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

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(MR) analysis by an inverse-weighted (IVW) method, in addition to a series of sensitivity analyses. Summary data for associations between single nucleotide polymorphisms (SNPs) and platelet count is from a recent publication including 48,666 Caucasian Europeans and International Lung Cancer Consortium and Transdisciplinary Research in Cancer of the Lung data consisting of 29,266 cases and 56,450 controls analyze associations between candidate single nucleotide polymorphisms and lung cancer risk. RESULTS: Multiple instrumental variable analysis incorporating six SNPs showed a 62% increased risk of overall NSCLC (OR, 1.62; 95%CI, 1.15-2.27; P = 0.005) and 200% increased risk for small cell lung cancer (OR, 3.00; 95%CI, 1.27-7.06; P = 0.01), respectively. Results showed only a trending association with NSCLC histological 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 anti-platelet interventions for lung cancer prevention. IMPACT: Our findings suggest a causal relationship of increased platelet count and risk of lung cancer, which also provide a better understanding of lung cancer etiology and potential evidence for anti-platelet interventions for lung cancer prevention.