IsoCross: Cross-species comparison of isoflavone intervention on estrogen sensitivity, metabolism, epigenetics and carcinogenesis

There is an ongoing controversial debate whether phytoestrogenic isoflavones (IF) found for example in soy products have breast cancer preventive activity, or whether exposure to isoflavones may even increase the breast cancer risk.

The aim of the DFG-funded IsoCross initiative is to characterise molecular mechanisms which determine whether the exposure towards specific IF metabolite profiles may be adverse or protective with respect to the risk to develop breast cancer, and to correlate them with levels of IF/E2 metabolites, taking into account the influence of dietary fat consumption and body fatness.

The DKFZ subproject of IsoCross will characterize genome-wide epigentic changes in mammary gland tissue after IF expoure for specific time intervals during development (in utero, perinatal, (pre)pubertal, or life-long) and investigate functional consequences for tisuse-specific estrogen sensitivity and mammary carcinogenesis in rat models and human pilot intervention studies.

Our hypothesis is that early molecular changes in developing breast tissue will determine breast cancer susceptibility later in life. The knowledge acquired will be crucial for the evaluation of potential prevention strategies.