Mediation analysis of the alcohol‐postmenopausal breast cancer relationship by sex hormones in the EPIC cohort
Year: 2019
Type: article
Abstract: Alcohol consumption is associated with higher risk of breast cancer (BC); however, the biological mechanisms underlying this association are not fully elucidated, particularly the extent to which this relationship is mediated by sex hormone levels. Circulating concentrations of estradiol, testosterone, their free fractions and sex-hormone binding globulin (SHBG), were examined in 430 incident BC cases and 645 matched controls among alcohol-consuming postmenopausal women nested within the European Prospective Investigation into Cancer and Nutrition. Mediation analysis was applied to assess whether individual hormone levels mediated the relationship between alcohol intake and BC risk. An alcohol-related hormonal signature, obtained by partial least square (PLS) regression, was evaluated as a potential mediator. Total (TE), natural direct and natural indirect effects (NIE) were estimated. Alcohol intake was positively associated with overall BC risk and specifically with estrogen receptor-positive tumors with respectively TE = 1.17(95%CI: 1.01,1.35) and 1.36(1.08,1.70) for a 1-standard deviation (1-SD) increase of intake. There was no evidence of mediation by sex steroids or SHBG separately except for a weak indirect effect through free estradiol where NIE = 1.03(1.00,1.06). However, an alcohol-related hormonal signature negatively associated with SHBG and positively with estradiol and testosterone was associated with BC risk (odds ratio [OR] = 1.25 [1.07,1.47]) for a 1-SD higher PLS score, and had a statistically significant NIE accounting for a mediated proportion of 24%. There was limited evidence of mediation of the alcohol-BC association by individual sex hormones. However, a hormonal signature, reflecting lower levels of SHBG and higher levels of sex steroids, mediated a substantial proportion of the association.
Source: International Journal of Cancer
DOI: 10.1002/ijc.32324
Authors: Nada Assi, Sabina Rinaldi, Vivian Viallon, S. Ghazaleh Dashti, Laure Dossus, Agnès Fournier, Iris Cervenka, Marina Kvaskoff, Renée Turzanski‐Fortner, Manuela Bergmann, Heiner Boeing, Salvatore Panico, Fulvio Ricceri, Domenico Palli, Rosario Tumino, Sara Grioni, María José Sánchez Pérez, María‐Dolores Chirlaque, Catalina Bonet, Aurelio Barricarte Gurrea, Pilar Amiano Etxezarreta, Susana Merino, H. Bas Bueno de Mesquita, Carla H. van Gils, Charlotte Onland‐Moret, Anne Tjønneland, Kim Overvad, Antonia Trichopoulou, Georgia Martimianaki, Anna Karakatsani, Tim Key, Sofia Christakoudi, Merete Ellingjord‐Dale, Kostas Tsilidis, Elio Riboli, Rudolf Kaaks, Marc J Gunter, Pietro Ferrari
Institutions: Centre international de recherche sur le cancer, The University of Melbourne, Inserm, Université de Versailles Saint-Quentin-en-Yvelines, Université Paris-Saclay, Institut Gustave Roussy, Centre de recherche en Epidémiologie et Santé des Populations, German Cancer Research Center, German Institute of Human Nutrition, Federico II University Hospital, University of Naples Federico II, University of Turin, Fondazione IRCCS Istituto Nazionale dei Tumori, Universidad de Granada, Instituto de Investigación Biosanitaria de Granada, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Andalusian School of Public Health, Instituto Murciano de Investigación Biosanitaria, Universidad de Murcia, Institut Català d'Oncologia, Instituto de Salud Pública de Navarra, Navarre Institute of Health Research, Biogipuzkoa Health Research Institute, Gobierno del Principado de Asturias, University Medical Center Utrecht, University of Malaya, National Institute for Public Health and the Environment, Imperial College London, University of Copenhagen, Danish Cancer Society, Aarhus University, Hellenic Health Foundation, National and Kapodistrian University of Athens, University General Hospital Attikon, University of Oxford, King's College London, University of Ioannina
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: World Health Organization, Kræftens Bekæmpelse, Deutsches Krebsforschungszentrum, Centre International de Recherche sur le Cancer, Cancer Research UK, National Institute for Health and Care Research, Deutsche Forschungsgemeinschaft, Institut National de la Santé et de la Recherche Médicale, Bundesministerium für Bildung und Forschung, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, Ligue Contre le Cancer, Fondation de France, Consiglio Nazionale delle Ricerche, Associazione Italiana per la Ricerca sul Cancro, Deutsche Krebshilfe, Mutuelle Générale de l'Education Nationale, Health Research Fund of Central Denmark Region, Medical Research Council, World Cancer Research Fund, Directorate-General for Health and Food Safety, National Cancer Institute
OpenAlex ID: W2937954440