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  3. Pre-diagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma.

Pre-diagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma.

Fecha de publicación: Fecha Ahead of Print:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

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

Grupos

Abstract

Bile 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 (OR(doubling)  = 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.

© 2021 UICC.

Datos de la publicación

ISSN/ISSNe:
0020-7136, 1097-0215

INTERNATIONAL JOURNAL OF CANCER  WILEY

Tipo:
Article
Páginas:
1255-1268
PubMed:
34843121
Factor de Impacto:
2,056 SCImago ℠
Cuartil:
Q1 SCImago ℠

Citas Recibidas en Web of Science: 62

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Keywords

  • bile acid metabolism; biomarkers; cancer prevention; hepatocellular carcinoma; obesity

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