Alteration of amino acid and biogenic amine metabolism in hepatobiliary cancers: Findings from a prospective cohort study

Year: 2015

Type: article

Abstract: Perturbations in levels of amino acids (AA) and their derivatives are observed in hepatocellular carcinoma (HCC). Yet, it is unclear whether these alterations precede or are a consequence of the disease, nor whether they pertain to anatomically related cancers of the intrahepatic bile duct (IHBC), and gallbladder and extrahepatic biliary tract (GBTC). Circulating standard AA, biogenic amines and hexoses were measured (Biocrates AbsoluteIDQ-p180Kit) in a case-control study nested within a large prospective cohort (147 HCC, 43 IHBC and 134 GBTC cases). Liver function and hepatitis status biomarkers were determined separately. Multivariable conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI) for log-transformed standardised (mean = 0, SD = 1) serum metabolite levels and relevant ratios in relation to HCC, IHBC or GBTC risk. Fourteen metabolites were significantly associated with HCC risk, of which seven metabolites and four ratios were the strongest predictors in continuous models. Leucine, lysine, glutamine and the ratio of branched chain to aromatic AA (Fischer's ratio) were inversely, while phenylalanine, tyrosine and their ratio, glutamate, glutamate/glutamine ratio, kynurenine and its ratio to tryptophan were positively associated with HCC risk. Confounding by hepatitis status and liver enzyme levels was observed. For the other cancers no significant associations were observed. In conclusion, imbalances of specific AA and biogenic amines may be involved in HCC development.

Source: International Journal of Cancer

DOI: 10.1002/ijc.29718

Authors: Magdalena Stepien, Talita Duarte‐Salles, Veronika Fedirko, Anne Floegel, Dinesh Kumar Barupal, Sabina Rinaldi, David Achaintre, Nada Assi, Anne Tjønneland, Kim Overvad, Nadia Bastide, Marie‐Christine Boutron‐Ruault, Gianluca Severi, Tilman Kühn, Rudolf Kaaks, Krasimira Aleksandrova, Heiner Boeing, Antonia Trichopoulou, Christina Bamia, Pagona Lagiou, Calogero Saieva, Claudia Agnoli, Salvatore Panico, Rosario Tumino, Alessio Naccarati, H. B(as). Bueno‐de‐Mesquita, Petra H. Peeters, Elisabete Weiderpass, J. Ramón Quirós, Antonio Agudo, María‐José Sánchez, Miren Dorronsoro, Diana Gavrila, Aurelio Barricarte, Bodil Ohlsson, Klas Sjöberg, Mårten Werner, Malin Sund, Nick Wareham, Kay‐Tee Khaw, Ruth C. Travis, Julie A. Schmidt, Marc Gunter, Amanda Cross, Paolo Vineis, Isabelle Romieu, Augustin Scalbert, Mazda Jenab

Institutions: Centre international de recherche sur le cancer, Emory University, Winship Cancer Institute, German Institute of Human Nutrition, Danish Cancer Society, Aarhus University, Université Paris-Sud, Inserm, Institut Gustave Roussy, Centre de recherche en Epidémiologie et Santé des Populations, Italian institute for Genomic Medicine, German Cancer Research Center, Academy of Athens, Hellenic Health Foundation, National and Kapodistrian University of Athens, Harvard University, Istituto per lo Studio e la Prevenzione Oncologica, Fondazione IRCCS Istituto Nazionale dei Tumori, Federico II University Hospital, University of Naples Federico II, Azienda Usl 8 Arezzo, University Medical Center Utrecht, University of Malaya, National Institute for Public Health and the Environment, Imperial College London, Karolinska Institutet, Cancer Registry of Norway, Folkhälsans Forskningscentrum, UiT The Arctic University of Norway, Gobierno del Principado de Asturias, Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, Universidad de Granada, Instituto de Investigación Biosanitaria de Granada, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Andalusian School of Public Health, Biogipuzkoa Health Research Institute, Instituto Murciano de Investigación Biosanitaria, Skåne University Hospital, Lund University, Umeå University, University of Cambridge, MRC Epidemiology Unit, University of Oxford

Language: English

Topic: Metabolomics and Mass Spectrometry Studies

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

OpenAlex ID: W2171538199