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Integrin β3 Leu33Pro polymorphism increases BRCA1-associated ovarian cancer risk
  1. Anna Jakubowska1,
  2. Jacek Gronwald1,
  3. Janusz Menkiszak2,
  4. Bohdan Górski1,
  5. Tomasz Huzarski1,
  6. Tomasz Byrski1,
  7. Lutz Edler4,
  8. Jan Lubiński1,
  9. Rodney J Scott5,
  10. Ute Hamann3
  1. 1Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, ul Polabska, Poland
  2. 2Department of Surgical Gynecology and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, ul Powstancow Wlkp, Szczecin, Poland
  3. 3Division of Molecular Genome Analysis, Molecular Genetics of Breast Cancer, German Cancer Research Center, Heidelberg, Germany
  4. 4Central Unit Biostatistics, German Cancer Research Center, Heidelberg, Germany
  5. 5Discipline of Medical Genetics, School of Biomedical Sciences, University of Newcastle, and the Hunter Medical Research Institute, New Lambton, New South Wales, Australia
  1. Correspondence to:
 Prof U Hamann
 German Cancer Research Center, Division of Molecular Genome Analysis, Molecular Genetics of Breast Cancer, B055, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany; u.hamann{at}dkfz-heidelberg.de

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 analyse the role of this functional polymorphism in modifying BRCA1-associated ovarian and breast cancer risks, a case–control study was performed 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 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. The 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.

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Footnotes

  • Funding: This work was supported by the Deutsches Krebsforschungszentrum, Heidelberg. AJ is a guest researcher from the Pomeranian Medical University, Szczecin, Poland, supported by a fellowship from the DKFZ. AJ and JG were supported by a Yamagiwa-Yoshida Memorial UICC International Cancer Study Grant.

  • Competing interests: None declared.

  • Published Online First 12 January 2007

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