TY - JOUR
T1 - Alteration of amino acid and biogenic amine metabolism in hepatobiliary cancers
T2 - Findings from a prospective cohort study
AU - Stepien, Magdalena
AU - Duarte-Salles, Talita
AU - Fedirko, Veronika
AU - Floegel, Anne
AU - Barupal, Dinesh Kumar
AU - Rinaldi, Sabina
AU - Achaintre, David
AU - Assi, Nada
AU - Tjønneland, Anne
AU - Overvad, Kim
AU - Bastide, Nadia
AU - Boutron-Ruault, Marie Christine
AU - Severi, Gianluca
AU - Kühn, Tilman
AU - Kaaks, Rudolf
AU - Aleksandrova, Krasimira
AU - Boeing, Heiner
AU - Trichopoulou, Antonia
AU - Bamia, Christina
AU - Lagiou, Pagona
AU - Saieva, Calogero
AU - Agnoli, Claudia
AU - Panico, Salvatore
AU - Tumino, Rosario
AU - Naccarati, Alessio
AU - Bueno-De-Mesquita, H. B.
AU - Peeters, Petra H.
AU - Weiderpass, Elisabete
AU - Quirõs, J. Ramõn
AU - Agudo, Antonio
AU - Sánchez, María José
AU - Dorronsoro, Miren
AU - Gavrila, Diana
AU - Barricarte, Aurelio
AU - Ohlsson, Bodil
AU - Sjöberg, Klas
AU - Werner, Mårten
AU - Sund, Malin
AU - Wareham, Nick
AU - Khaw, Kay Tee
AU - Travis, Ruth C.
AU - Schmidt, Julie A.
AU - Gunter, Marc
AU - Cross, Amanda
AU - Vineis, Paolo
AU - Romieu, Isabelle
AU - Scalbert, Augustin
AU - Jenab, Mazda
N1 - Publisher Copyright:
© 2015 UICC.
PY - 2016/1/15
Y1 - 2016/1/15
N2 - 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. What's new? Perturbations in levels of circulating amino acid metabolites are observed in hepatocellular carcinoma (HCC). Yet it is unclear whether these imbalances are apparent from earlier stages of the disease. In this study nested within a prospective cohort, and based on pre-diagnostically collected blood samples, here the authors show strong HCC risk associations for circulating levels of some aromatic, branched-chain and glucogenic amino acids and biogenic amines. This observation of impaired metabolism in early HCC development may be applied towards further research into the aetiology of, and pathways leading to, this disease.
AB - 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. What's new? Perturbations in levels of circulating amino acid metabolites are observed in hepatocellular carcinoma (HCC). Yet it is unclear whether these imbalances are apparent from earlier stages of the disease. In this study nested within a prospective cohort, and based on pre-diagnostically collected blood samples, here the authors show strong HCC risk associations for circulating levels of some aromatic, branched-chain and glucogenic amino acids and biogenic amines. This observation of impaired metabolism in early HCC development may be applied towards further research into the aetiology of, and pathways leading to, this disease.
KW - amino acids
KW - biliary tract cancers
KW - hepatocellular carcinoma
KW - prospective cohort
KW - targeted metabolomics
UR - http://www.scopus.com/inward/record.url?scp=84955666986&partnerID=8YFLogxK
U2 - 10.1002/ijc.29718
DO - 10.1002/ijc.29718
M3 - Article
C2 - 26238458
AN - SCOPUS:84955666986
SN - 0020-7136
VL - 138
SP - 348
EP - 360
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 2
ER -