RT Journal Article
T1 Prediagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma.
A1 Stepien, Magdalena
A1 Lopez-Nogueroles, Marina
A1 Lahoz, Agustin
A1 Kühn, Tilman
A1 Perlemuter, Gabriel
A1 Voican, Cosmin
A1 Ciocan, Dragos
A1 Boutron-Ruault, Marie-Christine
A1 Jansen, Eugene
A1 Viallon, Vivian
A1 Leitzmann, Michael
A1 Tjønneland, Anne
A1 Severi, Gianluca
A1 Mancini, Francesca Romana
A1 Dong, Catherine
A1 Kaaks, Rudolf
A1 Fortner, Renee Turzanski
A1 Bergmann, Manuela M
A1 Boeing, Heiner
A1 Trichopoulou, Antonia
A1 Karakatsani, Anna
A1 Peppa, Eleni
A1 Palli, Domenico
A1 Krogh, Vittorio
A1 Tumino, Rosario
A1 Sacerdote, Carlotta
A1 Panico, Salvatore
A1 Bueno-de-Mesquita, H Bas
A1 Skeie, Guri
A1 Merino, Susana
A1 Ros, Raul Zamora
A1 Sanchez-Perez, Maria-Jose
A1 Amiano, Pilar
A1 Huerta, Jose Mª
A1 Barricarte, Aurelio
A1 Sjöberg, Klas
A1 Ohlsson, Bodil
A1 Nyström, Hanna
A1 Werner, Marten
A1 Perez-Cornago, Aurora
A1 Schmidt, Julie A
A1 Freisling, Heinz
A1 Scalbert, Augustin
A1 Weiderpass, Elisabete
A1 Christakoudi, Sofia
A1 Gunter, Marc J
A1 Jenab, Mazda
K1 bile acid metabolism
K1 biomarkers
K1 cancer prevention
K1 hepatocellular carcinoma
K1 obesity
AB Bile acids (BAs) 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/unconjugated) in prediagnostic 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% confidence intervals [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. Increase in BA concentration is accompanied by a shift in BA profile toward 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.
PB John Wiley & Sons, Inc.
YR 2022
FD 2022-11-29
LK http://hdl.handle.net/10668/22051
UL http://hdl.handle.net/10668/22051
LA en
NO Stepien M, Lopez-Nogueroles M, Lahoz A, Kühn T, Perlemuter G, Voican C, et al.  Prediagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma. Int J Cancer. 2022 Apr 15;150(8):1255-1268.
NO This work was supported in part by the French National Cancer Institute (L'Institut National du Cancer; INCa; grant numbers 2009-139 and 2014-1-RT-02-CIRC-1; PI: M. Jenab) and by internal funds of the IARC. The coordination of EPIC is financially supported by the International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS)—Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra and the Catalan Institute of Oncology—ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom). The funding sources had no influence on the design of the study; the collection, analysis and interpretation of data; the writing of the report; or the decision to submit the article for publication.
DS RISalud
RD Apr 7, 2025