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dc.contributor.authorBouras, Emmanouil
dc.contributor.authorKarhunen, Ville
dc.contributor.authorGill, Dipender
dc.contributor.authorHuang, Jian
dc.contributor.authorHaycock, Philip C.
dc.contributor.authorGunter, Marc J.
dc.contributor.authorJohansson, Mattias
dc.contributor.authorBrennan, Paul
dc.contributor.authorKey, Tim
dc.contributor.authorLewis, Sarah J.
dc.contributor.authorMartin, Richard M.
dc.contributor.authorMurphy, Neil
dc.contributor.authorPlatz, Elizabeth A.
dc.contributor.authorTravis, Ruth
dc.contributor.authorYarmolinsky, James
dc.contributor.authorZuber, Verena
dc.contributor.authorMartin, Paul
dc.contributor.authorKatsoulis, Michail
dc.contributor.authorFreisling, Heinz
dc.contributor.authorNøst, Therese Haugdahl
dc.contributor.authorSchulze, Matthias B.
dc.contributor.authorDossus, Laure
dc.contributor.authorHung, Rayjean J.
dc.contributor.authorAmos, Christopher I.
dc.contributor.authorAhola-Olli, Ari
dc.contributor.authorPalaniswamy, Saranya
dc.contributor.authorMännikkö, Minna
dc.contributor.authorAuvinen, Juha
dc.contributor.authorHerzig, Karl-Heinz
dc.contributor.authorKeinänen-Kiukaanniemi, Sirkka
dc.contributor.authorLehtimäki, Terho
dc.contributor.authorSalomaa, Veikko
dc.contributor.authorRaitakari, Olli
dc.contributor.authorSalmi, Marko
dc.contributor.authorJalkanen, Sirpa
dc.contributor.authorJarvelin, Marjo-Riitta
dc.contributor.authorDehghan, Abbas
dc.contributor.authorTsilidis, Konstantinos K.
dc.date.accessioned2022-08-25T11:55:37Z
dc.date.available2022-08-25T11:55:37Z
dc.date.issued2022-01-11
dc.description.abstractBackground - 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.<p> <p>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).<p> <p>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.<p> <p>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.en_US
dc.identifier.citationBouras, Karhunen, Gill, Huang, Haycock, Gunter, Johansson, Brennan, Key, Lewis, Martin, Murphy, Platz, Travis, Yarmolinsky, Zuber, Martin, Katsoulis, Freisling, Nøst, Schulze, Dossus, Hung, Amos, Ahola-Olli, Palaniswamy, Männikkö, Auvinen, Herzig, Keinänen-Kiukaanniemi, Lehtimäki, Salomaa, Raitakari, Salmi, Jalkanen, Jarvelin, Dehghan, Tsilidis. Circulating inflammatory cytokines and risk of five cancers: a Mendelian randomization analysis. BMC Medicine. 2022;20(1)en_US
dc.identifier.cristinIDFRIDAID 2020546
dc.identifier.doi10.1186/s12916-021-02193-0
dc.identifier.issn1741-7015
dc.identifier.urihttps://hdl.handle.net/10037/26423
dc.language.isoengen_US
dc.publisherBMCen_US
dc.relation.journalBMC Medicine
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/EXCELLENT SCIENCE/721567/Norway/Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe/CAPICE/en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/SOCIETAL CHALLENGES /848158/Norway/Causative mechanisms & integrative models linking early-life-stress to psycho-cardio-metabolic multi-morbidity/EarlyCause/en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/SOCIETAL CHALLENGES/666881/Norway/Small vessel diseases in a mechanistic perspective: Targets for Intervention Affected pathways and mechanistic exploitation for prevention of stroke and dementia/SVDs-at-target/en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/SOCIETAL CHALLENGES/667375/Norway/Common mechanisms and pathways in Stroke and Alzheimer's disease/CoSTREAM/en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7-HEALTH/601456/Norway/Exploitation of genomic variants affecting coronary artery disease and stroke risk for therapeutic intervention/CVGENES-AT-TARGET/en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/SOCIETAL CHALLENGES/825762/Norway/Metabolic effects of Endocrine Disrupting Chemicals: novel testing METhods and adverse outcome pathways/EDCMET/en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2022 The Author(s)en_US
dc.titleCirculating inflammatory cytokines and risk of five cancers: a Mendelian randomization analysisen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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