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000143745 1001_ $$0P:(DE-HGF)0$$aGrafetstätter, Mirja$$b0$$eFirst author
000143745 245__ $$aPlasma Fibrinogen and sP-Selectin are associated with the risk of lung cancer in a prospective study.
000143745 260__ $$aPhiladelphia, Pa.$$bAACR$$c2019
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000143745 520__ $$aWhile enhanced platelet activation and a procoagulant state may drive lung cancer progression and metastases, less is known about their role in earlier phases of cancer development. Thus, we evaluated whether pre-diagnostic biomarkers of platelet activation and coagulation are related to the risk of lung cancer in the prospective EPIC-Heidelberg Study using a case-cohort design.Levels of fibrinogen, soluble glycoprotein (sGP) IIb/IIIa, soluble P-selectin (sP-selectin), soluble thrombomodulin (sTM), and thrombopoietin (TPO) were measured in baseline plasma samples of a random subcohort (n=2,480) and incident cases of lung cancer (n=190). Multivariable-adjusted Cox proportional hazards regression analyses were used to obtain Hazard Ratios (HRs) of lung cancer across quartiles of biomarker levels.Fibrinogen (HR highest vs. lowest quartile: 1.91 [95 % confidence interval: 1.09, 3.34]) and sP-Selectin (HR: 2.51 [1.39, 4.52]) were significantly associated with lung cancer risk in multivariable adjusted Cox regression models. Adding both biomarkers to the established PLCOm2012 algorithm, which alone showed a C-statistic of 0.788, led to a slight increment in lung cancer risk prediction, with a C-statistic of 0.814.Our findings indicate that enhanced platelet activation and a pro-coagulative state contribute to lung carcinogenesis.The present prospective study supports the hypothesis of increased coagulation being a possible driver of lung carcinogenesis, as strong positive associations were found between two procoagulative markers, sP-Selectin and fibrinogen, with lung cancer risk. Both biomarkers could improve lung cancer risk prediction, but external validation of the results is needed.
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000143745 7001_ $$0P:(DE-He78)6519c85d61a3def7974665471b8a4f74$$aHüsing, Anika$$b1$$udkfz
000143745 7001_ $$0P:(DE-HGF)0$$aGonzález Maldonado, Sandra$$b2
000143745 7001_ $$0P:(DE-He78)fd4ffe2a3f08e0158b82400acd6716be$$aSookthai, Disorn$$b3$$udkfz
000143745 7001_ $$0P:(DE-He78)79ab945544e5bc017a2317b6146ed3aa$$aJohnson, Theron S$$b4$$udkfz
000143745 7001_ $$0P:(DE-HGF)0$$aPletsch-Borba, Laura$$b5
000143745 7001_ $$0P:(DE-He78)fb68a9386399d72d84f7f34cfc6048b4$$aKatzke, Verena$$b6$$udkfz
000143745 7001_ $$0P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aHoffmeister, Michael$$b7$$udkfz
000143745 7001_ $$0P:(DE-HGF)0$$aBugert, Peter$$b8
000143745 7001_ $$0P:(DE-He78)4b2dc91c9d1ac33a1c0e0777d0c1697a$$aKaaks, Rudolf$$b9$$udkfz
000143745 7001_ $$0P:(DE-HGF)0$$aKuehn, Tilman$$b10$$eLast author
000143745 773__ $$0PERI:(DE-600)2036781-8$$a10.1158/1055-9965.EPI-18-1285$$gp. cebp.1285.2018 -$$n7$$p1221-1227$$tCancer epidemiology, biomarkers & prevention$$v28$$x1538-7755$$y2019
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