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

Shuai Yuan; Paul Carter; Maria Bruzelius; Mathew Vithayathil; Siddhartha Kar; Amy M Mason; Ang Lin; Stephen  Burgess; Susanna C Larsson

doi:10.1016/j.ebiom.2020.102956

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

Shuai Yuan
, Paul Carter
, Maria Bruzelius
, Mathew Vithayathil
, Siddhartha Kar
, Amy M Mason
, Ang Lin
, Stephen Burgess
, Susanna C Larsson

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

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.

Original language	English
Article number	102956
Number of pages	8
Journal	eBioMedicine
Volume	59
DOIs	https://doi.org/10.1016/j.ebiom.2020.102956
Publication status	Published - 15 Aug 2020

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

cancer
cardiovascular disease
tumour necrosis factor

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@article{f7bd03b0fcb04d4ba785dec166f47531,

title = "Effects of tumour necrosis factor on cardiovascular disease and cancer: A two-sample Mendelian randomization study",

abstract = "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.",

keywords = "cancer, cardiovascular disease, tumour necrosis factor",

author = "Shuai Yuan and Paul Carter and Maria Bruzelius and Mathew Vithayathil and Siddhartha Kar and Mason, \{Amy M\} and Ang Lin and Stephen Burgess and Larsson, \{Susanna C\}",

year = "2020",

month = aug,

day = "15",

doi = "10.1016/j.ebiom.2020.102956",

language = "English",

volume = "59",

journal = "eBioMedicine",

issn = "2352-3964",

publisher = "Elsevier B.V.",

}

TY - JOUR

T1 - Effects of tumour necrosis factor on cardiovascular disease and cancer

T2 - A two-sample Mendelian randomization study

AU - Yuan, Shuai

AU - Carter, Paul

AU - Bruzelius, Maria

AU - Vithayathil, Mathew

AU - Kar, Siddhartha

AU - Mason, Amy M

AU - Lin, Ang

AU - Burgess, Stephen

AU - Larsson, Susanna C

PY - 2020/8/15

Y1 - 2020/8/15

N2 - 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.

AB - 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.

KW - cancer

KW - cardiovascular disease

KW - tumour necrosis factor

U2 - 10.1016/j.ebiom.2020.102956

DO - 10.1016/j.ebiom.2020.102956

M3 - Article (Academic Journal)

C2 - 32805626

SN - 2352-3964

VL - 59

JO - eBioMedicine

JF - eBioMedicine

M1 - 102956

ER -

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

Abstract

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Keywords

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