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Am J Clin Nutr. 2015 Dec;102(6):1498-508. doi: 10.3945/ajcn.115.116095. Epub 2015 Nov 11.

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.

Author information

  • 1Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany; krasimira.aleksandrova@dife.de.
  • 2WHO 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;
  • 3Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany;
  • 4WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece; Department of Epidemiology, Harvard School of Public Health, Boston, MA; Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece;
  • 5International Agency for Research on Cancer, Lyon, France;
  • 6Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA; Winship Cancer Institute, Emory University, Atlanta, GA;
  • 7National Institute for Public Health and the Environment, Bilthoven, Netherlands; Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, Netherlands; Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom; Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia;
  • 8Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine, Berlin-Buch, Germany;
  • 9Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, University Campus, Ioannina, Greece;
  • 10Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark;
  • 11Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark;
  • 12Inserm, Centre for Research in Epidemiology and Population Health, Nutrition, Hormones and Women's Health Team, Villejuif, France; University Paris Sud, Villejuif, France; IGR, Villejuif, France;
  • 13Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany;
  • 14Hellenic Health Foundation, Athens, Greece;
  • 15Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy;
  • 16Department of Clinical and Experimental Medicine-Federico II University, Naples, Italy;
  • 17Epidemiology and Prevention Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy;
  • 18Cancer Registry and Histopathology Unit, "M.P. Arezzo" Hospital, Ragusa, Italy;
  • 19Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom; HuGeF Foundation, Turin, Italy;
  • 20Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom; Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, Netherlands;
  • 21Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway; Department of Research, Cancer Registry of Norway, Oslo, Norway; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland;
  • 22Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway;
  • 23Public Health Directorate, Asturias, Oviedo, Spain;
  • 24Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, Barcelona, Spain;
  • 25CIBER de Epidemiología y Salud Pública, Spain; Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain;
  • 26CIBER de Epidemiología y Salud Pública, Spain; Department of Epidemiology, Murcia Regional Health Authority, IMIB-Arrixaca, Murcia, Spain;
  • 27CIBER de Epidemiología y Salud Pública, Spain; Navarre Public Health Institute, Pamplona, Spain;
  • 28Epidemiology and Health Information, Public Health Division of Gipuzkoa, Basque Regional Health Department, San Sebastian, Spain;
  • 29Arctic Research Centre, Umeå University, Umeå, Sweden;
  • 30Department of Surgical and Perioperative Sciences, Surgery and Public Health, Nutrition Research, Umeå University, Umeå, Sweden;
  • 31Department of Clinical Sciences, Lund University, Clinical Research Center, Malmö, Sweden;
  • 32Department of Clinical Science, Division of Internal Medicine, Skane University Hospital, Malmö, Lund University, Malmö, Sweden;
  • 33Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom;
  • 34Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; and.
  • 35MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom.
  • 36Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom;
  • 37Hellenic Health Foundation, Athens, Greece; Department of Epidemiology, Harvard School of Public Health, Boston, MA; Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece;

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.

KEYWORDS:

European Prospective Investigation into Cancer and Nutrition; biomarkers; coffee; liver cancer; mediation

PMID:
26561631
[PubMed - indexed for MEDLINE]
PMCID:
PMC4658462
Free PMC Article
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