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Metabolic perturbat...
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Stepien, M.International Agency for Research on Cancer, World Health Organization
(author)
Metabolic perturbations prior to hepatocellular carcinoma diagnosis: Findings from a prospective observational cohort study
- Article/chapterEnglish2021
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LIBRIS-ID:oai:gup.ub.gu.se/297800
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https://gup.ub.gu.se/publication/297800URI
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https://doi.org/10.1002/ijc.33236DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-174900URI
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https://lup.lub.lu.se/record/09c34782-6bfd-446b-b2b5-8bde853b96dfURI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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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 European Prospective Investigation into Cancer and Nutrition (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, of which 14 were unambiguously identified using pure reference standards. Positive HCC-risk associations were observed forN1-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, gamma-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 and 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.
Subject headings and genre
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Keski-Rahkonen, P.International Agency for Research on Cancer, World Health Organization
(author)
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Kiss, A.International Agency for Research on Cancer, World Health Organization
(author)
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Robinot, N.International Agency for Research on Cancer, World Health Organization
(author)
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Duarte-Salles, T.Institut Universitari d’Investigació en Atenció Primària Jordi Gol,International Agency for Research on Cancer, World Health Organization
(author)
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Murphy, N.International Agency for Research on Cancer, World Health Organization
(author)
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Perlemuter, G.Antoine-Béclère Hospital,Inflammation, Chimiokines et Immunopathologie (Inserm Umr 996),University of Paris-Saclay
(author)
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Viallon, V.International Agency for Research on Cancer, World Health Organization
(author)
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Tjonneland, A.Danish Cancer Society
(author)
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Rostgaard-Hansen, A. L.Danish Cancer Society
(author)
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Dahm, C. C.Aarhus University
(author)
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Overvad, K.Aarhus University,Aalborg University Hospital
(author)
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Boutron-Ruault, M. C.Centre for Research in Epidemiology and Population Health (CESP),Institut Gustave Roussy
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Mancini, F. R.Institut Gustave Roussy,Centre for Research in Epidemiology and Population Health (CESP)
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Mahannat-Saleh, Y.Centre for Research in Epidemiology and Population Health (CESP),Institut Gustave Roussy
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Aleksandrova, K.German Institute of Human Nutrition
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Kaaks, R.German Cancer Research Centre
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Kühn, TilmanGerman Cancer Research Centre(Swepub:lu)extLU-26
(author)
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Trichopoulou, A.National and Kapodistrian University of Athens,Hellenic Health Foundation, Athens
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Karakatsani, A.Hellenic Health Foundation, Athens,National and Kapodistrian University of Athens
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Panico, S.University of Naples Federico II
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Tumino, R.Provincial Health Authority (ASP) Ragusa
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Palli, D.Cancer Research and Prevention Institute (ISPO)
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Tagliabue, G.Istituto Nazionale dei Tumori
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Naccarati, A.Italian Institute for Genomic Medicine (IIGM)
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Vermeulen, R. C. H.Utrecht University
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Bueno-de-Mesquita, H. B.National Institute for Public Health and the Environment (RIVM),University Medical Center Utrecht,University of Malaya,Imperial College London
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Weiderpass, E.International Agency for Research on Cancer, World Health Organization
(author)
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Skeie, G.UiT The Arctic University of Norway, Tromsø
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Quiros, J. R.Public Health Directorate
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Ardanaz, EvaHealth Research Institute of Navarra (IDISNA),CIBER Epidemiology and Public Health (CIBERESP)(Swepub:lu)extLU-05
(author)
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Mokoroa, O.Biodonostia Health Research Institute,CIBER Epidemiology and Public Health (CIBERESP)
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Sala, N.Catalan Institute of Oncology
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Sanchez, M. J.University of Granada,CIBER Epidemiology and Public Health (CIBERESP),International Agency for Research on Cancer, World Health Organization
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Huerta, J. M.CIBER Epidemiology and Public Health (CIBERESP),Murcia Regional Health Council
(author)
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Winkvist, Anna,1962Umeå University,Umeå universitet,Gothenburg University,Göteborgs universitet,Institutionen för medicin,Institute of Medicine,Avdelningen för hållbar hälsa,The Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden(Swepub:umu)anwi0332
(author)
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Harlid, Sophia,1978-Umeå University,Umeå universitet,Onkologi(Swepub:lu)mikr-sha
(author)
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Ohlsson, BodilLund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups,Skåne University Hospital(Swepub:lu)kir-boh
(author)
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Sjöberg, KlasLund University,Lunds universitet,Gastroenterologi,Forskargrupper vid Lunds universitet,Gastroenterology,Lund University Research Groups,Skåne University Hospital(Swepub:lu)medf-ksj
(author)
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Schmidt, J. A.University of Oxford
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Wareham, N.University of Cambridge
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Khaw, K. T.University of Cambridge
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Ferrari, P.International Agency for Research on Cancer, World Health Organization
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Rothwell, J. A.Institut Gustave Roussy,International Agency for Research on Cancer, World Health Organization
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Gunter, M.International Agency for Research on Cancer, World Health Organization
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Riboli, E.Imperial College London
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Scalbert, A.International Agency for Research on Cancer, World Health Organization
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Jenab, M.
(author)
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International Agency for Research on Cancer, World Health OrganizationInstitut Universitari d’Investigació en Atenció Primària Jordi Gol
(creator_code:org_t)
Related titles
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In:International Journal of Cancer: Wiley148:3, s. 609-6250020-71361097-0215
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Stepien, M.
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Keski-Rahkonen, ...
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Kiss, A.
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Robinot, N.
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Duarte-Salles, T ...
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Murphy, N.
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show more...
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Perlemuter, G.
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Viallon, V.
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Tjonneland, A.
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Rostgaard-Hansen ...
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Dahm, C. C.
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Overvad, K.
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Boutron-Ruault, ...
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Mancini, F. R.
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Mahannat-Saleh, ...
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Aleksandrova, K.
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Kaaks, R.
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Kühn, Tilman
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Trichopoulou, A.
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Karakatsani, A.
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Panico, S.
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Tumino, R.
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Palli, D.
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Tagliabue, G.
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Naccarati, A.
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Vermeulen, R. C. ...
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Bueno-de-Mesquit ...
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Weiderpass, E.
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Skeie, G.
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Quiros, J. R.
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Ardanaz, Eva
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Mokoroa, O.
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Sala, N.
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Sanchez, M. J.
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Huerta, J. M.
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Winkvist, Anna, ...
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Harlid, Sophia, ...
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Ohlsson, Bodil
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Sjöberg, Klas
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Schmidt, J. A.
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Wareham, N.
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Khaw, K. T.
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Ferrari, P.
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Rothwell, J. A.
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Gunter, M.
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Riboli, E.
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Scalbert, A.
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Jenab, M.
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University of Gothenburg
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Umeå University
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Lund University