable Mendelian randomization analysis by an inverse-weighted method, in addition to a series of sensitivity analyses. Summary data for associations between SNPs and platelet count are from a recent publication that included 48,666 Caucasian Europeans, and the International Lung Cancer Consortium and Transdisciplinary Research in Cancer of the Lung data consisting of 29,266 cases and 56,450 controls to analyze associations between candidate SNPs and lung cancer risk. Results: Multiple instrumental variable analysis incorporating six SNPs showed a 62% increased risk of overall non–small cell lung cancer [NSCLC; OR, 1.62; 95% confidence interval (CI), 1.15–2.27; P ¼ 0.005] and a 200% increased risk for small-cell lung cancer (OR, 3.00; 95% CI, 1.27–7.06; P ¼ 0.01). Results showed only a trending association with NSCLC histologic subtypes, which may be due to insufficient sample size and/or weak effect size. A series of sensitivity analysis retained these findings. Conclusions: Our findings suggest a causal relationship between elevated platelet count and increased risk of lung cancer and provide evidence of possible antiplatelet interventions for lung cancer prevention. Impact: These findings provide a better understanding of lung cancer etiology and potential evidence for antiplatelet interventions for lung cancer prevention.

Original languageEnglish
JournalCancer Epidemiology Biomarkers and Prevention
Volume28
Issue number5
Pages (from-to)935-942
Number of pages8
ISSN1055-9965
DOIs
Publication statusPublished - 2019

ID: 230250133