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

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 ChenMatthew 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

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

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
Pages (from-to)935-942
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume28
Issue number5
DOIs
StatePublished - May 2019

Bibliographical note

Funding Information:
We thank the participants and staff for their important contributions to this study. This study was supported by the NIH (CA092824 and CA209414, to D.C. Christiani), National Natural Science Foundation of China (81530088 and 81473070, to F. Chen; 81373102, to Y. Zhao), State's Key Project of Research and Development Program (2016YFE0204900, to F. Chen), Key Project of Natural Science Foundation of Jiangsu, China (14JA31002, to F. Chen), A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and Outstanding Young Teachers Training Program of Nanjing Medical University (to Y.Y. Wei). Transdisciplinary Research for Cancer in Lung (TRICL) and Oncoarray funding sources are detailed as follows: Transdisciplinary Research for Cancer in Lung (TRICL) of the International Lung Cancer Consortium (ILCCO) was supported by grants U19-CA148127 and CA148127S1. ILCCO data harmonization was supported by the Cancer Care Ontario Research Chair of Population Studies (to R.J. Hung) and the Lunenfeld-Tanenbaum Research Institute, Sinai Health System. The CAPUA study was supported by FIS-FEDER/Spain grants FIS-01/310, FIS-PI03-0365, and FIS-07-BI060604; FICYT/Asturias grants FICYT PB02-67 and FICYT IB09-133; and the University Institute of Oncology (IUOPA) of the University of Oviedo and the Ciber de Epidemiologiay Salud Pública (CIBERESP), Spain. Work performed in the CARET study was supported by the NIH/NCI UM1 CA167462 (principal investigator: G.E. Goodman), NIH UO1-CA6367307 (principalinvestigators:Omen,G.E.Goodman), NIHR01CA111703(principal investigator: C. Chen), and NIH 5R01 CA151989-01A1 (principal investigator: J. Doherty). The Liverpool Lung project was supported by the Roy Castle Lung Cancer Foundation. The Harvard Lung Cancer Study was supported by the NIH/ NCI grants CA092824, CA090578, and CA074386. The Multiethnic Cohort Study was partially supported by NIH grants CA164973, CA033619, CA63464, and CA148127. Work performed in the MSH–PMH study was supported by the Canadian Cancer Society Research Institute (020214), Ontario Institute of Cancer and Cancer Care Ontario Chair Award (to R.J. Hung and G. Liu), and Alan Brown Chair and Lusi Wong Programs at Princess Margaret Hospital Foundation. NJLCS was funded by the State Key Program of National Natural Science of China (81230067), National Key Basic Research Program (2011CB503805), and Major Program of the National Natural Science Foundation of China (81390543). The Norway study was supported by the Norwegian Cancer Society, Norwegian Research Council. The Shanghai Cohort Study (SCS) was supported by NIH R01 CA144034 (principal investigator: J.M. Yuan) and UM1 CA182876 (principal investigator: J.M. Yuan). The Singapore Chinese Health Study (SCHS) was supported by NIH R01 CA144034 (principal investigator: J.M. Yuan) and UM1 CA182876 (principal investigator: J.M. Yuan). Work in the TLC study has been supported in part by the James & Esther

Publisher Copyright:
© 2019 American Association for Cancer Research.

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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