title: Integrin beta-3 genetic variants and risk of venous thromboembolism in colorectal cancer patients.
abstract: BACKGROUND
  Integrin β3 is involved in tumor and endothelial cell biology as well as in platelet aggregation. Herein, we evaluated the predictive potential of three germline single nucleotide polymorphisms (SNPs) in the integrin β3 gene (rs3809865, rs5918 and rs4642) to predict the risk of venous thromboembolism (VTE) in colorectal cancer (CRC) patients, which is one of the leading causes of death among cancer patients.
  
  
  METHODS
  112 patients diagnosed with CRC enrolled in the prospective Vienna Cancer and Thrombosis Study (CATS) were assessed with a median follow-up of 46 months. DNA was isolated from venous blood samples and SNPs were analyzed by the PCR-RFLP method.
  
  
  RESULTS
  VTE occurred in 12% (n=13) of all patients. The SNPs rs5918 and rs4642 were not associated with VTE risk. For rs3809565, 23% (n=11) of patients had the A/A genotype, 4% (n=2) had the A/T genotype, but none (0%) had the T/T genotype. In the univariate analysis, patients with the A/A genotype had a significantly higher risk to develop VTE compared to the other polymorphisms (P=0.0005 after Fine and Gray). In the multivariable analysis, the predictive value remained significant.
  
  
  CONCLUSIONS
  This study identified the rs3809865 A/A genotype as an independent risk factor for VTE in CRC patients. Our findings would help identify high risk patients and would be essential for tailored anticoagulant prophylaxis.
authors.affiliation: Department of Internal Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Bianconi
authors.affiliation: Department of Internal Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schuler
authors.affiliation: Department of Internal Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Austria.
authors.forename: Clemens
authors.initials: C
authors.lastname: Pausz
authors.affiliation: Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Austria.
authors.forename: Angelika
authors.initials: A
authors.lastname: Geroldinger
authors.affiliation: Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kaider
authors.affiliation: Norris Cancer Center, University of Southern California, Los Angeles, CA, USA.
authors.forename: Heinz-Josef
authors.initials: HJ
authors.lastname: Lenz
authors.affiliation: Department of Internal Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Austria.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Kornek
authors.affiliation: Department of Internal Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Scheithauer
authors.affiliation: Department of Internal Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Austria.
authors.forename: Christoph C
authors.initials: CC
authors.lastname: Zielinski
authors.affiliation: Department of Internal Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Austria.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Pabinger
authors.affiliation: Department of Internal Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Austria. Electronic address: cihan.ay@meduniwien.ac.at.
authors.forename: Cihan
authors.initials: C
authors.lastname: Ay
authors.affiliation: Department of Internal Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Austria. Electronic address: gerald.prager@meduniwien.ac.at.
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Prager
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D039661:Integrin beta3 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D054556:Venous Thromboembolism / Q000097:blood / Q000235:genetics*
chemical_list: D039661:Integrin beta3
keywords: Anticoagulant prophylaxis; Colorectal cancer; Integrin β3; Single nucleotide polymorphism; Venous thromboembolism risk; rs3809565