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@ARTICLE{Stepien:177704,
      author       = {M. Stepien and M. Lopez-Nogueroles and A. Lahoz and T.
                      Kühn$^*$ and G. Perlemuter and C. Voican and D. Ciocan and
                      M.-C. Boutron-Ruault and E. Jansen and V. Viallon and M.
                      Leitzmann and A. Tjønneland and G. Severi and F. R. Mancini
                      and C. Dong and R. Kaaks$^*$ and R. T. Fortner$^*$ and M. M.
                      Bergmann and H. Boeing and A. Trichopoulou and A.
                      Karakatsani and E. Peppa and D. Palli and V. Krogh and R.
                      Tumino and C. Sacerdote and S. Panico and H. B.
                      Bueno-de-Mesquita and G. Skeie and S. Merino and R. Z. Ros
                      and M. J. Sánchez and P. Amiano and J. M. Huerta and A.
                      Barricarte and K. Sjöberg and B. Ohlsson and H. Nyström
                      and M. Werner and A. Perez-Cornago and J. A. Schmidt and H.
                      Freisling and A. Scalbert and E. Weiderpass and S.
                      Christakoudi and M. J. Gunter and M. Jenab},
      title        = {{P}re-diagnostic alterations in circulating bile acid
                      profiles in the development of hepatocellular carcinoma.},
      journal      = {International journal of cancer},
      volume       = {150},
      number       = {8},
      issn         = {0020-7136},
      address      = {Bognor Regis},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2021-02752},
      pages        = {1255-1268},
      year         = {2022},
      note         = {Volume150, Issue8, 15 April 2022, Pages 1255-1268},
      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 (ORdoubling  =
                      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.},
      keywords     = {bile acid metabolism (Other) / biomarkers (Other) / cancer
                      prevention (Other) / hepatocellular carcinoma (Other) /
                      obesity (Other)},
      cin          = {C020},
      ddc          = {610},
      cid          = {I:(DE-He78)C020-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34843121},
      doi          = {10.1002/ijc.33885},
      url          = {https://inrepo02.dkfz.de/record/177704},
}