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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

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Item Type:Article
Title: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
Creators Name:Aleksandrova, K. and Bamia, C. and Drogan, D. and Lagiou, P. and Trichopoulou, A. and Jenab, M. and Fedirko, V. and Romieu, I. and Bueno-de-Mesquita, H.B. and Pischon, T. and Tsilidis, K. and Overvad, K. and Tjønneland, A. and Bouton-Ruault, M.C. and Dossus, L. and Racine, A. and Kaaks, R. and Kuehn, T. and Tsironis, C. and Papatesta, E.M. and Saitakis, G. and Palli, D. and Panico, S. and Grioni, S. and Tumino, R. and Vineis, P. and Peeters, P.H. and Weiderpass, E. and Lukic, M. and Braaten, T. and Quirós, J.R. and Luján-Barroso, L. and Sánchez, M.J. and Chilarque, M.D. and Ardanas, E. and Dorronsoro, M. and Nilsson, L.M. and Sund, M. and Wallström, P. and Ohlsson, B. and Bradbury, K.E. and Khaw, K.T. and Wareham, N. and Stepien, M. and Duarte-Salles, T. and Assi, N. and Murphy, N. and Gunter, M.J. and Riboli, E. and Boeing, H. and Trichopoulos, D.
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), gamma-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.
Keywords:Biomarkers, Coffee, European Prospective Investigation into Cancer and Nutrition, Liver Cancer, Mediation
Source:American Journal of Clinical Nutrition
ISSN:0002-9165
Publisher:American Society for Nutrition
Volume:102
Number:6
Page Range:1498-1508
Date:December 2015
Official Publication:https://doi.org/10.3945/ajcn.115.116095
PubMed:View item in PubMed

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