Adiposity and Endometrial Cancer Risk in Postmenopausal Women: A Sequential Causal Mediation Analysis

S Ghazaleh Dashti; Dallas R English; Julie A Simpson; Amalia Karahalios; Margarita Moreno-Betancur; Carine Biessy; Sabina Rinaldi; Pietro Ferrari; Anne Tjonneland; Jytte Halkjaer; Christina C Dahm; Helene Tilma Vistisen; Florence Menegaux; Vittorio Perduca; Gianluca Severi; Krasimira Aleksandrova; Matthias B Schulze; Giovanna Masala; Sabina Sieri; Rosario Tumino; Alessandra Macciotta; Salvatore Panico; Anouk E Hiensch; Anne M May; J Ramon Quiros; Antonio Agudo; Maria-Jose Sanchez; Pilar Amiano; Sandra Colorado-Yohar; Eva Ardanaz; Naomi E Allen; Elisabete Weiderpass; Renee Turzanski Fortner; Sofia Christakoudi; Konstantinos K Tsilidis; Elio Riboli; Rudolf Kaaks; Marc J Gunter; Vivian Viallon; Laure Dossus

Journal article

Adiposity and Endometrial Cancer Risk in Postmenopausal Women: A Sequential Causal Mediation Analysis

S Ghazaleh Dashti, Dallas R English, Julie A Simpson, Amalia Karahalios, Margarita Moreno-Betancur, Carine Biessy, Sabina Rinaldi, Pietro Ferrari, Anne Tjonneland, Jytte Halkjaer, Christina C Dahm, Helene Tilma Vistisen, Florence Menegaux, Vittorio Perduca, Gianluca Severi, Krasimira Aleksandrova, Matthias B Schulze, Giovanna Masala, Sabina Sieri, Rosario Tumino Show all

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION | AMER ASSOC CANCER RESEARCH | Published : 2021

DOI: 10.1158/1055-9965.EPI-20-0965

Abstract

BACKGROUND: Adiposity increases endometrial cancer risk, possibly through inflammation, hyperinsulinemia, and increasing estrogens. We aimed to quantify the mediating effects of adiponectin (anti-inflammatory adipocytokine); IL6, IL1-receptor antagonist, TNF receptor 1 and 2, and C-reactive protein (inflammatory status biomarkers); C-peptide (hyperinsulinemia biomarker); and free estradiol and estrone (estrogen biomarkers) in the adiposity-endometrial cancer link in postmenopausal women. METHODS: We used data from a case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Eligible women did not have cancer, hysterectomy, and diabetes; did not use ora..

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University of Melbourne Researchers

Emily Karahalios Author Melbourne School of Population and Global Health

Dallas English Author Melbourne School of Population and Global Health

Gianluca Severi Author Melbourne School of Population and Global Health

Margarita Moreno-Betancur Author Paediatrics Royal Children's Hospital

Julie Simpson Author Melbourne School of Population and Global Health

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Grants

Awarded by World Cancer Research Fund

Awarded by Australian National Health and Medical Research Council

Awarded by Australian Research Council - Australian Government

Funding Acknowledgements

This work was supported by the World Cancer Research Fund (grants 2003/18 and 2007/13), Australian National Health and Medical Research Council grants (1150591 to S.G. Dashti and 1104975 to J.A. Simpson), and Melbourne Research Scholarship (to S.G. Dashti). M. Moreno-Betancur is the recipient of an Australian Research Council Discovery Early Career Award (project number DE190101326) funded by the Australian Government. The work reported in this article was undertaken by S.G. Dashti while hosted by the IARC and funded partially by a PhD scholarship by IARC. The coordination of EPIC is financially supported by the European Commission and the IARC. The national cohorts are supported by the following: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, and Institut National de la Sante et de la Recherche Medicale (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and Federal Ministry of Education and Research (Germany); Stavros Niarchos Foundation and Hellenic Health Foundation (Greece); Italian Association for Research on Cancer and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sport, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund, and Statistics Netherlands (the Netherlands); European Research Council and Nordforsk, Nordic Centre of Excellence Programme on Food, Nutrition and Health (Norway); Health Research Fund, Regional Governments of Andalucia, Asturias, Basque Country, Murcia, and Navarra, and Instituto de Salud Carlos III Red Tematica de Investigacion Cooperativa en Salud (Spain); Swedish Cancer Society, Swedish Scientific Council, and Regional Governments of Skane and Vasterbotten (Sweden); and Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (United Kingdom).