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Olle Melander

Principal investigator

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Elevated Platelet Count Appears to Be Causally Associated with Increased Risk of Lung Cancer: A Mendelian Randomization Analysis

Author

  • Ying Zhu
  • Olle Melander
  • Jonas Manjer
  • Hans Brunnström
  • David C. Christiani

Summary, in English

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 = 0.005] and a 200% increased risk for small-cell lung cancer (OR, 3.00; 95% CI, 1.27-7.06; P = 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. ©2019 American Association for Cancer Research.

Department/s

  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health
  • Cardiovascular Research - Hypertension
  • Surgery
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
  • Improved diagnostics and prognostics of lung cancer and metastases to the lungs
  • Tumor microenvironment

Publishing year

2019

Language

English

Pages

935-942

Publication/Series

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

Volume

28

Issue

5

Document type

Journal article

Publisher

American Association for Cancer Research

Topic

  • Medical Genetics
  • Cancer and Oncology

Status

Published

Research group

  • Cardiovascular Research - Hypertension
  • Surgery
  • Improved diagnostics and prognostics of lung cancer and metastases to the lungs

ISBN/ISSN/Other

  • ISSN: 1538-7755