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Circulating inflammatory and immune response proteins and endometrial cancer risk: a nested case-control study and Mendelian randomization analyses

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dc.contributor.authorWang, Sabrina E
dc.contributor.authorViallon, Vivian
dc.contributor.authorLee, Matthew
dc.contributor.authorDimou, Niki
dc.contributor.authorHamilton, Fergus
dc.contributor.authorBiessy, Carine
dc.contributor.authorO'Mara, Tracy
dc.contributor.authorKyrgiou, Maria
dc.contributor.authorCrosbie, Emma J
dc.contributor.authorTruong, Therese
dc.contributor.authorSeveri, Gianluca
dc.contributor.authorKaaks, Rudolf
dc.contributor.authorFortner, Renée Turzanski
dc.contributor.authorSchulze, Matthias B
dc.contributor.authorBendinelli, Benedetta
dc.contributor.authorSabina, Sieri
dc.contributor.authorTumino, Rosario
dc.contributor.authorSacerdote, Carlotta
dc.contributor.authorPanico, Salvatore
dc.contributor.authorCrous-Bou, Marta
dc.contributor.authorSanchez-Perez, Maria-Jose
dc.contributor.authorAizpurua, Amaia
dc.contributor.authorPalacios, Daniel Rodriguez
dc.contributor.authorGuevara, Marcela
dc.contributor.authorTravis, Ruth C
dc.contributor.authorTsilidis, Konstantinos K
dc.contributor.authorHeath, Alicia
dc.contributor.authorYarmolinsky, James
dc.contributor.authorRinaldi, Sabina
dc.contributor.authorGunter, Marc J
dc.contributor.authorDossus, Laure
dc.contributor.authoraffiliation[Sanchez-Perez,MJ] Escuela Andaluza de Salud Pública (EASP), Granada, Spain
dc.contributor.authoraffiliation[Sanchez-Perez,MJ] Instituto de Investigación Biosanitaria, Granada, Spain
dc.contributor.authoraffiliation[Sanchez-Perez,MJ] Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
dc.contributor.funderWorld Cancer Research Fund International
dc.contributor.funderInstitut National du Cancer (INCa).
dc.date.accessioned2024-10-31T11:33:27Z
dc.date.available2024-10-31T11:33:27Z
dc.date.issued2024-10
dc.description.abstractBackground: Inflammation and immune dysregulation are hypothesized contributors to endometrial carcinogenesis; however, the precise underlying mechanisms remain unclear. Methods: We measured pre-diagnostically 152 plasma protein biomarkers in 624 endometrial cancer case-control pairs nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Odds ratios (ORs) were estimated using conditional logistic regression, accounting for confounding and multiple comparisons. Proteins considered as associated with endometrial cancer risk were further tested in a two-sample Mendelian randomization (MR) analysis using summary data from the UK Biobank (n = 52,363) and the Endometrial Cancer Association Consortium (12,270 cases and 46,126 controls). Findings: In the EPIC nested case-control study, IL-6 [OR per NPX (doubling of concentration) = 1.28 (95% confidence interval (CI) 1.03-1.57)], HGF [1.48 (1.06-2.07)], PIK3AP1 [1.22 (1.00-1.50)] and CLEC4G [1.52 (1.00-2.32)] were positively associated; HSD11B1 [0.67 (0.49-0.91)], SCF [0.68 (0.49-0.94)], and CCL25 [0.80 (0.65-0.99)] were inversely associated with endometrial cancer risk; all estimates had multiple comparisons adjusted P-value > 0.05. In complementary MR analysis, IL-6 [OR per inverse-rank normalized NPX = 1.19 (95% CI 1.04-1.36)] and HSD11B1 [0.91 (0.84-0.99)] were associated with endometrial cancer risk. Interpretation: Altered IL-6 signalling and reduced glucocorticoid activity via HSD11B1 might play important roles in endometrial carcinogenesis.
dc.description.sponsorshipThe coordination of EPIC-Europe is financially supported by International Agency for Research on Cancer (IARC) and by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Nationale Contre le Cancer, Institut Gustave-Roussy, Mutuelle Générale de l’Education Nationale (MGEN), Institut National de la Santé et de la Recherche Médicale (INSERM), French National Research Agency (ANR, reference ANR-10-COHO-0006), French Ministry for Higher Education (subsidy 2102918823, 2103236497, and 2103586016) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (C864/A14136 to EPICNorfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (MR/ N003284/1, MC-UU_12015/1 and MC_UU_00006/1 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom). Previous support has come from “Europe against Cancer” Programme of the European Commission (DG SANCO). We thank the Norwegian Institute of Public Health and the Environment (RIVM), Bilthoven, the Netherlands for their contribution and ongoing support to the EPIC Study; Bertrand Hémon for his support with the EPIC database; and all EPIC participants. The authors acknowledge the use of data and biological samples from EPIC-Utrecht (principal investigator: Roel Vermeulen) and EPIC-Norfolk (principal investigator: Nick Wareham). EJC is funded by a National Institute for Health and Care Research (NIHR) Advanced Fellowship (NIHR300650) and the NIHR Manchester Biomedical Research Centre (NIHR203308). TO’M is funded by a National Health and Medical Research Council of Australia (NHMRC) Emerging Leadership Fellowship (APP1173170). Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the Interna
dc.description.versionYes
dc.identifier.citationWang SE, Viallon V, Lee M, Dimou N, Hamilton F, Biessy C, et al. Circulating inflammatory and immune response proteins and endometrial cancer risk: a nested case-control study and Mendelian randomization analyses. EBioMedicine. 2024 Oct;108:105341.
dc.identifier.doi10.1016/j.ebiom.2024.105341
dc.identifier.essn2352-3964
dc.identifier.pmid39278107
dc.identifier.urihttps://hdl.handle.net/10668/24321
dc.issue.number108
dc.journal.titleEBioMedicine
dc.language.isoen
dc.page.number105341
dc.publisherElsevier
dc.relation.projectIDIIG_FULL_2021_008
dc.relation.projectIDINCA_15849
dc.relation.publisherversionhttps://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(24)00377-3/fulltext
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectEndometrial cancer
dc.subjectHSD11B1
dc.subjectInterleukin-6
dc.subjectMendelian randomisation
dc.subjectProteomics
dc.subject.decsNeoplasias endometriales
dc.subject.decsInterleucina-6
dc.subject.decsAnálisis de la Aleatorización Mendeliana
dc.subject.meshEndometrial Neoplasms
dc.subject.meshInterleukin-6
dc.subject.meshMendelian Randomization Analysis
dc.subject.meshProteomics
dc.titleCirculating inflammatory and immune response proteins and endometrial cancer risk: a nested case-control study and Mendelian randomization analyses
dc.typeresearch article
dc.type.hasVersionVoR
dspace.entity.typePublication

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