期刊
EBIOMEDICINE
卷 59, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ebiom.2020.102956
关键词
Cancer; Cardiovascular disease; Tumour necrosis factor
资金
- Swedish Research Council (Vetenskapsradet) [2019-00977]
- Swedish Research Council for Health, Working Life and Welfare (Forte) [2018-00123]
- Swedish Heart-Lung Foundation (Hjart-Lungfonden) [20190247]
- Stockholm county council
- Cancer Research UK programme grant, the Integrative Cancer Epidemiology Programme [C18281/A19169]
- EC-Innovative Medicines Initiative (BigData@Heart)
- Sir Henry Dale Fellowship - Wellcome Trust [204623/Z/16/Z]
- Royal Society [204623/Z/16/Z]
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: 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: 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: 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. (C) 2020 The Author(s). Published by Elsevier B.V.
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