TY - JOUR
T1 - The association of coffee intake with liver cancer risk is mediated by biomarkers of inflammation and hepatocellular injury
T2 - Data from the European Prospective Investigation into Cancer and Nutrition
AU - Aleksandrova, Krasimira
AU - Bamia, Christina
AU - Drogan, Dagmar
AU - Lagiou, Pagona
AU - Trichopoulou, Antonia
AU - Jenab, Mazda
AU - Fedirko, Veronika
AU - Romieu, Isabelle
AU - Bueno-De-Mesquita, H. Bas
AU - Pischon, Tobias
AU - Tsilidis, Kostas
AU - Overvad, Kim
AU - Tjønneland, Anne
AU - Bouton-Ruault, Marie Christine
AU - Dossus, Laure
AU - Racine, Antoine
AU - Kaaks, Rudolf
AU - Kühn, Tilman
AU - Tsironis, Christos
AU - Papatesta, Eleni Maria
AU - Saitakis, George
AU - Palli, Domenico
AU - Panico, Salvatore
AU - Grioni, Sara
AU - Tumino, Rosario
AU - Vineis, Paolo
AU - Peeters, Petra H.
AU - Weiderpass, Elisabete
AU - Lukic, Marko
AU - Braaten, Tonje
AU - Quirós, J. Ramón
AU - Luján-Barroso, Leila
AU - Sánchez, María José
AU - Chilarque, Maria Dolores
AU - Ardanas, Eva
AU - Dorronsoro, Miren
AU - Maria Nilsson, Lena
AU - Sund, Malin
AU - Wallström, Peter
AU - Ohlsson, Bodil
AU - Bradbury, Kathryn E.
AU - Khaw, Kay Tee
AU - Wareham, Nick
AU - Stepien, Magdalena
AU - Duarte-Salles, Talita
AU - Assi, Nada
AU - Murphy, Neil
AU - Gunter, Marc J.
AU - Riboli, Elio
AU - Boeing, Heiner
AU - Trichopoulos, Dimitrios
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
KW - Biomarkers
KW - Coffee
KW - European Prospective Investigation into Cancer and Nutrition
KW - Liver cancer
KW - Mediation
UR - http://www.scopus.com/inward/record.url?scp=84948799615&partnerID=8YFLogxK
U2 - 10.3945/ajcn.115.116095
DO - 10.3945/ajcn.115.116095
M3 - Article
C2 - 26561631
AN - SCOPUS:84948799615
SN - 0002-9165
VL - 102
SP - 1498
EP - 1508
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
IS - 6
ER -