EBioMedicine (Oct 2024)
Circulating inflammatory and immune response proteins and endometrial cancer risk: a nested case-control study and Mendelian randomization analysesResearch in context
- 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
Affiliations
- Sabrina E. Wang
- International Agency for Research on Cancer, World Health Organization, Lyon, France; Corresponding author.
- Vivian Viallon
- International Agency for Research on Cancer, World Health Organization, Lyon, France
- Matthew Lee
- International Agency for Research on Cancer, World Health Organization, Lyon, France
- Niki Dimou
- International Agency for Research on Cancer, World Health Organization, Lyon, France
- Fergus Hamilton
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Infection Science, North Bristol NHS Trust, Bristol, United Kingdom
- Carine Biessy
- International Agency for Research on Cancer, World Health Organization, Lyon, France
- Tracy O'Mara
- Cancer Research Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia
- Maria Kyrgiou
- Department of Metabolism, Digestion & Reproduction - Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom; West London Gynaecological Cancer Centre, Imperial College Healthcare NHS Trust, London, United Kingdom
- Emma J. Crosbie
- Gynaecological Oncology Research Group, Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary's Hospital, Manchester, United Kingdom; Department of Obstetrics and Gynaecology, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom
- Therese Truong
- Paris-Saclay University, UVSQ, Inserm, Gustave Roussy, CESP, Villejuif, France
- Gianluca Severi
- Paris-Saclay University, UVSQ, Inserm, Gustave Roussy, CESP, Villejuif, France; Department of Statistics, Computer Science, Applications “G. Parenti”, University of Florence, Florence, Italy
- Rudolf Kaaks
- Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
- Renée Turzanski Fortner
- Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany; Department of Research, Cancer Registry of Norway, Norwegian Institute of Public Health, Oslo, Norway
- Matthias B. Schulze
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany
- Benedetta Bendinelli
- Clinical Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy
- Sieri Sabina
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
- Rosario Tumino
- Hyblean Association for Epidemiological Research, Aire Onlus, Ragusa, Italy
- Carlotta Sacerdote
- Unit of Cancer Epidemiology, Città della Salute e della Scienza Hospital, University of Turin and CPO Piemonte, Turin, Italy
- Salvatore Panico
- School of Medicine, Federico II University, Naples, Italy
- Marta Crous-Bou
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO) - Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA
- Maria-Jose Sánchez
- Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria, Granada, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Amaia Aizpurua
- Sub Directorate for Public Health and Addictions of Gipuzkoa, Ministry of Health of the Basque Government, San Sebastian, Spain; Epidemiology of Chronic and Communicable Diseases Group, Biodonostia Health Research Institute, San Sebastián, Spain
- Daniel Rodriguez Palacios
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Murcia Regional Health Council-IMIB, Murcia, Spain
- Marcela Guevara
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Instituto de Salud Pública y Laboral de Navarra, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
- Ruth C. Travis
- Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
- Konstantinos K. Tsilidis
- Cancer Epidemiology and Prevention Research Unit, School of Public Health, Imperial College London, London, United Kingdom; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
- Alicia Heath
- Cancer Epidemiology and Prevention Research Unit, School of Public Health, Imperial College London, London, United Kingdom
- James Yarmolinsky
- Cancer Epidemiology and Prevention Research Unit, School of Public Health, Imperial College London, London, United Kingdom
- Sabina Rinaldi
- International Agency for Research on Cancer, World Health Organization, Lyon, France
- Marc J. Gunter
- International Agency for Research on Cancer, World Health Organization, Lyon, France; Cancer Epidemiology and Prevention Research Unit, School of Public Health, Imperial College London, London, United Kingdom
- Laure Dossus
- International Agency for Research on Cancer, World Health Organization, Lyon, France
- Journal volume & issue
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Vol. 108
p. 105341
Abstract
Summary: 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).
