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BMC Med. 2015 Sep 23;13:242. doi: 10.1186/s12916-015-0462-9.

Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort.

Author information

1
Institut des Sciences Analytiques, Centre de RMN à très hauts champs, CNRS/ENS Lyon/UCB Lyon-1, Université de Lyon, 5 rue de la Doua, 69100, Villeurbanne, France.
2
International Agency for Research on Cancer (IARC-WHO), Lyon, France.
3
Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
4
Hellenic Health Foundation, Alexandroupoleos 23, GR-115 27, Athens, Greece.
5
Bureau of Epidemiologic Research, Academy of Athens, Kaisareias 13, GR-115 27, Athens, Greece.
6
Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbrücke, Germany.
7
Diet, Genes and Environment, Danish Cancer Society Research Center, Strandboulevarden 49, DK 2100, Copenhagen, Denmark.
8
INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health Team, F-94805, Villejuif, France.
9
Université Paris Sud, UMRS 1018, F-94805, Villejuif, France.
10
Institut Gustave Roussy, F-94805, Villejuif, France.
11
Human Genetics Foundation (HuGeF), Torino, Italy.
12
Department of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany.
13
Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, 75 M. Asias, Goudi, GR-115 27, Athens, Greece.
14
Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA.
15
Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy.
16
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milano, Italy.
17
Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
18
Cancer Registry and Histopathology Unit, "Civic - M.P. Arezzo" Hospital, Ragusa, Italy.
19
MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
20
Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
21
Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands.
22
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
23
Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
24
Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
25
Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
26
Department of Research, Cancer Registry of Norway, Oslo, Norway.
27
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
28
Samfundet Folkhälsan, Helsinki, Finland.
29
Unit of Nutrition and Cancer, IDIBELL, Catalan Institute of Oncology-ICO, L'Hospitalet de Llobregat, Barcelona, 08908, Spain.
30
Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
31
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
32
Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
33
Navarre Public Health Institute, Pamplona, Spain.
34
Public Health Direction and Biodonostia CIBERESP, Basque Regional Health Department, San Sebastian, Spain.
35
Department of Clinical Sciences, Lund University, Malmö, Sweden.
36
Department of Gastroenterology and Nutrition, Skåne University Hospital, Malmö, Sweden.
37
Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital, Lund University, Malmö, Sweden.
38
University of Cambridge School of Clinical Medicine, Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge, UK.
39
MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
40
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
41
Institut des Sciences Analytiques, Centre de RMN à très hauts champs, CNRS/ENS Lyon/UCB Lyon-1, Université de Lyon, 5 rue de la Doua, 69100, Villeurbanne, France. benedicte.elena@ens-lyon.fr.
42
International Agency for Research on Cancer (IARC-WHO), Lyon, France. jenabm@iarc.fr.

Abstract

BACKGROUND:

Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is difficult to diagnose and has limited treatment options with a low survival rate. Aside from a few key risk factors, such as hepatitis, high alcohol consumption, smoking, obesity, and diabetes, there is incomplete etiologic understanding of the disease and little progress in identification of early risk biomarkers.

METHODS:

To address these aspects, an untargeted nuclear magnetic resonance metabolomic approach was applied to pre-diagnostic serum samples obtained from first incident, primary HCC cases (n = 114) and matched controls (n = 222) identified from amongst the participants of a large European prospective cohort.

RESULTS:

A metabolic pattern associated with HCC risk comprised of perturbations in fatty acid oxidation and amino acid, lipid, and carbohydrate metabolism was observed. Sixteen metabolites of either endogenous or exogenous origin were found to be significantly associated with HCC risk. The influence of hepatitis infection and potential liver damage was assessed, and further analyses were made to distinguish patterns of early or later diagnosis.

CONCLUSION:

Our results show clear metabolic alterations from early stages of HCC development with application for better etiologic understanding, prevention, and early detection of this increasingly common cancer.

PMID:
26399231
PMCID:
PMC4581424
DOI:
10.1186/s12916-015-0462-9
[Indexed for MEDLINE]
Free PMC Article

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