Journal
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
Volume 28, Issue 5, Pages 935-942Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1055-9965.EPI-18-0356
Keywords
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Funding
- NIH [CA092824, CA209414, UO1-CA6367307, R01CA111703, 5R01 CA151989-01A1, CA164973, CA033619, CA63464, CA148127, R01 CA144034, UM1 CA182876, P50 CA070907, R01 CA176568, CA194393]
- National Natural Science Foundation of China [81530088, 81473070, 81373102]
- State's Key Project of Research and Development Program [2016YFE0204900]
- Key Project of Natural Science Foundation of Jiangsu, China [14JA31002]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Outstanding Young Teachers Training Program of Nanjing Medical University
- Cancer Care Ontario Research Chair of Population Studies
- Lunenfeld-Tanenbaum Research Institute
- Sinai Health System
- FIS-FEDER/Spain [FIS-01/310, FIS-PI03-0365, FIS-07-BI060604]
- FICYT/Asturias [FICYT PB02-67, FICYT IB09-133]
- University Institute of Oncology (IUOPA) of the University of Oviedo
- Ciber de Epidemiologiay Salud Publica (CIBERESP), Spain
- NIH/NCI [CA092824, UM1 CA167462, CA090578, CA074386, K07CA172294]
- Canadian Cancer Society Research Institute [020214]
- Ontario Institute of Cancer and Cancer Care Ontario Chair Award
- Alan Brown Chair and Lusi Wong Programs at Princess Margaret Hospital Foundation
- State Key Program of National Natural Science of China [81230067]
- National Key Basic Research Program [2011CB503805]
- Major Program of the National Natural Science Foundation of China [81390543]
- Norwegian Cancer Society, Norwegian Research Council
- James & Esther King Biomedical Research Program [09KN-15]
- NIH Specialized Programs of Research Excellence (SPORE) [P50 CA119997]
- Cancer Center Support Grant (CCSG) at the H. LeeMoffitt Cancer Center and Research Institute, an NCI designated Comprehensive Cancer Center [P30-CA76292]
- Vanderbilt Nature Genetics
- National Center for Advancing Translational Sciences (NCATS)/NIH [UL1TR000445]
- Chief Physician Johan Boserup and Lise Boserup Fund
- Danish Medical Research Council
- Herlev Hospital
- National Center for Research Resources (NCRR), a component of the NIH [P20RR018787]
- Department of Defense [10153006 (W81XWH-11-1-0781)]
- UK Center for Clinical and Translational Science, NIH [UL1TR000117]
- Markey Cancer Center NCI Cancer Center Support Grant [P30 CA177558]
- Shared Resource Facilities: Cancer Research Informatics, Biospecimen and Tissue Procurement, and Biostatistics and Bioinformatics
- Cancer Prevention & Research Institute of Texas [RP130502]
- University of Texas MD Anderson Cancer Center
- National Institutes on Drug Abuse (NIDA) [R01-DA017932]
- Nofer Institute of Occupational Medicine
- Sheffield Hospitals Charity
- Sheffield Experimental Cancer Medicine Centre
- Weston Park Hospital Cancer Charity
- Intramural Research Program of the Division of Cancer Epidemiology and Genetics, NCI
- Intramural Research Program of NIH, NCI, Division of Cancer Epidemiology and Genetics
- Roswell Park Cancer Institute and Cancer Center Supporting Grant [P30CA016056]
- NCI, NIH [P01 CA168530, U01 CA164973]
- Canadian Institutes for Health Research
- Intramural Research Program of the NIH NCI's Division of Cancer Epidemiology
- American Cancer Society
- Cancer Research UK [C1298/A8362, C1298/A8780, C18281/A19169]
- [U19-CA148127]
- [CA148127S1]
- [1S10RR025141-01]
- NATIONAL CANCER INSTITUTE [U01CA209414, P30CA177558, U01CA167462, P30CA076292, UM1CA167462, P01CA168530, U01CA164973, P50CA070907, K07CA172294, R01CA176568, U01CA194393, ZIACP010195, UM1CA182876, P30CA071789, P30CA016056] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR000445] Funding Source: NIH RePORTER
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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 nonsmall 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.
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