Breast Cancer Research and Treatment

, Volume 121, Issue 3, pp 639–649

The Leu33Pro polymorphism in the ITGB3 gene does not modify BRCA1/2-associated breast or ovarian cancer risks: results from a multicenter study among 15,542 BRCA1 and BRCA2 mutation carriers

  • Anna Jakubowska
  • Dominik Rozkrut
  • Antonis Antoniou
  • Ute Hamann
  • Jan Lubinski
Epidemiology

Abstract

Integrins containing the β3 subunit are key players in tumor growth and metastasis. A functional Leu33Pro polymorphism (rs5918) in the β3 subunit of the integrin gene (ITGB3) has previously been suggested to act as a modifier of ovarian cancer risk in Polish BRCA1 mutation carriers. To investigate the association further, we genotyped 9,998 BRCA1 and 5,544 BRCA2 mutation carriers from 34 studies from the Consortium of Investigators of Modifiers of BRCA1/2 for the ITGB3 Leu33Pro polymorphism. Data were analysed within a Cox-proportional hazards framework using a retrospective likelihood approach. There was marginal evidence that the ITGB3 polymorphism was associated with an increased risk of ovarian cancer for BRCA1 mutation carriers (per-allele Hazard Ratio (HR) 1.11, 95% CI 1.00–1.23, p-trend 0.05). However, when the original Polish study was excluded from the analysis, the polymorphism was no longer significantly associated with ovarian cancer risk (HR 1.07, 95% CI 0.96–1.19, p-trend 0.25). There was no evidence of an association with ovarian cancer risk for BRCA2 mutation carriers (HR 1.09, 95% CI 0.89–1.32). The polymorphism was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers. The ITGB3 Leu33Pro polymorphism does not modify breast or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers.

Keywords

ITGB3 Leu33Pro BRCA1 BRCA2 Breast cancer Ovarian cancer 

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Anna Jakubowska
    • 1
  • Dominik Rozkrut
    • 2
  • Antonis Antoniou
    • 3
  • Ute Hamann
    • 4
  • Jan Lubinski
    • 1
  1. 1.IHCC (International Hereditary Cancer Centre), Department of Genetics and PathologyPomeranian Medical UniversitySzczecinPoland
  2. 2.Department of Statistics and Econometrics, School of Economics and ManagementUniversity of SzczecinSzczecinPoland
  3. 3.Cancer Research UK Genetic Epidemiology Unit, Department of Public Health and Primary CareUniversity of CambridgeCambridgeUK
  4. 4.Division of Molecular Genome Analysis, Molecular Genetics of Breast CancerGerman Cancer Research Center (DKFZ)HeidelbergGermany

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