Cancer risk in Jewish BRCA1 and BRCA2 mutation carriers: Effects of oral contraceptive use and parental origin of mutation

  • Shiri Bernholtz
  • Yael Laitman
  • Bella Kaufman
  • Shani Paluch Shimon
  • Eitan FriedmanEmail author


BRCA1 and BRCA2 germline mutations substantially increase breast and ovarian cancer risk, yet penetrance is incomplete. The effects of oral contraceptives (OC) on breast cancer risk in mutation carriers are unclear, and the putative effect of parental origin of mutation on cancer risk has not been reported. Data on OC use and parental origin of the mutation were obtained at counseling from 888 BRCA1 (n = 638) or BRCA2 (n = 250) Jewish Israeli mutation carriers who were counseled and genotyped in a single medical center. Overall, 403 (45.4%) of participants had breast cancer (age at diagnosis 49.65 ± 12.2 years), 112 (12.6%) ovarian cancer (age at diagnosis 56.8 ± 10.8 years) and the rest (n = 373−42%) were asymptomatic carriers (age at counseling 40.7 ± 10.6 years). Of study participants, 472 (53.15%) ever used OC, and 298 used OC for at least 5 years. In 129 the mutation originated on the paternal side as judged by direct testing or obligate carriership and in 460 the mutation was maternally inherited. Multivariate logistic regression analysis, and stratifying for birth year, age at menarche, breast feeding, and number of births, showed that ever use of OC (Hazards Ratio-HR = 1.84 95% CI 1.465–2.314, P = 0.001) and paternal compared with maternal origin of mutation (OR = 1.55 95% CI 1.14–2.12, P = 0.006) were significantly associated with breast cancer and an earlier age at breast cancer diagnosis. The authors conclude that OC use and paternal origin of mutation affect breast cancer penetrance in Jewish BRCA1 and BRCA2 mutation carriers.


Breast cancer BRCA1/BRCA2 germline mutations OC use Parental origin of mutation 



This study was performed in partial fulfillment of the requirements for graduation of Shiri Bernholtz, from Ort Braude, Karmiel, Israel. This study was sponsored by a grant from the Israel cancer association to the Israeli inherited breast cancer consortium.


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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Shiri Bernholtz
    • 1
  • Yael Laitman
    • 1
  • Bella Kaufman
    • 2
    • 3
  • Shani Paluch Shimon
    • 2
  • Eitan Friedman
    • 1
    • 3
    Email author
  1. 1.Susanne-Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of GeneticsChaim Sheba Medical CenterTel-HashomerIsrael
  2. 2.Institute of OncologyChaim Sheba Medical CenterTel-HashomerIsrael
  3. 3.The Sackler School of MedicineTel-Aviv UniversityRamat AvivIsrael

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