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



Zhu, Ying, Wei, Yongyue, Zhang, Ruyang, Dong, Xuesi, Shen, Sipeng, Zhao, Yang, Bai, Jianling, Albanes, Demetrius, Caporaso, Neil E, Landi, Maria Teresa
et al (show 67 more authors) (2019) Elevated Platelet Count Appears to Be Causally Associated with Increased Risk of Lung Cancer: A Mendelian Randomization Analysis. CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 28 (5). pp. 935-942.

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Abstract

<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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; <i>P</i> = 0.005] and a 200% increased risk for small-cell lung cancer (OR, 3.00; 95% CI, 1.27-7.06; <i>P</i> = 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.<h4>Conclusions</h4>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.<h4>Impact</h4>These findings provide a better understanding of lung cancer etiology and potential evidence for antiplatelet interventions for lung cancer prevention.

Item Type: Article
Uncontrolled Keywords: Blood Platelets, Humans, Carcinoma, Non-Small-Cell Lung, Carcinoma, Squamous Cell, Lung Neoplasms, Genetic Predisposition to Disease, Platelet Count, Prognosis, Risk Factors, Case-Control Studies, Polymorphism, Single Nucleotide, Small Cell Lung Carcinoma, Mendelian Randomization Analysis, Biomarkers, Tumor, Adenocarcinoma of Lung
Depositing User: Symplectic Admin
Date Deposited: 19 Feb 2019 16:18
Last Modified: 19 Jan 2023 01:02
DOI: 10.1158/1055-9965.EPI-18-0356
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3033115