Abstract 3700: Prepubertal dietary genistein intake reduces ovarian cancer risk in BRCA+/- mice.

Abstract

Abstract Genistein, a soy-derived isoflavone, is thought to play a key role in the cancer-preventive activity of soy consumption. Germline mutations in BRCA1 and BRCA2 genes are known risk factors for both ovarian and breast cancers. Previously, our lab has discovered that prepubertal dietary exposure to genistein reduced 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary incidence (P = 0.029) and aggressiveness of the tumors (P < 0.001) in the WT mice, and upregulated the expression of BRCA1 in their mammary glands (P = 0.04). In this study, we investigated whether prepubertal dietary exposure to genistein reduces ovarian tumors in heterozygous BRCA+/- mice and their wild type littermates. Mice were fed a control diet AIN93G or 500 ppm genistein-supplemented diet from postnatal day (PND) 15 to PND 30, and thereafter mice received the control AIN93G diet. On PND42, control and genistein mice were primed with medroxyprogesterone acetate and, starting at PND50, administered 7,12-dimethylbenz(a)anthracene (DMBA) once a week for four weeks. Ovarian tissues were harvested at 5 months of age. Histopathology assessment shows that mice developed granulosa cell tumors. Ovarian tumor incidence in control diet fed wildtype mice was 80% and in the BRCA+/- mice 100%. The incidence dropped to 33% in the wildtype and to 50% in the BRCA+/- mice following prepubertal genistein intake. Thus, the exposure to prepubertal genistein in both BRCA+/- and WT mice significantly reduced ovarian tumor incidence, compared with their control diet fed littermates (P=0.001). The mechanisms mediating the protective effect of prepubertal genistein intake on ovarian cancer risk are being investigated. Citation Format: E Carney, L. Hilakivi-Clarke, A. Warri, S. de Assis. Prepubertal dietary genistein intake reduces ovarian cancer risk in BRCA+/- mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3700. doi:10.1158/1538-7445.AM2013-3700