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000177704 041__ $$aEnglish
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000177704 1001_ $$aStepien, Magdalena$$b0
000177704 245__ $$aPre-diagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma.
000177704 260__ $$aBognor Regis$$bWiley-Liss$$c2022
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000177704 500__ $$aVolume150, Issue8, 15 April 2022, Pages 1255-1268
000177704 520__ $$aBile acids (BA) play different roles in cancer development. Some are carcinogenic and BA signaling is also involved in various metabolic, inflammatory, and immune-related processes. The liver is the primary site of BA synthesis. Liver dysfunction and microbiome compositional changes, such as during hepatocellular carcinoma (HCC) development, may modulate BA metabolism increasing concentration of carcinogenic BAs. Observations from prospective cohorts are sparse. We conducted a study (233 HCC case-control pairs) nested within a large observational prospective cohort with blood samples taken at recruitment when healthy with follow-up over time for later cancer development. A targeted metabolomics method was used to quantify 17 BAs (primary/secondary/tertiary; conjugated/un-conjugated) in pre-diagnostic plasma. Odd ratios (OR) for HCC risk associations were calculated by multivariable conditional logistic regression models. Positive HCC risk associations were observed for the molar sum of all BAs (ORdoubling  = 2.30, 95%CI = 1.76-3.00) and choline- and taurine-conjugated BAs. Relative concentrations of BAs showed positive HCC risk associations for glycoholic acid and most taurine-conjugated BAs. We observe an association between increased HCC risk and higher levels of major circulating BAs, from several years prior to tumor diagnosis and after multivariable adjustment for confounders and liver functionality. Increased in BA concentration is accompanied by a shift in BA profile towards higher proportions of taurine-conjugated BAs, indicating early alterations of BA metabolism with HCC development. Future studies are needed to assess BA profiles for improved stratification of patients at high HCC risk and to determine whether supplementation with certain BAs may ameliorate liver dysfunction. This article is protected by copyright. All rights reserved.
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000177704 650_7 $$2Other$$abile acid metabolism
000177704 650_7 $$2Other$$abiomarkers
000177704 650_7 $$2Other$$acancer prevention
000177704 650_7 $$2Other$$ahepatocellular carcinoma
000177704 650_7 $$2Other$$aobesity
000177704 7001_ $$aLopez-Nogueroles, Marina$$b1
000177704 7001_ $$aLahoz, Agustin$$b2
000177704 7001_ $$0P:(DE-He78)0907a10ba1dc8f53f04907f54f6fdcfe$$aKühn, Tilman$$b3
000177704 7001_ $$aPerlemuter, Gabriel$$b4
000177704 7001_ $$aVoican, Cosmin$$b5
000177704 7001_ $$aCiocan, Dragos$$b6
000177704 7001_ $$00000-0002-5956-5693$$aBoutron-Ruault, Marie-Christine$$b7
000177704 7001_ $$aJansen, Eugene$$b8
000177704 7001_ $$aViallon, Vivian$$b9
000177704 7001_ $$aLeitzmann, Michael$$b10
000177704 7001_ $$aTjønneland, Anne$$b11
000177704 7001_ $$aSeveri, Gianluca$$b12
000177704 7001_ $$00000-0003-2297-3869$$aMancini, Francesca Romana$$b13
000177704 7001_ $$aDong, Catherine$$b14
000177704 7001_ $$0P:(DE-He78)4b2dc91c9d1ac33a1c0e0777d0c1697a$$aKaaks, Rudolf$$b15$$udkfz
000177704 7001_ $$0P:(DE-He78)74a6af8347ec5cbd4b77e562e10ca1f2$$aFortner, Renee Turzanski$$b16$$udkfz
000177704 7001_ $$aBergmann, Manuela M$$b17
000177704 7001_ $$aBoeing, Heiner$$b18
000177704 7001_ $$aTrichopoulou, Antonia$$b19
000177704 7001_ $$aKarakatsani, Anna$$b20
000177704 7001_ $$aPeppa, Eleni$$b21
000177704 7001_ $$aPalli, Domenico$$b22
000177704 7001_ $$00000-0003-0122-8624$$aKrogh, Vittorio$$b23
000177704 7001_ $$aTumino, Rosario$$b24
000177704 7001_ $$00000-0002-8008-5096$$aSacerdote, Carlotta$$b25
000177704 7001_ $$aPanico, Salvatore$$b26
000177704 7001_ $$aBueno-de-Mesquita, H Bas$$b27
000177704 7001_ $$aSkeie, Guri$$b28
000177704 7001_ $$aMerino, Susana$$b29
000177704 7001_ $$00000-0002-6236-6804$$aRos, Raul Zamora$$b30
000177704 7001_ $$aSánchez, Maria Jose$$b31
000177704 7001_ $$aAmiano, Pilar$$b32
000177704 7001_ $$aHuerta, Jose Mª$$b33
000177704 7001_ $$aBarricarte, Aurelio$$b34
000177704 7001_ $$aSjöberg, Klas$$b35
000177704 7001_ $$aOhlsson, Bodil$$b36
000177704 7001_ $$aNyström, Hanna$$b37
000177704 7001_ $$aWerner, Marten$$b38
000177704 7001_ $$aPerez-Cornago, Aurora$$b39
000177704 7001_ $$00000-0002-7733-8750$$aSchmidt, Julie A$$b40
000177704 7001_ $$00000-0001-8648-4998$$aFreisling, Heinz$$b41
000177704 7001_ $$aScalbert, Augustin$$b42
000177704 7001_ $$00000-0003-2237-0128$$aWeiderpass, Elisabete$$b43
000177704 7001_ $$00000-0001-9219-4436$$aChristakoudi, Sofia$$b44
000177704 7001_ $$aGunter, Marc J$$b45
000177704 7001_ $$00000-0002-0573-1852$$aJenab, Mazda$$b46
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