The association of coffee intake with liver cancer risk is mediated by biomarkers of inflammation and hepatocellular injury: data from the European Prospective Investigation into Cancer and Nutrition
Year: 2015
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Higher coffee intake has been purportedly related to a lower risk of liver cancer. However, it remains unclear whether this association may be accounted for by specific biological mechanisms. OBJECTIVE: We aimed to evaluate the potential mediating roles of inflammatory, metabolic, liver injury, and iron metabolism biomarkers on the association between coffee intake and the primary form of liver cancer-hepatocellular carcinoma (HCC). DESIGN: We conducted a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition among 125 incident HCC cases matched to 250 controls using an incidence-density sampling procedure. The association of coffee intake with HCC risk was evaluated by using multivariable-adjusted conditional logistic regression that accounted for smoking, alcohol consumption, hepatitis infection, and other established liver cancer risk factors. The mediating effects of 21 biomarkers were evaluated on the basis of percentage changes and associated 95% CIs in the estimated regression coefficients of models with and without adjustment for biomarkers individually and in combination. RESULTS: The multivariable-adjusted RR of having ≥4 cups (600 mL) coffee/d compared with <2 cups (300 mL)/d was 0.25 (95% CI: 0.11, 0.62; P-trend = 0.006). A statistically significant attenuation of the association between coffee intake and HCC risk and thereby suspected mediation was confirmed for the inflammatory biomarker IL-6 and for the biomarkers of hepatocellular injury glutamate dehydrogenase, alanine aminotransferase, aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), and total bilirubin, which-in combination-attenuated the regression coefficients by 72% (95% CI: 7%, 239%). Of the investigated biomarkers, IL-6, AST, and GGT produced the highest change in the regression coefficients: 40%, 56%, and 60%, respectively. CONCLUSION: These data suggest that the inverse association of coffee intake with HCC risk was partly accounted for by biomarkers of inflammation and hepatocellular injury.
Authors: Krasimira Aleksandrova, Christina Bamia, Dagmar Drogan, Pagona Lagiou, Antonia Trichopoulou, Mazda Jenab, Veronika Fedirko, Isabelle Romieu, H Bas Bueno-de-Mesquita, Tobias Pischon, Kostas Tsilidis, Kim Overvad, Anne Tjønneland, Marie-Christine Bouton-Ruault, Laure Dossus, Antoine Racine, Rudolf Kaaks, Tilman Kühn, Christos Tsironis, Eleni-Maria Papatesta, George Saitakis, Domenico Palli, Salvatore Panico, Sara Grioni, Rosario Tumino, Paolo Vineis, Petra H Peeters, Elisabete Weiderpass, Marko Lukic, Tonje Braaten, J Ramón Quirós, Leila Luján-Barroso, María-José Sánchez, Maria-Dolores Chilarque, Eva Ardanas, Miren Dorronsoro, Lena Maria Nilsson, Malin Sund, Peter Wallström, Bodil Ohlsson, Kathryn E Bradbury, Kay-Tee Khaw, Nick Wareham, Magdalena Stepien, Talita Duarte-Salles, Nada Assi, Neil Murphy, Marc J Gunter, Elio Riboli, Heiner Boeing, Dimitrios Trichopoulos
Institutions: German Institute of Human Nutrition, National and Kapodistrian University of Athens, Hellenic Health Foundation, Harvard University, Academy of Athens, Centre international de recherche sur le cancer, Emory University, Winship Cancer Institute, University Medical Center Utrecht, University of Malaya, National Institute for Public Health and the Environment, Imperial College London, Max Delbrück Center, University of Ioannina, Aarhus University, Danish Cancer Society, Université Paris-Sud, Inserm, Centre de recherche en Epidémiologie et Santé des Populations, German Cancer Research Center, Istituto per lo Studio e la Prevenzione Oncologica, Federico II University Hospital, University of Naples Federico II, Fondazione IRCCS Istituto Nazionale dei Tumori, Italian institute for Genomic Medicine, Karolinska Institutet, Cancer Registry of Norway, Folkhälsans Forskningscentrum, UiT The Arctic University of Norway, Gobierno del Principado de Asturias, Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, 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, Lund University, University of Cambridge, University of Oxford, Instituto de Salud Pública de Navarra, Arctic Research Centre, Skåne University Hospital, Umeå University, Basque Government, Addenbrooke's Hospital, MRC Epidemiology Unit
Language: English
Topic: Coffee research and impacts
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $2,922
Funders: World Health Organization, Kræftens Bekæmpelse, Deutsches Krebsforschungszentrum, Centre International de Recherche sur le Cancer, Wellcome Trust, Cancer Research UK, National Institute for Health and Care Research, British Heart Foundation, Food Standards Agency, Stroke Association, European Commission, Deutsche Forschungsgemeinschaft, Institut National de la Santé et de la Recherche Médicale, Bundesministerium für Bildung und Forschung, Cancerfonden, Ligue Contre le Cancer, NordForsk, Deutsche Krebshilfe, Institut National Du Cancer, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, Hellenic Health Foundation, Medical Research Council, World Cancer Research Fund, Health and Medical Research Fund, National Cancer Institute
OpenAlex ID: W2177838855