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Cancer Epidemiol Biomarkers Prev. 2019 May;28(5):935-942. doi: 10.1158/1055-9965.EPI-18-0356. Epub 2019 Jan 30.

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

Author information

1
Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
2
Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts.
3
China International Cooperation Center (CICC) for Environment and Human Health, Nanjing Medical University, Nanjing, China.
4
Department of Epidemiology and Biostatistics, School of Public Health, Southeast University, Nanjing, China.
5
Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
6
Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, New York.
7
British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
8
University Health Network, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
9
University of Oviedo and CIBERESP, Faculty of Medicine, Oviedo, Spain.
10
Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, Washington.
11
Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
12
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
13
Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen, Denmark.
14
International Agency for Research on Cancer, World Health Organization, Lyon, France.
15
Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany.
16
Translational Lung Research Center Heidelberg (TLRC-H), Heidelberg, Germany.
17
German Center for Lung Research (DZL), Heidelberg, Germany.
18
University of Salzburg and Cancer Cluster Salzburg, Salzburg, Austria.
19
Research Unit of Molecular Epidemiology, Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
20
Department of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen, Germany.
21
Department of Community Medicine and Epidemiology, Clalit National Cancer Control Center at Carmel Medical Center and Technion Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
22
Markey Cancer Center, University of Kentucky, Lexington, Kentucky.
23
Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
24
Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas.
25
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
26
Faculty of Medicine, Lund University, Lund, Sweden.
27
Department of Pathology, Lund University, Lund, Sweden.
28
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, University of Toronto, Toronto, Ontario, Canada.
29
Department of Epidemiology, Geisel School of Medicine, Hanover, New Hampshire.
30
Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
31
Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands.
32
National Institute of Occupational Health, Oslo, Norway.
33
Department of Medical Biosciences, Umeå University, Umeå, Sweden.
34
Department of Oncology and Metabolism, University of Sheffield, Sheffield, United Kingdom.
35
School of Health and Related Research, University of Sheffield, England, United Kingdom.
36
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, Washington.
37
Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
38
Department of Thoracic Surgery, Division of Epidemiology, Vanderbilt University Medical Center, Nashville, Tennessee.
39
The Institute of Cancer Research, London, England.
40
Public Health Ontario, Toronto, Ontario, Canada.
41
American Cancer Society, Inc., Atlanta, Georgia.
42
Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.
43
Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
44
Swedish Medical Group, Seattle, Washington.
45
Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China. fengchen@njmu.edu.cn dchris@hsph.harvard.edu.
#
Contributed equally

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.

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