Circulating inflammatory cytokines and risk of five cancers: a Mendelian randomization analysis.

Cytokines / genetics Female Genome-Wide Association Study Humans Male Mendelian Randomization Analysis Meta-Analysis as Topic Ovarian Neoplasms / epidemiology Polymorphism, Single Nucleotide Risk Factors
Cancer Cytokines Inflammation Mendelian randomisation

Journal

BMC medicine
ISSN: 1741-7015
Titre abrégé: BMC Med
Pays: England
ID NLM: 101190723

Informations de publication

Date de publication:
11 01 2022
Historique:
received: 19 07 2021
accepted: 18 11 2021
entrez: 11 1 2022
pubmed: 12 1 2022
medline: 27 1 2022
Statut: epublish

Résumé

Epidemiological and experimental evidence has linked chronic inflammation to cancer aetiology. It is unclear whether associations for specific inflammatory biomarkers are causal or due to bias. In order to examine whether altered genetically predicted concentration of circulating cytokines are associated with cancer development, we performed a two-sample Mendelian randomisation (MR) analysis. Up to 31,112 individuals of European descent were included in genome-wide association study (GWAS) meta-analyses of 47 circulating cytokines. Single nucleotide polymorphisms (SNPs) robustly associated with the cytokines, located in or close to their coding gene (cis), were used as instrumental variables. Inverse-variance weighted MR was used as the primary analysis, and the MR assumptions were evaluated in sensitivity and colocalization analyses and a false discovery rate (FDR) correction for multiple comparisons was applied. Corresponding germline GWAS summary data for five cancer outcomes (breast, endometrial, lung, ovarian, and prostate), and their subtypes were selected from the largest cancer-specific GWASs available (cases ranging from 12,906 for endometrial to 133,384 for breast cancer). There was evidence of inverse associations of macrophage migration inhibitory factor with breast cancer (OR per SD = 0.88, 95% CI 0.83 to 0.94), interleukin-1 receptor antagonist with endometrial cancer (0.86, 0.80 to 0.93), interleukin-18 with lung cancer (0.87, 0.81 to 0.93), and beta-chemokine-RANTES with ovarian cancer (0.70, 0.57 to 0.85) and positive associations of monokine induced by gamma interferon with endometrial cancer (3.73, 1.86 to 7.47) and cutaneous T-cell attracting chemokine with lung cancer (1.51, 1.22 to 1.87). These associations were similar in sensitivity analyses and supported in colocalization analyses. Our study adds to current knowledge on the role of specific inflammatory biomarker pathways in cancer aetiology. Further validation is needed to assess the potential of these cytokines as pharmacological or lifestyle targets for cancer prevention.

Sections du résumé

BACKGROUND
Epidemiological and experimental evidence has linked chronic inflammation to cancer aetiology. It is unclear whether associations for specific inflammatory biomarkers are causal or due to bias. In order to examine whether altered genetically predicted concentration of circulating cytokines are associated with cancer development, we performed a two-sample Mendelian randomisation (MR) analysis.
METHODS
Up to 31,112 individuals of European descent were included in genome-wide association study (GWAS) meta-analyses of 47 circulating cytokines. Single nucleotide polymorphisms (SNPs) robustly associated with the cytokines, located in or close to their coding gene (cis), were used as instrumental variables. Inverse-variance weighted MR was used as the primary analysis, and the MR assumptions were evaluated in sensitivity and colocalization analyses and a false discovery rate (FDR) correction for multiple comparisons was applied. Corresponding germline GWAS summary data for five cancer outcomes (breast, endometrial, lung, ovarian, and prostate), and their subtypes were selected from the largest cancer-specific GWASs available (cases ranging from 12,906 for endometrial to 133,384 for breast cancer).
RESULTS
There was evidence of inverse associations of macrophage migration inhibitory factor with breast cancer (OR per SD = 0.88, 95% CI 0.83 to 0.94), interleukin-1 receptor antagonist with endometrial cancer (0.86, 0.80 to 0.93), interleukin-18 with lung cancer (0.87, 0.81 to 0.93), and beta-chemokine-RANTES with ovarian cancer (0.70, 0.57 to 0.85) and positive associations of monokine induced by gamma interferon with endometrial cancer (3.73, 1.86 to 7.47) and cutaneous T-cell attracting chemokine with lung cancer (1.51, 1.22 to 1.87). These associations were similar in sensitivity analyses and supported in colocalization analyses.
CONCLUSIONS
Our study adds to current knowledge on the role of specific inflammatory biomarker pathways in cancer aetiology. Further validation is needed to assess the potential of these cytokines as pharmacological or lifestyle targets for cancer prevention.

Identifiants

DOI: 10.1186/s12916-021-02193-0 PMID: 35012533 PMC: PMC8750876
pubmed: 35012533
doi: 10.1186/s12916-021-02193-0
pii: 10.1186/s12916-021-02193-0
pmc: PMC8750876
doi:

Substances chimiques

Cytokines 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3

Subventions

Organisme : British Heart Foundation
ID : FS/18/5/33319
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : UG1 CA189974
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA182883
Pays : United States
Organisme : Cancer Research UK
ID : C18281/A29019
Pays : United Kingdom

Investigateurs

None Cruk
None Caps
None Pegasus

Informations de copyright

© 2021. The Author(s).

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Auteurs

Emmanouil Bouras (E)

Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.

Ville Karhunen (V)

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus, London, W2 1PG, UK.
Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
Research Unit of Mathematical Sciences, University of Oulu, Oulu, Finland.

Dipender Gill (D)

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus, London, W2 1PG, UK.
Novo Nordisk Research Centre Oxford, Old Road Campus, Oxford, UK.
Clinical Pharmacology Group, Pharmacy and Medicines Directorate, St George's University Hospitals NHS Foundation Trust, London, UK.
Clinical Pharmacology and Therapeutics Section, Institute for Infection and Immunity, St George's, University of London, London, UK.

Jian Huang (J)

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus, London, W2 1PG, UK.
Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.

Philip C Haycock (PC)

MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.

Marc J Gunter (MJ)

Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.

Mattias Johansson (M)

Genomics Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.

Paul Brennan (P)

Genomics Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.

Tim Key (T)

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Sarah J Lewis (SJ)

MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.

Richard M Martin (RM)

MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK.

Neil Murphy (N)

Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.

Elizabeth A Platz (EA)

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Ruth Travis (R)

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

James Yarmolinsky (J)

MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.

Verena Zuber (V)

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus, London, W2 1PG, UK.

Paul Martin (P)

School of Biochemistry, University of Bristol, Bristol, UK.

Michail Katsoulis (M)

Institute of Health Informatics, University College London, London, UK.
Health Data Research UK, London, UK.

Heinz Freisling (H)

Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.

Therese Haugdahl Nøst (TH)

Department of Community Medicine, Faculty of Health Sciences, Arctic University of Norway, Tromsø, Norway.
K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.

Matthias B Schulze (MB)

Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nutehtal, Germany.
Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.

Laure Dossus (L)

Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.

Rayjean J Hung (RJ)

Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute of Sinai Health System, Toronto, Canada.
Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.

Christopher I Amos (CI)

Baylor College of Medicine, Texas, USA.

Ari Ahola-Olli (A)

The Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.

Saranya Palaniswamy (S)

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus, London, W2 1PG, UK.

Minna Männikkö (M)

Northern Finland Birth Cohorts, Infrastructure for Population Studies, Faculty of Medicine, University of Oulu, Oulu, Finland.

Juha Auvinen (J)

Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.

Karl-Heinz Herzig (KH)

Research Unit of Biomedicine, Medical Research Center, Faculty of Medicine, University of Oulu, and Oulu University Hospital, Oulu, Finland.

Sirkka Keinänen-Kiukaanniemi (S)

Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.

Terho Lehtimäki (T)

Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

Veikko Salomaa (V)

Finnish Institute for Health and Welfare, Helsinki, Finland.

Olli Raitakari (O)

Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.

Marko Salmi (M)

MediCity Research Laboratory, University of Turku, Turku, Finland.
Institute of Biomedicine, University of Turku, Turku, Finland.

Sirpa Jalkanen (S)

MediCity Research Laboratory, University of Turku, Turku, Finland.
Institute of Biomedicine, University of Turku, Turku, Finland.

Marjo-Riitta Jarvelin (MR)

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus, London, W2 1PG, UK.
Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
Unit of Primary Care, Oulu University Hospital, Oulu, Finland.

Abbas Dehghan (A)

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus, London, W2 1PG, UK.
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
UK Dementia Research Institute at Imperial College London, London, UK.

Konstantinos K Tsilidis (KK)

Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. k.tsilidis@imperial.ac.uk.
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus, London, W2 1PG, UK. k.tsilidis@imperial.ac.uk.

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Classifications MeSH

questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Circulating inflammatory cytokines and risk of...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Circulating inflammatory cytokines and risk of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Circulating inflammatory cytokines and risk of...
questionsmedicales.fr › Techniques d'investigation › Analyse de randomisation mendélienne › Circulating inflammatory cytokines and risk of...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Méthodologie en recherche épidémiologique › Méta-analyse comme sujet › Circulating inflammatory cytokines and risk of...
questionsmedicales.fr › Maladies endocriniennes › Troubles gonadiques › Maladies ovariennes › Tumeurs de l'ovaire › Circulating inflammatory cytokines and risk of...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Circulating inflammatory cytokines and risk of...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Risque › Facteurs de risque › Circulating inflammatory cytokines and risk of...