@article{3034052,
    title = "Prediagnostic alterations in circulating bile acid profiles in the
development of hepatocellular carcinoma",
    author = "Stepien, Magdalena and Lopez-Nogueroles, Marina and Lahoz, Agustin and and Kuehn, Tilman and Perlemuter, Gabriel and Voican, Cosmin and Ciocan, and Dragos and Boutron-Ruault, Marie-Christine and Jansen, Eugene and and Viallon, Vivian and Leitzmann, Michael and Tjonneland, Anne and Severi, and Gianluca and Mancini, Francesca Romana and Dong, Catherine and Kaaks, and Rudolf and Fortner, Renee Turzanski and Bergmann, Manuela M. and Boeing, and Heiner and Trichopoulou, Antonia and Karakatsani, Anna and Peppa, Eleni and and Palli, Domenico and Krogh, Vittorio and Tumino, Rosario and and Sacerdote, Carlotta and Panico, Salvatore and Bueno-de-Mesquita, H. Bas and and Skeie, Guri and Merino, Susana and Ros, Raul Zamora and Sanchez, and Maria Jose and Amiano, Pilar and Huerta, Jose Ma and Barricarte, Aurelio and and Sjoeberg, Klas and Ohlsson, Bodil and Nystroem, Hanna and Werner, and Marten and Perez-Cornago, Aurora and Schmidt, Julie A. and Freisling, and Heinz and Scalbert, Augustin and Weiderpass, Elisabete and Christakoudi, and Sofia and Gunter, Marc J. and Jenab, Mazda",
    journal = "International Journal  of Cancer",
    year = "2022",
    volume = "150",
    number = "8",
    pages = "1255-1268",
    publisher = "Wiley",
    issn = "0020-7136",
    doi = "10.1002/ijc.33885",
    keywords = "bile acid metabolism; biomarkers; cancer prevention; hepatocellular
carcinoma; obesity",
    abstract = "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."
}