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@ARTICLE{Katzke:153922,
      author       = {V. Katzke$^*$ and T. Johnson$^*$ and D. Sookthai$^*$ and A.
                      Hüsing$^*$ and T. Kühn$^*$ and R. Kaaks$^*$},
      title        = {{C}irculating liver enzymes and risks of chronic diseases
                      and mortality in the prospective {EPIC}-{H}eidelberg
                      case-cohort study.},
      journal      = {BMJ open},
      volume       = {10},
      number       = {3},
      issn         = {2044-6055},
      address      = {London},
      publisher    = {BMJ Publishing Group},
      reportid     = {DKFZ-2020-00532},
      pages        = {e033532},
      year         = {2020},
      note         = {#EA:C020#LA:C020#},
      abstract     = {Elevated liver enzyme concentrations in blood are
                      indicative of liver diseases and may provide an early signal
                      for being at risk for other chronic diseases. Our study
                      aimed to assess the relationships of alkaline phosphatase
                      (ALP), gamma-glutamyltransferase (GGT), alanine
                      aminotransferase (ALT), aspartate transaminase (AST) and the
                      De Ritis ratio (AST/ALT) with incidence and mortality of
                      cardiovascular diseases (CVD) and the four most common
                      cancers, that is, breast, prostate, colorectal and lung.We
                      analysed a case-cohort sample of the prospective European
                      Prospective Investigation into Cancer and
                      Nutrition-Heidelberg cohort, including cancer (n=1632),
                      cancer mortality (n=761), CVD (n=1070), CVD mortality
                      (n=381) and a random subcohort (n=2739) with an average
                      follow-up duration of 15.6 years. Concentrations of liver
                      enzymes were measured in prediagnostic blood samples and
                      Prentice-weighted Cox regression models were used to
                      estimate HRs with $95\%$ CIs.High ALP levels were associated
                      with increased risk for lung cancer and all-cause mortality
                      (highest vs lowest quartile, multivariable adjusted HR=2.39
                      $(95\%$ CI 1.30 to 4.39), HR=1.31 $(95\%$ CI 1.02 to 1.67)),
                      high AST levels with all-cause mortality (HR=1.45 $(95\%$ CI
                      1.15 to 1.82)), and a high De Ritis ratio with prostate
                      cancer risk, all-cause and cancer mortality (HR=1.61 $(95\%$
                      CI 1.10 to 2.36), HR=1.60 $(95\%$ CI 1.25 to 2.04), HR=1.67
                      $(95\%$ CI 1.26 to 2.23)). Using cut-points for liver enzyme
                      levels above normal, we observed positive associations for
                      all-cause mortality with ALP, GGT and AST, and assigning a
                      combined risk score resulted in positive associations with
                      all-cause and cause-specific mortality.Measurements of serum
                      liver enzymes, as routinely performed in health check-ups,
                      may support the identification of individuals at increased
                      risk for all-cause mortality. Further prospective studies
                      are needed to verify our first results on individual cancers
                      and on a combined risk score.},
      cin          = {C020},
      ddc          = {610},
      cid          = {I:(DE-He78)C020-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32152162},
      doi          = {10.1136/bmjopen-2019-033532},
      url          = {https://inrepo02.dkfz.de/record/153922},
}