Younger birth cohort correlates with higher breast and ovarian cancer risk in European BRCA1 mutation carriers

Authors


  • Communicated by Dvorah Abeliovich

  • The members of the Austrian Hereditary Breast and Ovarian Cancer Group are: A. Bachmann, K. Matthae, Hospital of Hall/Tyrol; M. Bachner, General Hospital of St. Poelten; C. Baldinger, General Hospital of Wels; M. Baldinger, R. Kusatz, Wels; H. Concin, M. Rohde, General Hospital of Bregenz; W. Doeller, E. Melbinger, General Hospital of Wolfsberg; H.-C. Duba, Women's General Hospital, Linz; E.P. Forsthuber, S. Sussitz, General Hospital of Klagenfurt; A. Haid, A. Lang, A. Taraben, R. Koeberle-Wuehrer, General Hospital of Feldkirch; E. Klug, General Hospital of Oberwart; R. Leikermoser, W. Hochmeir, D. Krichbaumer, Hospital of St. Elisabeth, Linz; C. Schmidhammer, S. Poestlberger, Hospital of the Merciful Sisters, Linz; P. Mayer, B. Mlineritsch, General Hospital of Salzburg; A. Meixner, General Hospital of Freistadt; T. Payrits, Hospital of Wiener Neustadt; F. Peintinger, T. Niernberger, General Hospital of Leoben; E. Petru, P. Steindorfer, P. Konstantiniuk, University of Graz; E. Ropp, Klagenfurt; C. Menzel, S. Glueck, General Hospital of Salzburg; C. Tausch, Linz; C. Smekal-Schindelwig, University of Innsbruck; G. Wahl, General Hospital of Linz; J. Wiegele, Kufstein; and S. Schaefer, S. Berning, Hospital of Kardinal Schwarzenberg, Schwarzach/Pongau (all in Austria).

Abstract

Mutations in the BRCA1 gene result in an elevated risk of breast cancer (BC) and ovarian cancer (OC). However, risk estimates vary depending on the study population and statistical methodology used, and there are indications that the birth cohort and location of the mutation influence cancer risk. We investigated the risks for BC and OC associated with BRCA1 mutations in a young cohort of female mutation carriers who were identified by molecular genetic testing and belonged to a genetically heterogeneous Central European population. The study included 106 healthy and 158 affected carriers identified at an Austrian risk evaluation center. Risk estimation employed the product limit method. The log rank test was used to compare different strata. The risk of developing cancer to age 70 was found to be 85% for BC (95% CI 75–97%) and 53% for OC (95% CI 37–68%). Female mutation carriers born in 1958 or later were subject to a significantly higher risk of BC (P=0.005; 27% vs. 46% to age 40) and OC (P=0.006; 2% vs. 8% to age 40) than those born earlier. Mutations in exon 11 were associated with lower BC risk than mutations in exons 1–10 (P=0.008) and exons 12–24 (P=0.0006). OC risk was not influenced by mutation location (P=0.86). We conclude that female BRCA1 mutation carriers should be counseled about their cohort-dependent cancer risk. Further research into variables that affect cancer risk and are amenable to modification (e.g., lifestyle-related factors) should be considered a priority. Hum Mutat 26(6), 583–589, 2005. © 2005 Wiley-Liss, Inc.

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