TY  - JOUR
AU  - Stepien, Magdalena
AU  - Keski-Rahkonen, Pekka
AU  - Kiss, Agneta
AU  - Robinot, Nivonirina
AU  - Duarte-Salles, Talita
AU  - Murphy, Neil
AU  - Perlemuter, Gabriel
AU  - Viallon, Vivian
AU  - Tjønneland, Anne
AU  - Rostgaard-Hansen, Agnetha Linn
AU  - Dahm, Christina C
AU  - Overvad, Kim
AU  - Boutron-Ruault, Marie-Christine
AU  - Mancini, Francesca Romana
AU  - Mahamat-Saleh, Yahya
AU  - Aleksandrova, Krasimira
AU  - Kaaks, Rudolf
AU  - Kühn, Tilman
AU  - Trichopoulou, Antonia
AU  - Karakatsani, Anna
AU  - Panico, Salvatore
AU  - Tumino, Rosario
AU  - Palli, Domenico
AU  - Tagliabue, Giovanna
AU  - Naccarati, Alessio
AU  - Vermeulen, Roel C H
AU  - Bueno-de-Mesquita, H Bas
AU  - Weiderpass, Elisabete
AU  - Skeie, Guri
AU  - Ramón Quirós, J.
AU  - Ardanaz, Eva
AU  - Mokoroa, Olatz
AU  - Sala, Núria
AU  - Sánchez, Maria-Jose
AU  - Huerta, José María
AU  - Winkvist, Anna
AU  - Harlid, Sophia
AU  - Ohlsson, Bodil
AU  - Sjöberg, Klas
AU  - Schmidt, Julie A
AU  - Wareham, Nick
AU  - Khaw, Kay-Tee
AU  - Ferrari, Pietro
AU  - Rothwell, Joseph A
AU  - Gunter, Marc
AU  - Riboli, Elio
AU  - Scalbert, Augustin
AU  - Jenab, Mazda
TI  - Metabolic perturbations prior to hepatocellular carcinoma diagnosis - Findings from a prospective observational cohort study.
JO  - International journal of cancer
VL  - 148
IS  - 3
SN  - 1097-0215
CY  - Bognor Regis
PB  - Wiley-Liss
M1  - DKFZ-2020-01563
SP  - 609-625
PY  - 2020
N1  - 2021 Feb 1;148(3):609-625
AB  - Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective EPIC cohort (>520 000 participants,), where we identified 129 HCC cases matched 1:1 to controls. We conducted high resolution untargeted liquid chromatography-mass spectrometry based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk; 14 of which were unambiguously identified using pure reference standards. Positive HCC risk associations were observed for N1-acetylspermidine, isatin, p-hydroxyphenyllactic acid, tyrosine, sphingosine, L,L-cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid, and 7-methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, γ-carboxyethyl hydroxychroman, and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids, phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development. This article is protected by copyright. All rights reserved.
LB  - PUB:(DE-HGF)16
C6  - pmid:32734650
DO  - DOI:10.1002/ijc.33236
UR  - https://inrepo02.dkfz.de/record/157334
ER  -