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

• Type of Material: Article
• Authors: Krasimira Aleksandrova, German Institute of Human Nutrition Potsdam-Rehbrücke; Christina Bamia, University of Athens; Dagmar Drogan, German Institute of Human Nutrition Potsdam-Rehbrücke; Pagona Lagiou, University of Athens; Antonia Trichopoulou, University of Athens; Mazda Jenab, International Agency for Research on Cancer; Veronika Fedirko, Emory University; Isabelle Romieu, International Agency for Research on Cancer; H Bas Bueno-de-Mesquita, National Institute for Public Health and the Environment, Netherlands; Tobias Pischon, Max Delbrueck Center for Molecular Medicine; Kostas T Tsilidis, University of Ioannina; Kim Overvad, Aarhus University; Anne Tjønneland, Danish Cancer Society Research Center; Marie-Christine Bouton-Ruault, Institut national de la santé et de la recherche médicale, France; Laure Dossus, Institut national de la santé et de la recherche médicale, France; Antoine Racine, Institut national de la santé et de la recherche médicale, France; Rudolf Kaaks, German Cancer Research Centre; Tilman Kühn, German Cancer Research Centre; Christos Tsironis, Hellenic Health Foundation; Eleni-Maria Papatesta, Hellenic Health Foundation; George Saitakis, Hellenic Health Foundation; Domenico Palli, Cancer Research and Prevention Institute–ISPO; Salvatore Panico, Federico II University; Sara Grioni, Istituto Nazionale dei Tumori; Rosario Tumino, "M.P. Arezzo” Hospital; Paolo Vineis, Imperial College London; Petra H Peeters, Imperial College London; Elisabete Weiderpass, University of Tromsø; Marko Lukic, University of Tromsø; Tonje Braaten, University of Tromsø; J Ramón Quirós, Public Health Directorate; Leila Luján-Barroso, Public Health Directorate, Spain; María-José Sánchez, CIBER de Epidemiología y Salud Pública; Maria-Dolores Chilarque, CIBER de Epidemiología y Salud Pública; Eva Ardanas, CIBER de Epidemiología y Salud Pública; Miren Dorronsoro, Basque Regional Health Department, Spain; Lena Maria Nilsson, Umeå University; Malin Sund, Umeå University; Peter Wallström, Lund University; Bodil Ohlsson, Lund University; Kathryn E Bradbury, University of Oxford; Kay-Tee Khaw, University of Cambridge; Nick Wareham, Addenbrooke’s Hospital; Magdalena Stepien, International Agency for Research on Cancer; Talita Duarte-Salles, International Agency for Research on Cance; Nada Assi, International Agency for Research on Cance; Neil Murphy, Imperial College London; Marc J Gunter, Imperial College London; Elio Riboli, Imperial College London; Heiner Boeing, German Institute of Human Nutrition Potsdam-Rehbrücke; Dimitrios Trichopoulos, Hellenic Health Foundation
• Language: English
• Date: 2015-12-01
• Publisher: American Society for Nutrition
• Publication Version: Final Published Version
• Copyright Statement: © 2015, American Society for Nutrition
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.3945/ajcn.115.116095
• Title of Journal or Parent Work: American Journal of Clinical Nutrition
• ISSN: 0002-9165
• Volume: 102
• Issue: 6
• Start Page: 1498
• End Page: 1508
• Keywords: liver cancer; biomarkers; European Prospective Investigation into Cancer and Nutrition; mediation; coffee
• Research Categories: Health Sciences, Oncology; Health Sciences, Nutrition; Health Sciences, Epidemiology

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.