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Integrin ß3 Leu33Pro polymorphism increases BRCA1-associated ovarian cancer risk
  1. Anna Jakubowska (aniaj{at}sci.pam.szczecin.pl)
  1. Pomeranian Medical University, Poland
    1. Jacek Gronwald (jgron{at}uoo.univ.szczecin.pl)
    1. Pomeranian Medical University, Poland
      1. Janusz Menkiszak
      1. Pomeranian Medical University, Poland
        1. Bohdan Górski (gorskib{at}sci.pam.szczecin.pl)
        1. Pomeranian Medical University,, Poland
          1. Tomasz Huzarski
          1. Pomeranian Medical University, Poland
            1. Tomasz Byrski
            1. Pomeranian Medical University, Poland
              1. Lutz Edler
              1. German Cancer Research Center, Germany
                1. Jan Lubinski (lubinski{at}sci.pam.szczecin.pl)
                1. Pomeranian Medical University - International Hereditary Cancer Center, Poland
                  1. Rodney J Scott (rodney.scott{at}newcastle.edu.au)
                  1. University of Newcastle, Australia
                    1. Ute Hamann (u.hamann{at}dkfz-heidelberg.de)
                    1. German Cancer Research Center, Germany

                      Abstract

                      Integrins are heterodimeric transmembrane glycoproteins that function as key adhesion and cell signalling receptors. A functional polymorphism in the integrin β3 subunit encoded by the ITGB3 gene, Leu33Pro has been shown to modify a variety of traits of β3 expressing cells. To analyze the role of this functional polymorphism in modifying BRCA1-associated ovarian and breast cancer risks, we performed a case-control study among Polish BRCA1 mutation carriers including 319 breast cancer cases, 146 ovarian cancer cases and 290 controls unaffected by breast and ovarian cancer, in situ breast cancer or any other kind of cancer. Genotyping analysis was performed using PCR-based restriction fragment length polymorphism analysis. Odds ratios (OR) were calculated using univariate and multivariate logistic regression taking into account a series of confounding variables including the presence of related study subjects that potentially could have biased any association. Our results revealed that the ITGB3_Leu33Pro polymorphism was associated with a 2.5-fold increased risk of ovarian cancer, whereas no association with breast cancer risk was found. Thus, it appears that the ITGB3_Leu33Pro polymorphism may potentially increase the risk of ovarian cancer in Polish women with an inherited BRCA1 mutation.

                      • BRCA1 carriers
                      • Integrin β3 Leu233Pro polymorphism
                      • hereditary breast/ovarian cancer
                      • risk modifier

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