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Prediagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma

Stepien, Magdalena ; Lopez-Nogueroles, Marina ; Lahoz, Agustin ; Kühn, Tilman ; Perlemuter, Gabriel ; Voican, Cosmin ; Ciocan, Dragos ; Boutron-Ruault, Marie Christine ; Jansen, Eugene and Viallon, Vivian , et al. (2022) In International Journal of Cancer 150(8). p.1255-1268
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
bile acid metabolism, biomarkers, cancer prevention, hepatocellular carcinoma, obesity
in
International Journal of Cancer
volume
150
issue
8
pages
14 pages
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:34843121
  • scopus:85122737009
ISSN
0020-7136
DOI
10.1002/ijc.33885
language
English
LU publication?
yes
id
807b160f-c7f7-4b5b-8312-daed6102d9f8
date added to LUP
2022-03-07 14:34:35
date last changed
2022-06-22 03:49:00
@article{807b160f-c7f7-4b5b-8312-daed6102d9f8,
  abstract     = {{<p>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 (OR<sub>doubling</sub> = 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.</p>}},
  author       = {{Stepien, Magdalena and Lopez-Nogueroles, Marina and Lahoz, Agustin and Kühn, Tilman and Perlemuter, Gabriel and Voican, Cosmin and Ciocan, Dragos and Boutron-Ruault, Marie Christine and Jansen, Eugene and Viallon, Vivian and Leitzmann, Michael and Tjønneland, Anne and Severi, Gianluca and Mancini, Francesca Romana and Dong, Catherine and Kaaks, Rudolf and Fortner, Renee Turzanski and Bergmann, Manuela M. and Boeing, Heiner and Trichopoulou, Antonia and Karakatsani, Anna and Peppa, Eleni and Palli, Domenico and Krogh, Vittorio and Tumino, Rosario and Sacerdote, Carlotta and Panico, Salvatore and Bueno-de-Mesquita, H. Bas and Skeie, Guri and Merino, Susana and Ros, Raul Zamora and Sánchez, Maria Jose and Amiano, Pilar and Huerta, Jose Mª and Barricarte, Aurelio and Sjöberg, Klas and Ohlsson, Bodil and Nyström, Hanna and Werner, Marten and Perez-Cornago, Aurora and Schmidt, Julie A. and Freisling, Heinz and Scalbert, Augustin and Weiderpass, Elisabete and Christakoudi, Sofia and Gunter, Marc J. and Jenab, Mazda}},
  issn         = {{0020-7136}},
  keywords     = {{bile acid metabolism; biomarkers; cancer prevention; hepatocellular carcinoma; obesity}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{1255--1268}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{International Journal of Cancer}},
  title        = {{Prediagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma}},
  url          = {{http://dx.doi.org/10.1002/ijc.33885}},
  doi          = {{10.1002/ijc.33885}},
  volume       = {{150}},
  year         = {{2022}},
}