Aleksandrova Krasimira, Bamia Christina, Drogan Dagmar, Lagiou Pagona, Trichopoulou Antonia, Jenab Mazda, Fedirko Veronika, Romieu Isabelle, Bueno-de-Mesquita H Bas, Pischon Tobias, Tsilidis Kostas, Overvad Kim, Tjønneland Anne, Bouton-Ruault Marie-Christine, Dossus Laure, Racine Antoine, Kaaks Rudolf, Kühn Tilman, Tsironis Christos, Papatesta Eleni-Maria, Saitakis George, Palli Domenico, Panico Salvatore, Grioni Sara, Tumino Rosario, Vineis Paolo, Peeters Petra H, Weiderpass Elisabete, Lukic Marko, Braaten Tonje, Quirós J Ramón, Luján-Barroso Leila, Sánchez María-José, Chilarque Maria-Dolores, Ardanas Eva, Dorronsoro Miren, Nilsson Lena Maria, Sund Malin, Wallström Peter, Ohlsson Bodil, Bradbury Kathryn E, Khaw Kay-Tee, Wareham Nick, Stepien Magdalena, Duarte-Salles Talita, Assi Nada, Murphy Neil, Gunter Marc J, Riboli Elio, Boeing Heiner, Trichopoulos Dimitrios
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany;
WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece; Hellenic Health Foundation, Athens, Greece;
Am J Clin Nutr. 2015 Dec;102(6):1498-508. doi: 10.3945/ajcn.115.116095. Epub 2015 Nov 11.
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.
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).
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.
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.
These data suggest that the inverse association of coffee intake with HCC risk was partly accounted for by biomarkers of inflammation and hepatocellular injury.
据称，咖啡摄入量较高与肝癌风险较低有关。然而，这种关联是否可由特定生物学机制解释仍不清楚。
我们旨在评估炎症、代谢、肝损伤和铁代谢生物标志物在咖啡摄入量与肝癌主要类型——肝细胞癌（HCC）之间关联中的潜在中介作用。
我们在欧洲癌症与营养前瞻性调查中开展了一项前瞻性巢式病例对照研究，采用发病密度抽样程序，选取125例HCC新发病例，并匹配250例对照。通过多变量调整的条件逻辑回归评估咖啡摄入量与HCC风险的关联，该回归考虑了吸烟、饮酒、肝炎感染及其他既定的肝癌风险因素。基于在单独和联合调整生物标志物的模型中估计回归系数的百分比变化及相关95%置信区间，评估21种生物标志物的中介作用。
与每天饮用咖啡少于2杯（300毫升）相比，每天饮用≥4杯（600毫升）咖啡的多变量调整相对危险度为0.25（95%置信区间：0.11, 0.62；P趋势 = 0.006）。对于炎症生物标志物白细胞介素-6（IL-6）以及肝细胞损伤生物标志物谷氨酸脱氢酶、丙氨酸氨基转移酶、天冬氨酸氨基转移酶（AST）、γ-谷氨酰转移酶（GGT）和总胆红素，证实咖啡摄入量与HCC风险之间的关联有统计学显著减弱，进而怀疑存在中介作用，这些生物标志物联合起来使回归系数减弱了72%（95%置信区间：7%, 239%）。在所研究的生物标志物中，IL-6、AST和GGT使回归系数变化最大，分别为40%、56%和60%。
这些数据表明，咖啡摄入量与HCC风险之间的负相关部分可由炎症和肝细胞损伤生物标志物解释。
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