Effects of tumour necrosis factor on cardiovascular disease and cancer: A two-sample Mendelian randomization study.

Cardiovascular Diseases / diagnosis Disease Susceptibility Female Genetic Association Studies Genetic Predisposition to Disease Humans Male Mendelian Randomization Analysis Meta-Analysis as Topic Neoplasms / diagnosis Odds Ratio Polymorphism, Single Nucleotide Tumor Necrosis Factors / genetics
Cancer Cardiovascular disease Tumour necrosis factor

Journal

EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039

Informations de publication

Date de publication:
Sep 2020
Historique:
received: 30 05 2020
revised: 26 07 2020
accepted: 03 08 2020
pubmed: 18 8 2020
medline: 29 6 2021
entrez: 18 8 2020
Statut: ppublish

Résumé

Tumour necrosis factor (TNF) inhibitors are used in the treatment of certain autoimmune diseases but given the role of TNF in tumour biology and atherosclerosis, such therapies may influence the risk of cancer and cardiovascular disease. We conducted a Mendelian randomization study to explore whether TNF levels are causally related to cardiovascular disease and cancer. Single-nucleotide polymorphisms associated with TNF levels at genome-wide significance were identified from a genome-wide association study of 30 912 European-ancestry individuals. Three TNF-associated single-nucleotide polymorphisms associated with higher risk of autoimmune diseases were used as instrumental variables. Summary-level data for 14 cardiovascular diseases, overall cancer and 14 site-specific cancers were obtained from UK Biobank and consortia. Genetically-predicted TNF levels were positively associated with coronary artery disease (odds ratio (OR) 2.25; 95% confidence interval (CI) 1.50, 3.37) and ischaemic stroke (OR 2.27; 95% CI 1.50, 3.43), and inversely associated with overall cancer (OR 0.54; 95% CI 0.42, 0.69), breast cancer (OR 0.51; 95% CI 0.39, 0.67), and colorectal cancer (OR 0.20; 95% CI 0.09, 0.45). There were suggestive associations of TNF with venous thromboembolism (OR 2.18; 95% CI 1.32, 3.59), endometrial cancer (OR 0.25; 95% CI 0.07, 0.94), and lung cancer (OR 0.45; 95% CI 0.21, 0.94). This study found evidence of causal associations of increased TNF levels with higher risk of common cardiovascular diseases and lower risk of overall and certain cancers.

Sections du résumé

BACKGROUND BACKGROUND
Tumour necrosis factor (TNF) inhibitors are used in the treatment of certain autoimmune diseases but given the role of TNF in tumour biology and atherosclerosis, such therapies may influence the risk of cancer and cardiovascular disease. We conducted a Mendelian randomization study to explore whether TNF levels are causally related to cardiovascular disease and cancer.
METHODS METHODS
Single-nucleotide polymorphisms associated with TNF levels at genome-wide significance were identified from a genome-wide association study of 30 912 European-ancestry individuals. Three TNF-associated single-nucleotide polymorphisms associated with higher risk of autoimmune diseases were used as instrumental variables. Summary-level data for 14 cardiovascular diseases, overall cancer and 14 site-specific cancers were obtained from UK Biobank and consortia.
FINDINGS RESULTS
Genetically-predicted TNF levels were positively associated with coronary artery disease (odds ratio (OR) 2.25; 95% confidence interval (CI) 1.50, 3.37) and ischaemic stroke (OR 2.27; 95% CI 1.50, 3.43), and inversely associated with overall cancer (OR 0.54; 95% CI 0.42, 0.69), breast cancer (OR 0.51; 95% CI 0.39, 0.67), and colorectal cancer (OR 0.20; 95% CI 0.09, 0.45). There were suggestive associations of TNF with venous thromboembolism (OR 2.18; 95% CI 1.32, 3.59), endometrial cancer (OR 0.25; 95% CI 0.07, 0.94), and lung cancer (OR 0.45; 95% CI 0.21, 0.94).
INTERPRETATION CONCLUSIONS
This study found evidence of causal associations of increased TNF levels with higher risk of common cardiovascular diseases and lower risk of overall and certain cancers.

Identifiants

DOI: 10.1016/j.ebiom.2020.102956 PMID: 32805626 PMC: PMC7452586
pubmed: 32805626
pii: S2352-3964(20)30332-7
doi: 10.1016/j.ebiom.2020.102956
pmc: PMC7452586
pii:
doi:

Substances chimiques

Tumor Necrosis Factors 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

102956

Subventions

Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00002/7
Pays : United Kingdom

Informations de copyright

Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interests SCL reports grants from Swedish Research Council (Vetenskapsrådet; grant no. 2019-00977), grants from Swedish Research Council for Health, Working Life and Welfare (Forte; grant no. 2018-00123), grants from Swedish Heart-Lung Foundation (Hjärt-Lungfonden; grant no. 20190247), during the conduct of the study. AMM reports grants from EC-Innovative Medicines Initiative (BigData@Heart), during the conduct of the study; .All other authors declare no conflicts of interest.

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Auteurs

Shuai Yuan (S)

Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm 17177, Sweden; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

Paul Carter (P)

Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.

Maria Bruzelius (M)

Coagulation Unit, Department of Hematology, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Mathew Vithayathil (M)

MRC Cancer Unit, University of Cambridge, Cambridge, United Kingdom.

Siddhartha Kar (S)

MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, United Kingdom.

Amy M Mason (AM)

British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge and Cambridge University Hospitals, Cambridge, United Kingdom.

Ang Lin (A)

Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.

Stephen Burgess (S)

Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; MRC Biostatistics Unit, University of Cambridge, Cambridge, United Kingdom.

Susanna C Larsson (SC)

Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm 17177, Sweden; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. Electronic address: susanna.larsson@ki.se.

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questionsmedicales.fr › Maladies cardiovasculaires › Effects of tumour necrosis factor on...
questionsmedicales.fr › Phénomènes physiologiques › Constitution physique › Prédisposition aux maladies › Effects of tumour necrosis factor on...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Études d'associations génétiques › Effects of tumour necrosis factor on...
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questionsmedicales.fr › Techniques d'investigation › Analyse de randomisation mendélienne › Effects of tumour necrosis factor on...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Méthodologie en recherche épidémiologique › Méta-analyse comme sujet › Effects of tumour necrosis factor on...
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