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@ARTICLE{Grafetsttter:143745,
      author       = {M. Grafetstätter$^*$ and A. Hüsing$^*$ and S. González
                      Maldonado$^*$ and D. Sookthai$^*$ and T. S. Johnson$^*$ and
                      L. Pletsch-Borba$^*$ and V. Katzke$^*$ and M.
                      Hoffmeister$^*$ and P. Bugert$^*$ and R. Kaaks$^*$ and T.
                      Kuehn$^*$},
      title        = {{P}lasma {F}ibrinogen and s{P}-{S}electin are associated
                      with the risk of lung cancer in a prospective study.},
      journal      = {Cancer epidemiology, biomarkers $\&$ prevention},
      volume       = {28},
      number       = {7},
      issn         = {1538-7755},
      address      = {Philadelphia, Pa.},
      publisher    = {AACR},
      reportid     = {DKFZ-2019-01314},
      pages        = {1221-1227},
      year         = {2019},
      abstract     = {While enhanced platelet activation and a procoagulant state
                      may drive lung cancer progression and metastases, less is
                      known about their role in earlier phases of cancer
                      development. Thus, we evaluated whether pre-diagnostic
                      biomarkers of platelet activation and coagulation are
                      related to the risk of lung cancer in the prospective
                      EPIC-Heidelberg Study using a case-cohort design.Levels of
                      fibrinogen, soluble glycoprotein (sGP) IIb/IIIa, soluble
                      P-selectin (sP-selectin), soluble thrombomodulin (sTM), and
                      thrombopoietin (TPO) were measured in baseline plasma
                      samples of a random subcohort (n=2,480) and incident cases
                      of lung cancer (n=190). Multivariable-adjusted Cox
                      proportional hazards regression analyses were used to obtain
                      Hazard Ratios (HRs) of lung cancer across quartiles of
                      biomarker levels.Fibrinogen (HR highest vs. lowest quartile:
                      1.91 [95 $\%$ confidence interval: 1.09, 3.34]) and
                      sP-Selectin (HR: 2.51 [1.39, 4.52]) were significantly
                      associated with lung cancer risk in multivariable adjusted
                      Cox regression models. Adding both biomarkers to the
                      established PLCOm2012 algorithm, which alone showed a
                      C-statistic of 0.788, led to a slight increment in lung
                      cancer risk prediction, with a C-statistic of 0.814.Our
                      findings indicate that enhanced platelet activation and a
                      pro-coagulative state contribute to lung carcinogenesis.The
                      present prospective study supports the hypothesis of
                      increased coagulation being a possible driver of lung
                      carcinogenesis, as strong positive associations were found
                      between two procoagulative markers, sP-Selectin and
                      fibrinogen, with lung cancer risk. Both biomarkers could
                      improve lung cancer risk prediction, but external validation
                      of the results is needed.},
      cin          = {C020 / C070},
      ddc          = {610},
      cid          = {I:(DE-He78)C020-20160331 / I:(DE-He78)C070-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31015200},
      doi          = {10.1158/1055-9965.EPI-18-1285},
      url          = {https://inrepo02.dkfz.de/record/143745},
}