Breast Cancer Research and Treatment

, Volume 126, Issue 2, pp 521–527

The CYP17A1 −34T > C polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers

  • Bella Kaufman
  • Yael Laitman
  • Elad Ziv
  • Ute Hamann
  • Diana Torres
  • Ephrat Levy Lahad
  • Rachel Beeri
  • Paul Renbaum
  • Anna Jakubowska
  • Jan Lubinski
  • Tomasz Huzarski
  • Aleksandra Tołoczko-Grabarek
  • Katarzyna Jaworska
  • Katarzyna Durda
  • Amanda B. Sprudle
  • Georgia Chenevix-Trench
  • Jacques Simard
  • Douglas F. Easton
  • Antoniou Antonis
  • Csilla Szabo
  • Eitan Friedman
Epidemiology

Abstract

Exposure to estrogen has a major effect on breast cancer risk. A polymorphism (−34 T > C; rs743572) in the cytochrome P450c17alpha gene (CYP17A1) encoding an enzyme which controls estrogen levels was reportedly associated with breast cancer risk in average risk populations. The effect of this polymorphism on breast or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers has not been thoroughly investigated. With this aim, 2,221 BRCA1 and BRCA2 mutation carriers (1,313 with breast cancer, 279 with ovarian cancer, and 695 asymptomatic carriers), with either BRCA1 (n = 1693) or BRCA2 (n = 528) germline mutations from seven centers were genotyped for the −34 T > C CYP17 polymorphism. Genotyping was accomplished using Taqman allelic discrimination, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) or PCR-based restriction-fragment length polymorphism analysis, and limited sequencing. Data were analyzed using Cox proportional hazards models. The hazard ratios (HRs) for breast cancer was 1.02 (95% CI 0.89–1.17, p = 0.74) and 1.10 (95% CI 0.72–1.67, p = 0.66) for BRCA1 and BRCA2 mutation carriers, respectively. The HRs for ovarian cancer were 1.17 (0.94–1.46, p = 0.17) and 0.91 (0.31–2.67, p = 0.86) for BRCA1 and BRCA2 mutation carriers, respectively. Results remained unaltered when the Israeli cohort (primarily Ashkenazim) was evaluated separately. In conclusion, there was no overall evidence for an association of the −34 T > C CYP17 polymorphism with either breast or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers.

Keywords

BRCA01/BRCA2 mutations Breast cancer risk CYP17 Penetrance modifier Ovarian cancer risk 

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Bella Kaufman
    • 1
    • 3
  • Yael Laitman
    • 2
  • Elad Ziv
    • 4
  • Ute Hamann
    • 5
  • Diana Torres
    • 5
    • 6
  • Ephrat Levy Lahad
    • 7
  • Rachel Beeri
    • 7
  • Paul Renbaum
    • 7
  • Anna Jakubowska
    • 8
  • Jan Lubinski
    • 8
  • Tomasz Huzarski
    • 8
  • Aleksandra Tołoczko-Grabarek
    • 8
  • Katarzyna Jaworska
    • 8
  • Katarzyna Durda
    • 8
  • Amanda B. Sprudle
    • 9
  • Georgia Chenevix-Trench
    • 10
  • Jacques Simard
    • 11
    • 12
    • 13
  • Douglas F. Easton
    • 14
  • Antoniou Antonis
    • 14
  • Csilla Szabo
    • 15
  • Eitan Friedman
    • 2
    • 3
  1. 1.Institute of OncologyChaim Sheba Medical CenterTel-HashomerIsrael
  2. 2.The Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human GeneticsChaim Sheba Medical CenterTel-HashomerIsrael
  3. 3.The Sackler School of MedicineTel Aviv UniversityTel AvivIsrael
  4. 4.Department of Medicine, Comprehensive Cancer CenterUniversity of California San FranciscoSan FranciscoUSA
  5. 5.Molecular Genetics of Breast Cancer (B072)Deutsches Krebsforschungszentrum (DKFZ)HeidlebergGermany
  6. 6.Faculty of Medicine, Human Genetics InstitutePontificia Universidad JaverianaBogotáColombia
  7. 7.The Genetics InstituteSharre Zedek Medical CenterJerusalemIsrael
  8. 8.Department of Genetics and Pathology, International Hereditary Cancer Centre (IHCC)Pomeranian Medical UniversitySzczecinPoland
  9. 9.Genetics and Population Health DivisionQueensland Institute of Medical ResearchBrisbaneAustralia
  10. 10.The Queensland Institute of Medical ResearchRoyal Brisbane HospitalHerstonAustralia
  11. 11.Chaire de recherche du Canada en OncogénétiqueOttawaCanada
  12. 12.Faculté de médecineUniversité LavalQuebecCanada
  13. 13.Directeur, Axe endocrinologie et génomique Centre de recherche du CHUQ/CHULQuebecCanada
  14. 14.Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary CareUniversity of CambridgeCambridgeUK
  15. 15.Mayo Clinic College of MedicineRochesterUSA

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