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

Autor: Bouras E; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece., 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., 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., 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., Haycock PC; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK., Gunter MJ; Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France., Johansson M; Genomics Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France., Brennan P; Genomics Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France., Key T; Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK., Lewis SJ; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.; Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK., 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., Murphy N; Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France., Platz EA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Travis R; Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK., Yarmolinsky J; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK., Zuber V; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus, London, W2 1PG, UK., Martin P; School of Biochemistry, University of Bristol, Bristol, UK., Katsoulis M; Institute of Health Informatics, University College London, London, UK.; Health Data Research UK, London, UK., Freisling H; Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France., 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., Schulze MB; Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nutehtal, Germany.; Institute of Nutritional Science, University of Potsdam, Potsdam, Germany., Dossus L; Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France., 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., Amos CI; Baylor College of Medicine, Texas, USA., 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., Palaniswamy S; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus, London, W2 1PG, UK., Männikkö M; Northern Finland Birth Cohorts, Infrastructure for Population Studies, Faculty of Medicine, University of Oulu, Oulu, Finland., Auvinen J; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland., Herzig KH; Research Unit of Biomedicine, Medical Research Center, Faculty of Medicine, University of Oulu, and Oulu University Hospital, Oulu, Finland., Keinänen-Kiukaanniemi S; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland., Lehtimäki T; Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland., Salomaa V; Finnish Institute for Health and Welfare, Helsinki, Finland., 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., Salmi M; MediCity Research Laboratory, University of Turku, Turku, Finland.; Institute of Biomedicine, University of Turku, Turku, Finland., Jalkanen S; MediCity Research Laboratory, University of Turku, Turku, Finland.; Institute of Biomedicine, University of Turku, Turku, Finland., 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., 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., 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.
Jazyk: angličtina
Zdroj: BMC medicine [BMC Med] 2022 Jan 11; Vol. 20 (1), pp. 3. Date of Electronic Publication: 2022 Jan 11.
DOI: 10.1186/s12916-021-02193-0
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
Externí odkaz: