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