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

Stepien, Magdalena ; Duarte-Salles, Talita ; Fedirko, Veronika ; Floegel, Anne ; Barupal, Dinesh Kumar ; Rinaldi, Sabina ; Achaintre, David ; Assi, Nada ; Tjønneland, Anne and Overvad, Kim , et al. (2016) In International Journal of Cancer 138(2). p.348-360
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;... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
International Journal of Cancer
volume
138
issue
2
pages
348 - 360
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:26238458
  • wos:000369161200010
  • scopus:84955666986
  • pmid:26238458
ISSN
0020-7136
DOI
10.1002/ijc.29718
language
English
LU publication?
yes
id
e6e1571f-8de5-4dd3-8d84-d5cd71d6ff90 (old id 7844803)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26238458?dopt=Abstract
date added to LUP
2016-04-01 10:26:17
date last changed
2023-03-17 05:10:33
@article{e6e1571f-8de5-4dd3-8d84-d5cd71d6ff90,
  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.}},
  author       = {{Stepien, Magdalena and Duarte-Salles, Talita and Fedirko, Veronika and Floegel, Anne and Barupal, Dinesh Kumar and Rinaldi, Sabina and Achaintre, David and Assi, Nada and Tjønneland, Anne and Overvad, Kim and Bastide, Nadia and Boutron-Ruault, Marie-Christine and Severi, Gianluca and Kühn, Tilman and Kaaks, Rudolf and Aleksandrova, Krasimira and Boeing, Heiner and Trichopoulou, Antonia and Bamia, Christina and Lagiou, Pagona and Saieva, Calogero and Agnoli, Claudia and Panico, Salvatore and Tumino, Rosario and Naccarati, Alessio and Bueno-de-Mesquita, H B As and Peeters, Petra H and Weiderpass, Elisabete and Quirós, J Ramón and Agudo, Antonio and Sánchez, María-José and Dorronsoro, Miren and Gavrila, Diana and Barricarte, Aurelio and Ohlsson, Bodil and Sjöberg, Klas and Werner, Mårten and Sund, Malin and Wareham, Nick and Khaw, Kay-Tee and Travis, Ruth C and Schmidt, Julie A and Gunter, Marc and Cross, Amanda and Vineis, Paolo and Romieu, Isabelle and Scalbert, Augustin and Jenab, Mazda}},
  issn         = {{0020-7136}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{348--360}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{International Journal of Cancer}},
  title        = {{Alteration of amino acid and biogenic amine metabolism in hepatobiliary cancers: Findings from a prospective cohort study.}},
  url          = {{http://dx.doi.org/10.1002/ijc.29718}},
  doi          = {{10.1002/ijc.29718}},
  volume       = {{138}},
  year         = {{2016}},
}