1. Elevated Platelet Count Appears to Be Causally Associated with Increased Risk of Lung Cancer: A Mendelian Randomization Analysis.
- Author
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Zhu Y, Wei Y, Zhang R, Dong X, Shen S, Zhao Y, Bai J, Albanes D, Caporaso NE, Landi MT, Zhu B, Chanock SJ, Gu F, Lam S, Tsao MS, Shepherd FA, Tardon A, Fernández-Somoano A, Fernandez-Tardon G, Chen C, Barnett MJ, Doherty J, Bojesen SE, Johansson M, Brennan P, McKay JD, Carreras-Torres R, Muley T, Risch A, Wichmann HE, Bickeboeller H, Rosenberger A, Rennert G, Saliba W, Arnold SM, Field JK, Davies MPA, Marcus MW, Wu X, Ye Y, Le Marchand L, Wilkens LR, Melander O, Manjer J, Brunnström H, Hung RJ, Liu G, Brhane Y, Kachuri L, Andrew AS, Duell EJ, Kiemeney LA, van der Heijden EH, Haugen A, Zienolddiny S, Skaug V, Grankvist K, Johansson M, Woll PJ, Cox A, Taylor F, Teare DM, Lazarus P, Schabath MB, Aldrich MC, Houlston RS, McLaughlin J, Stevens VL, Shen H, Hu Z, Dai J, Amos CI, Han Y, Zhu D, Goodman GE, Chen F, and Christiani DC
- Subjects
- Adenocarcinoma of Lung genetics, Adenocarcinoma of Lung pathology, Biomarkers, Tumor blood, Biomarkers, Tumor genetics, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell pathology, Case-Control Studies, Genetic Predisposition to Disease, Humans, Lung Neoplasms genetics, Lung Neoplasms pathology, Mendelian Randomization Analysis, Platelet Count, Polymorphism, Single Nucleotide, Prognosis, Risk Factors, Small Cell Lung Carcinoma genetics, Small Cell Lung Carcinoma pathology, Adenocarcinoma of Lung blood, Blood Platelets pathology, Carcinoma, Non-Small-Cell Lung blood, Carcinoma, Squamous Cell blood, Lung Neoplasms blood, Small Cell Lung Carcinoma blood
- 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 = 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.)
- Published
- 2019
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