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

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Date
2019-05
ICR Author
Houlston, Richard
Author
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, M-S
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, H-E
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
Christiani, DC
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Type
Journal Article
Metadata
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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.
URI
https://repository.icr.ac.uk/handle/internal/3179
DOI
https://doi.org/10.1158/1055-9965.epi-18-0356
Collections
  • Genetics and Epidemiology
Subject
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
Research team
Cancer Genomics
Language
eng
Date accepted
2019-01-17
License start date
2019-05
Citation
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2019, 28 (5), pp. 935 - 942

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