Abstract 1605: Time-dependent maternal soybean genistein exposure leads to later-life breast cancer chemoprevention in mice

Abstract

Abstract Breast cancer is the most common type of cancer and the second leading cause of death among women in the United States. Studies have shown that both environmental and genetic factors contribute to breast cancer risk over women's lifespans. Early-life nutritional status has a significant impact on the uterine environment and subsequent fetal development, predisposing the developing fetus to certain diseases such as breast cancer in adult life. During these windows of susceptibility including maternal pre-pregnancy, pregnancy and lactation periods, certain dietary exposure during these critical time periods may change breast cancer risk in an individual’s later life. Alterations of the maternal diet have been shown to induce modifications in the fetal epigenome. Nevertheless, the vulnerability to maternal nutrition status during the critical developmental stage provides an excellent opportunity to re-program epigenetic profiles that may lead to a beneficial outcome such as cancer prevention in the offspring. The bioactive dietary component, genistein (GE) enriched in soybean products, is an important epigenetic modulator that can prevent various cancers including breast cancer. Our study focuses on how maternal dietary soybean GE exposure during the specific time periods may prevent breast cancer in later-life and the potential mechanisms. In this study, we included multiple exposure time points of maternal GE diet (250 mg/kg) including prior-pregnancy (PP-GE), long-term (LT-GE) and short-term (ST-GE) exposures to further determine the efficacy of these strategies on transplacental chemoprevention of breast cancer in the progenies of two spontaneous breast cancer transgenic mouse models. Our pilot study indicates a time-dependent effect of maternal GE exposure on early-life breast cancer development in spontaneous breast cancer mouse models. We also integrated transcriptome and methylome data from mouse breast tumors and identified several candidate genes such as Trp63 and Tprg in response to maternal GE treatment, and considered to play important roles in regulation of development and tumorigenesis. These results suggest that an appropriate exposure window to soybean dietary GE could be a key factor for prevention of human breast cancer and comprehensive mechanisms may be involved in dietary GE-induced in utero breast cancer intervention. Citation Format: Yuanyuan Li, Min Chen, Shizhao Li, Trygve Tollefsbol. Time-dependent maternal soybean genistein exposure leads to later-life breast cancer chemoprevention in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1605.