Fruit and vegetable consumption in relation to hepatocellular carcinoma in a multi-centre, European cohort study.
BACKGROUND
Vegetable and/or fruit intakes in association with hepatocellular carcinoma (HCC) risk have been investigated in case-control studies conducted in specific European countries and cohort studies conducted in Asia, with inconclusive results. No multi-centre European cohort has investigated the indicated associations.


METHODS
In 486,799 men/women from the European Prospective Investigation into Cancer and nutrition, we identified 201 HCC cases after 11 years median follow-up. We calculated adjusted hazard ratios (HRs) for HCC incidence for sex-specific quintiles and per 100 g d(-1) increments of vegetable/fruit intakes.


RESULTS
Higher vegetable intake was associated with a statistically significant, monotonic reduction of HCC risk: HR (100 g d(-1) increment): 0.83; 95% CI: 0.71-0.98. This association was consistent in sensitivity analyses with no apparent heterogeneity across strata of HCC risk factors. Fruit intake was not associated with HCC incidence: HR (100 g d(-1) increment): 1.01; 95% CI: 0.92-1.11.


CONCLUSIONS
Vegetable, but not fruit, intake is associated with lower HCC risk with no evidence for heterogeneity of this association in strata of important HCC risk factors. Mechanistic studies should clarify pathways underlying this association. Given that HCC prognosis is poor and that vegetables are practically universally accessible, our results may be important, especially for those at high risk for the disease.
Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens 115 27, Greece.
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Bamia
1] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens 115 27, Greece [2] Department of Epidemiology, Harvard School of Public Health, 02115 Boston, MA, USA [3] Bureau of Epidemiologic Research, Academy of Athens, Athens 106 79, Greece.
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Lagiou
International Agency for Research on Cancer (IARC-WHO), 69372 Lyon, France.
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Jenab
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal 14558, Germany.
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Aleksandrova
Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta 30322, GA, USA.
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Fedirko
1] Department of Epidemiology, Harvard School of Public Health, 02115 Boston, MA, USA [2] Bureau of Epidemiologic Research, Academy of Athens, Athens 106 79, Greece [3] Hellenic Health Foundation, Athens 115 27, Greece.
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Trichopoulos
Department of Public Health, Section for Epidemiology, Aarhus University, DK-8000 Aarhus C, Denmark.
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Overvad
Danish Cancer Society Research Center, DK-2100 Copenhagen, Denmark.
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Tjønneland
Danish Cancer Society Research Center, DK-2100 Copenhagen, Denmark.
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Olsen
1] Inserm, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health Team, Villejuif, F-94805 Paris, France [2] Paris South University, UMRS 1018, Villejuif, F-94805 Paris, France [3] IGR, Villejuif, F-94805 Paris, France.
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Clavel-Chapelon
1] Inserm, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health Team, Villejuif, F-94805 Paris, France [2] Paris South University, UMRS 1018, Villejuif, F-94805 Paris, France [3] IGR, Villejuif, F-94805 Paris, France.
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Boutron-Ruault
1] Inserm, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health Team, Villejuif, F-94805 Paris, France [2] Paris South University, UMRS 1018, Villejuif, F-94805 Paris, France [3] IGR, Villejuif, F-94805 Paris, France.
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Kvaskoff
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
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Katzke
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
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Kühn
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal 14558, Germany.
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Boeing
Department of Nutrition and Food Sciences, University of Bonn, 53111 Bonn, Germany.
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Nöthlings
Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, 50139 Florence, Italy.
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Palli
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.
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Sieri
Dipartimento di Medicina Clinica e Chirurgia Federico II University, 80131 Naples, Italy.
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Panico
Cancer Registry and Histopathology Unit, 'Civic-M.P. Arezzo' Hospital, ASP 97100 Ragusa, Italy.
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Tumino
HuGeF-Human Genetics Foundation-Torino Molecular and Genetic Epidemiology Unit, 10126 Torino, Italy.
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Naccarati
1] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, The Netherlands [2] Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, 3508 GA Utrecht, The Netherlands [3] Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia [4] Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College, W2 1NY UK London, UK.
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Bueno-de-Mesquita
1] Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College, W2 1NY UK London, UK [2] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.
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Peeters
1] Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, N-9037 Tromsø, Norway [2] Cancer Registry of Norway, NO-0304 Oslo, Norway [3] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-171 Stockholm, Sweden [4] Department of Genetic Epidemiology, Folkhälsan Research Center, 00250 Helsinki, Finland.
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Weiderpass
Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, N-9037 Tromsø, Norway.
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Skeie
Public Health Directorate, CP 33006 Oviedo, Asturias, Spain.
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Quirós
Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), 08908 Barcelona, Spain.
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Agudo
1] Epidemiology Department, Murcia Regional Health Council, E-30008 Murcia, Spain [2] CIBER Epidemiology and Public Health CIBERESP, 28029 Madrid, Spain.
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Chirlaque
1] CIBER Epidemiology and Public Health CIBERESP, 28029 Madrid, Spain [2] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs, GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, 18080 Granada, Spain.
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Sanchez
1] CIBER Epidemiology and Public Health CIBERESP, 28029 Madrid, Spain [2] Navarre Public Health Institute, 31003 Pamplona, Spain.
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Ardanaz
1] Basque Regional Health Department, Public Health Direction, 4-20013 Donostia, San Sebastian, Spain [2] Biodonostia Research Institute CIBER Epidemiology and Public Health CIBERESP, s/n 20014 San Sebastian, Spain.
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Dorronsoro
Diabetes and Cardiovascular disease, Genetic Epidemiology Department of Clinical Sciences in Malmö Lund University, SE-205 92 Malmo, Sweden.
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Ericson
1] Department of Nutritional Research, Public Health and Clinical Medicine, Umeå University, SE-901 85 Umeå, Sweden [2] Arcum, Arctic Research Centre at Umeå University, SE-901 85 Umeå, Sweden.
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Nilsson
Department of Nutritional Research, Public Health and Clinical Medicine, Umeå University, SE-901 85 Umeå, Sweden.
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Wennberg
University of Cambridge, CB2 0SR Cambridge, UK.
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Khaw
1] University of Cambridge, CB2 0SR Cambridge, UK [2] MRC Epidemiology Unit, CB2 0QQ Cambridge, UK.
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Wareham
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, OX3 7LF Oxford, UK.
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Key
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, OX3 7LF Oxford, UK.
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Travis
International Agency for Research on Cancer (IARC-WHO), 69372 Lyon, France.
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Ferrari
International Agency for Research on Cancer (IARC-WHO), 69372 Lyon, France.
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Stepien
International Agency for Research on Cancer (IARC-WHO), 69372 Lyon, France.
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Duarte-Salles
Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College, W2 1NY UK London, UK.
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Norat
Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College, W2 1NY UK London, UK.
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Murphy
Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College, W2 1NY UK London, UK.
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Riboli
1] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens 115 27, Greece [2] Hellenic Health Foundation, Athens 115 27, Greece.
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Trichopoulou
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000209:etiology; D016022:Case-Control Studies; D015331:Cohort Studies; D004032:Diet / Q000706:statistics & numerical data*; D005060:Europe / Q000453:epidemiology; D005260:Female; D005638:Fruit; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014675:Vegetables