1. ¹Institute of Medical Genetics, Shaare Zedek Medical Center, Hebrew University Medical School, Jerusalem, 91031, Israel
2. ²Oncogenetics Unit, Chaim Sheba Medical Center, Tel-Hashomer 53621; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel

Correspondence: Professor E Levy-Lahad, E-mail: lahad@szmc.org.il

Received 2 October 2006; Revised 16 November 2006; Accepted 17 November 2006.

Abstract

BRCA1 and BRCA2 mutations increase breast and ovarian cancer risks substantially enough to warrant risk reduction surgery, despite variable risk estimates. Underlying this variability are methodological issues, and also complex genetic and nongenetic effects. Although many modifying factors are unidentified, known factors can already be incorporated in individualised risk prediction.