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@ARTICLE{Mukama:275466,
      author       = {T. Mukama$^*$ and B. Srour and T. Johnson$^*$ and V.
                      Katzke$^*$ and R. Kaaks$^*$},
      title        = {{IGF}-1 and risk of morbidity and mortality from cancer,
                      cardiovascular diseases, and all-causes in {EPIC} -
                      {H}eidelberg.},
      journal      = {The journal of clinical endocrinology $\&$ metabolism},
      volume       = {108},
      number       = {10},
      issn         = {0368-1610},
      address      = {Oxford},
      publisher    = {Oxford University Press},
      reportid     = {DKFZ-2023-00776},
      pages        = {e1092-e1105},
      year         = {2023},
      note         = {#EA:C020#LA:C020# / 2023 Sep 18;108(10):e1092-e1105},
      abstract     = {The functional status of organs involved in IGF-1
                      signalling pathways such as the liver influence circulating
                      levels of IGF-1 and hence its relationship with risk of
                      chronic diseases and mortality, yet has received limited
                      attention.To examine the relationship between IGF-1 and risk
                      of morbidity and mortality from cancer, cardiovascular
                      diseases and all-causes, accounting for liver
                      function.Case-cohort design nested within EPIC-Heidelberg.
                      IGF-1 was measured in 7,461 stored serum samples collected
                      from 1994 to 1998. Median follow-up for incident mortality
                      events: 17.5 years.General community.The case-cohort
                      included a subcohort of 1,810 men and 1,890 women, in
                      addition to 1668 incident cases of cancer (623 breast, 577
                      prostate, 202 lung and 268 colorectal cancers), and 1428
                      cases of CVD (707 MIs and 723 strokes) and 2441 cases of
                      death.Higher IGF-1 levels showed direct associations with
                      risks of breast (1.25 $95\%$ CI: [1.06-1.47]) and prostate
                      (1.31 [1.09-1.57]) cancers. Restricted cubic splines plots
                      and models including IGF-1 as quintiles revealed a U-shaped
                      relationship between the biomarker and mortality. Both
                      participants with lowest and highest levels of IGF-1
                      experienced higher hazards of mortality from cancer,
                      cardiovascular diseases and all-causes. The U-shaped form of
                      the relationship persisted but was attenuated in analyses
                      including only participants without any indications of liver
                      dysfunction.This large population-based prospective study
                      showed that both individuals with lowest and highest levels
                      of circulating IGF-1 were at increased risk of deaths from
                      cancer, cardiovascular and all-causes. For individuals with
                      low IGF-1, the excess risks of death were more pronounced
                      among individuals with liver cancer and cirrhosis but were
                      also present among individuals without elevated liver
                      enzymes.},
      keywords     = {IGF-1 (Other) / cancer (Other) / cardiovascular diseases
                      (Other) / liver enzymes (Other) / liver function (Other) /
                      mortality (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:37066827},
      doi          = {10.1210/clinem/dgad212},
      url          = {https://inrepo02.dkfz.de/record/275466},
}