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

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 PapatestaGeorge 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

Research output: Contribution to journalArticle

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 multivariableadjusted 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 (600mL) 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), g-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.

Original languageEnglish
Pages (from-to)1498-1508
Number of pages11
JournalAmerican Journal of Clinical Nutrition
Volume102
Issue number6
DOIs
Publication statusPublished - Dec 1 2015

Keywords

  • Biomarkers
  • Coffee
  • European Prospective Investigation into Cancer and Nutrition
  • Liver cancer
  • Mediation

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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    Aleksandrova, K., Bamia, C., Drogan, D., Lagiou, P., Trichopoulou, A., Jenab, M., Fedirko, V., Romieu, I., Bueno-De-Mesquita, H. B., Pischon, T., Tsilidis, K., Overvad, K., Tjønneland, A., Bouton-Ruault, M. C., Dossus, L., Racine, A., Kaaks, R., Kühn, T., Tsironis, C., ... Trichopoulos, D. (2015). 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. American Journal of Clinical Nutrition, 102(6), 1498-1508. https://doi.org/10.3945/ajcn.115.116095