Circulating inflammatory and immune response proteins and endometrial cancer risk: a nested case-control study and Mendelian randomization analyses
Year: 2024
Type: article
Study design: Observational Study
Abstract: BACKGROUND: 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. FUNDING: Funding for IIG_FULL_2021_008 was obtained from Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund International grant programme; Funding for INCA_15849 was obtained from Institut National du Cancer (INCa).
Source: EBioMedicine
Authors: Sabrina E. Wang, Vivian Viallon, Matthew Lee, Niki Dimou, Fergus Hamilton, Carine Biessy, Tracy O'Mara, Maria Kyrgiou, Emma J. Crosbie, Therese Truong, Gianluca Severi, Rudolf Kaaks, Renée Turzanski Fortner, Matthias B. Schulze, Benedetta Bendinelli, Sieri Sabina, Rosario Tumino, Carlotta Sacerdote, Salvatore Panico, Marta Crous-Bou, Maria-Jose Sánchez, Amaia Aizpurua, Daniel Rodriguez Palacios, Marcela Guevara, Ruth C. Travis, Konstantinos K. Tsilidis, Alicia Heath, James Yarmolinsky, Sabina Rinaldi, Marc J. Gunter, Laure Dossus
Institutions: Centre international de recherche sur le cancer, North Bristol NHS Trust, University of Bristol, MRC Integrative Epidemiology Unit, QIMR Berghofer Medical Research Institute, Imperial College Healthcare NHS Trust, Imperial College London, Manchester Academic Health Science Centre, University of Manchester, St Mary's Hospital, Manchester University NHS Foundation Trust, Inserm, Université de Versailles Saint-Quentin-en-Yvelines, Université Paris-Saclay, Institut Gustave Roussy, Centre de recherche en Epidémiologie et Santé des Populations, University of Florence, German Cancer Research Center, Norwegian Institute of Public Health, Cancer Registry of Norway, University of Potsdam, German Institute of Human Nutrition, Fondazione IRCCS Istituto Nazionale dei Tumori, Associazione Iblea per la Ricerca Epidemiologica E.T.S., Piedmont Reference Center for Epidemiology and Cancer Prevention, University of Turin, University of Naples Federico II, Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, Instituto de Investigación Biosanitaria de Granada, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Andalusian School of Public Health, Basque Government, Ministry of Health, Biogipuzkoa Health Research Institute, Instituto Murciano de Investigación Biosanitaria, Instituto de Salud Pública de Navarra, University of Oxford, University of Ioannina
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,000
Funders: World Health Organization, Deutsches Krebsforschungszentrum, World Cancer Research Fund International, Cancer Research UK, National Institute for Health and Care Research, Imperial College London, European Commission, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Bundesministerium für Bildung und Forschung, Cancerfonden, Vetenskapsrådet, Associazione Italiana per la Ricerca sul Cancro, Deutsche Krebshilfe, Institut National Du Cancer, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, Wereld Kanker Onderzoek Fonds, Manchester Biomedical Research Centre, Medical Research Council, World Cancer Research Fund, National Health and Medical Research Council, Instituto de Salud Carlos III, Rijksinstituut voor Volksgezondheid en Milieu, NIHR Imperial Biomedical Research Centre, School of Public Health, Imperial College London, Norwegian Institute of Public Health
Awards: G1028693051, G1071815507, Aetiology of type 2 diabetes and related metabolic disorders, G1173971013, G1192877484, G1257877605, G1265254713, G1313149160, G1437520050, G1483213741, G1691963278, G1798610363, G1819892784, G1851901423, G2042260859, G2055949126, G2185877915, G22324425, G2342228987, G2409987178, G2572521044, G271171424, G2742323354, G2771691379, G2784123474, G2978753608, G300440387, G30665515, G3216658785, G3320100446, G3328679326, G3523705848, G365332712, G367618303, G382879149, G4032711583, G4079049029, G4098851317, G420832550, G4245875310, G4303038735, G4303672817, G4378152838, G4409035895, G4421079832, G4448961366, Health of vegetarians, G4844208673, G4879533352, G4902673736, G493358262, G4968824801, G498571244, G5090410713, G5137858745, G5271742736, G527520901, G5315906942, G5406065712, Etude Epidémiologique des Enfants de femmes de l'Education Nationale, G5748618488, G5783272435, G5885537923, G6153405184, G62261614, G636480517, G6376359690, G6442500046, G6487494159, G6672458653, G6682251940, G6723506513, G6739022024, G6793143258, G6835760186, G6848493935, G6883270616, G6907663651, G6923329853, G7112453972, G7240651115, G7256918494, G7482357016, G7597388277, G7654876629, G7791851099, G7987655622, G8020903098, G8139206928, G8140410841, G8203058914, G821278163, G8279237360, G8368112200, G8377080268, G8439303526, G847199856, G8478113701, G8480575570, G8544555571, Urine testing for cervical screening: is it effective and can it improve uptake?, G8561181082, G8615873201, G8637022941, G8805877516, Leveraging genetic data to understand endometrial cancer, G8817290801, G8846336397, G8917271119, G8959392569, G896962615, G899966268, G97280612
OpenAlex ID: W4402542225