| Literature DB >> 26238458 |
Magdalena Stepien1, Talita Duarte-Salles1, Veronika Fedirko2, Anne Floegel3, Dinesh Kumar Barupal1, Sabina Rinaldi1, David Achaintre1, Nada Assi1, Anne Tjønneland4, Kim Overvad5, Nadia Bastide6,7,8, Marie-Christine Boutron-Ruault6,7,8, Gianluca Severi9, Tilman Kühn10, Rudolf Kaaks10, Krasimira Aleksandrova3, Heiner Boeing3, Antonia Trichopoulou11,12, Christina Bamia11,13, Pagona Lagiou13,14, Calogero Saieva15, Claudia Agnoli16, Salvatore Panico17, Rosario Tumino18, Alessio Naccarati19, H B As Bueno-de-Mesquita20,21,22,23, Petra H Peeters24, Elisabete Weiderpass25,26,27,28, J Ramón Quirós29, Antonio Agudo30, María-José Sánchez31,32, Miren Dorronsoro33, Diana Gavrila32,34,35, Aurelio Barricarte32,36, Bodil Ohlsson37, Klas Sjöberg38,39, Mårten Werner40, Malin Sund41, Nick Wareham42, Kay-Tee Khaw43, Ruth C Travis44, Julie A Schmidt44, Marc Gunter45, Amanda Cross45, Paolo Vineis45, Isabelle Romieu1, Augustin Scalbert1, Mazda Jenab1.
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.Entities:
Keywords: amino acids; biliary tract cancers; hepatocellular carcinoma; prospective cohort; targeted metabolomics
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Year: 2015 PMID： 26238458 DOI： 10.1002/ijc.29718
Source DB: PubMed Journal: Int J Cancer ISSN： 0020-7136 Impact factor: 7.396