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000157334 041__ $$aeng
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000157334 1001_ $$aStepien, Magdalena$$b0
000157334 245__ $$aMetabolic perturbations prior to hepatocellular carcinoma diagnosis - Findings from a prospective observational cohort study.
000157334 260__ $$aBognor Regis$$bWiley-Liss$$c2020
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000157334 500__ $$a2021 Feb 1;148(3):609-625
000157334 520__ $$aHepatocellular 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.
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000157334 7001_ $$aKeski-Rahkonen, Pekka$$b1
000157334 7001_ $$aKiss, Agneta$$b2
000157334 7001_ $$aRobinot, Nivonirina$$b3
000157334 7001_ $$aDuarte-Salles, Talita$$b4
000157334 7001_ $$00000-0003-3347-8249$$aMurphy, Neil$$b5
000157334 7001_ $$aPerlemuter, Gabriel$$b6
000157334 7001_ $$aViallon, Vivian$$b7
000157334 7001_ $$aTjønneland, Anne$$b8
000157334 7001_ $$aRostgaard-Hansen, Agnetha Linn$$b9
000157334 7001_ $$aDahm, Christina C$$b10
000157334 7001_ $$aOvervad, Kim$$b11
000157334 7001_ $$00000-0002-5956-5693$$aBoutron-Ruault, Marie-Christine$$b12
000157334 7001_ $$00000-0003-2297-3869$$aMancini, Francesca Romana$$b13
000157334 7001_ $$aMahamat-Saleh, Yahya$$b14
000157334 7001_ $$aAleksandrova, Krasimira$$b15
000157334 7001_ $$0P:(DE-He78)4b2dc91c9d1ac33a1c0e0777d0c1697a$$aKaaks, Rudolf$$b16$$udkfz
000157334 7001_ $$0P:(DE-He78)0907a10ba1dc8f53f04907f54f6fdcfe$$aKühn, Tilman$$b17$$udkfz
000157334 7001_ $$aTrichopoulou, Antonia$$b18
000157334 7001_ $$aKarakatsani, Anna$$b19
000157334 7001_ $$aPanico, Salvatore$$b20
000157334 7001_ $$aTumino, Rosario$$b21
000157334 7001_ $$aPalli, Domenico$$b22
000157334 7001_ $$aTagliabue, Giovanna$$b23
000157334 7001_ $$aNaccarati, Alessio$$b24
000157334 7001_ $$aVermeulen, Roel C H$$b25
000157334 7001_ $$aBueno-de-Mesquita, H Bas$$b26
000157334 7001_ $$00000-0003-2237-0128$$aWeiderpass, Elisabete$$b27
000157334 7001_ $$aSkeie, Guri$$b28
000157334 7001_ $$aRamón Quirós, J.$$b29
000157334 7001_ $$aArdanaz, Eva$$b30
000157334 7001_ $$aMokoroa, Olatz$$b31
000157334 7001_ $$00000-0003-3585-7613$$aSala, Núria$$b32
000157334 7001_ $$aSánchez, Maria-Jose$$b33
000157334 7001_ $$aHuerta, José María$$b34
000157334 7001_ $$aWinkvist, Anna$$b35
000157334 7001_ $$aHarlid, Sophia$$b36
000157334 7001_ $$aOhlsson, Bodil$$b37
000157334 7001_ $$aSjöberg, Klas$$b38
000157334 7001_ $$00000-0002-7733-8750$$aSchmidt, Julie A$$b39
000157334 7001_ $$aWareham, Nick$$b40
000157334 7001_ $$aKhaw, Kay-Tee$$b41
000157334 7001_ $$aFerrari, Pietro$$b42
000157334 7001_ $$aRothwell, Joseph A$$b43
000157334 7001_ $$aGunter, Marc$$b44
000157334 7001_ $$aRiboli, Elio$$b45
000157334 7001_ $$aScalbert, Augustin$$b46
000157334 7001_ $$00000-0002-0573-1852$$aJenab, Mazda$$b47
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