Reproductive and hormonal factors, and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers: Results from the International BRCA1/2 carrier cohort study

Antonis C. Antoniou, Matti Rookus, Nadine Andrieu, Richard Brohet, Jenny Chang-Claude, Susan Peock, Margaret Cook, D. Gareth Evans, Rosalind Eeles, Catherine Nogues Embrace, Laurence Faivre, Paul Gesta, Genepso Flora E. Van Leeuwen, Margreet G.E.M. Ausems, Ana Osorio Geo-Hebon, Trinidad Caldes, Jacques Simard, Jan Lubinski, Anne Marie Gerdes, Edith OlahChristine Fürhauser, Hakan Olsson, Brita Arver, Paolo Radice, Douglas F. Easton, David E. Goldgar

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Abstract

Background: Several reproductive and hormonal factors are known to be associated with ovarian cancer risk in the general population, including parity and oral contraceptive (OC) use. However, their effect on ovarian cancer risk for BRCA1 and BRCA2 mutation carriers has only been investigated in a small number of studies. Methods: We used data on 2,281 BRCA1 carriers and 1,038 BRCA2 carriers from the International BRCA1/2 Carrier Cohort Study to evaluate the effect of reproductive and hormonal factors on ovarian cancer risk for mutation carriers. Data were analyzed within a weighted Cox proportional hazards framework. Results: There were no significant differences in the risk of ovarian cancer between parous and nulliparous carriers. For parous BRCA1 mutation carriers, the risk of ovarian cancer was reduced with each additional full-term pregnancy (P trend = 0.002). BRCA1 carriers who had ever used OC were at a significantly reduced risk of developing ovarian cancer (hazard ratio, 0.52; 95% confidence intervals, 0.37-0.73; P = 0.0002) and increasing duration of OC use was associated with a reduced ovarian cancer risk (P trend = 0.0004). The protective effect of OC use for BRCA1 mutation carriers seemed to be greater among more recent users. Tubal ligation was associated with a reduced risk of ovarian cancer for BRCA1 carriers (hazard ratio, 0.42; 95% confidence intervals, 0.22-0.80; P = 0.008). The number of ovarian cancer cases in BRCA2 mutation carriers was too small to draw definitive conclusions. Conclusions: The results provide further confirmation that OC use, number of full-term pregnancies, and tubal ligation are associated with ovarian cancer risk in BRCA1 carriers to a similar relative extent as in the general population.

Original languageEnglish
Pages (from-to)601-610
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Volume18
Issue number2
DOIs
Publication statusPublished - Feb 1 2009

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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    Antoniou, A. C., Rookus, M., Andrieu, N., Brohet, R., Chang-Claude, J., Peock, S., Cook, M., Evans, D. G., Eeles, R., Embrace, C. N., Faivre, L., Gesta, P., Van Leeuwen, G. F. E., Ausems, M. G. E. M., Geo-Hebon, A. O., Caldes, T., Simard, J., Lubinski, J., Gerdes, A. M., ... Goldgar, D. E. (2009). Reproductive and hormonal factors, and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers: Results from the International BRCA1/2 carrier cohort study. Cancer Epidemiology Biomarkers and Prevention, 18(2), 601-610. https://doi.org/10.1158/1055-9965.EPI-08-0546