• Anne Fages, Talita Duarte-Salles, Magdalena Stepien, Pietro Ferrari, Veronika Fedirko, Clément Pontoizeau, Antonia Trichopoulou, Krasimira Aleksandrova, Anne Tjønneland, Anja Olsen, Françoise Clavel-Chapelon, Marie-Christine Boutron-Ruault, Gianluca Severi, Rudolf Kaaks, Tilman Kuhn, Anna Floegel, Heiner Boeing, Pagona Lagiou, Christina Bamia, Dimitrios Trichopoulos, Domenico Palli, Valeria Pala, Salvatore Panico, Rosario Tumino, Paolo Vineis, H Bas Bueno-de-Mesquita, Petra H Peeters, Elisabete Weiderpass, Antonio Agudo, Esther Molina-Montes, José María Huerta, Eva Ardanaz, Miren Dorronsoro, Klas Sjöberg, Bodil Ohlsson, Kay-Tee Khaw, Nick Wareham, Ruth C Travis, Julie A Schmidt, Amanda Cross, Marc Gunter, Elio Riboli, Augustin Scalbert, Isabelle Romieu, Benedicte Elena-Herrmann, and Mazda Jenab.
• 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.
• Bmc Med. 2015 Sep 23; 13: 242242.

BackgroundHepatocellular 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.MethodsTo 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.ResultsA 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.ConclusionOur 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.

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