Περίληψη:
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.
Συγγραφείς:
Stepien, Magdalena
Lopez-Nogueroles, Marina
Lahoz, Agustin and
Kuehn, Tilman
Perlemuter, Gabriel
Voican, Cosmin
Ciocan,
Dragos
Boutron-Ruault, Marie-Christine
Jansen, Eugene and
Viallon, Vivian
Leitzmann, Michael
Tjonneland, Anne
Severi,
Gianluca
Mancini, Francesca Romana
Dong, Catherine
Kaaks,
Rudolf
Fortner, Renee Turzanski
Bergmann, Manuela M.
Boeing,
Heiner
Trichopoulou, Antonia
Karakatsani, Anna
Peppa, Eleni
and Palli, Domenico
Krogh, Vittorio
Tumino, Rosario and
Sacerdote, Carlotta
Panico, Salvatore
Bueno-de-Mesquita, H. Bas
and Skeie, Guri
Merino, Susana
Ros, Raul Zamora
Sanchez,
Maria Jose
Amiano, Pilar
Huerta, Jose Ma
Barricarte, Aurelio
and Sjoeberg, Klas
Ohlsson, Bodil
Nystroem, Hanna
Werner,
Marten
Perez-Cornago, Aurora
Schmidt, Julie A.
Freisling,
Heinz
Scalbert, Augustin
Weiderpass, Elisabete
Christakoudi,
Sofia
Gunter, Marc J.
Jenab, Mazda
