Impact of environmental endocrine disruptors, diet, and lifestyle on sex hormone levels and consequences thereof in human breast tissues of Indian and German women

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Breast cancer has become the most frequent tumor in women all over the world and the number of new cases per year rises continually. Yet, the number of women with breast cancer and the annual increase in new cases differ between countries. India for example exhibits only one third of the breast cancer rate compared to Germany, however, the annual increase in new cases has been the second highest compared to over 40 countries world wide. The first step to counteract the worldwide increase in new breast cancer cases by preventive measures, represents the identification of the molecular targets of known breast cancer risk factors contributing to tumor development. Despite all differences in breast cancer epidemiology between countries, the main risk factor seems universal: prolonged exposure to increased levels of the endogenous female and male sex hormones and their precursors as well as all factors resulting in their increase (i.e. intake of drugs releasing female sex hormones, adiposity). Likewise, consumption of certain food categories posing a risk for breast cancer seems to act -among other possible mechanisms- via interaction with the endogenous sex hormone system. Such interaction can be attributed to natural food constituents or environmental contaminants and residues of which many have been associated with interference with the physiological actions of endogenous sex hormones (endocrine disruptors). Although a higher exposure of Indian women to environmental endocrine disruptors has been discussed, qualitative and quantitative data on the inner exposure of their breast tissues to endocrine disruptors are lacking. Moreover, it was recently shown that sex hormone levels within the breast seem not to depend exclusively on levels in blood but also on biotransformation processes within the breast tissue. Thus, there is now a plethora of possible molecular targets for mammary-specific interactions of compounds with either beneficial or adverse outcome. This Indo-German research project investigates the impact of known and suspected breast cancer risk factors on molecular processes relevant to tumor formation in breast tissues from Indian and German women. To achieve this goal, dietary habits as well as individual inner exposure to 23 environmental endocrine disruptors and levels of endogenous sex hormones in blood and breast tissue will be quantified mass spectrometrically and their influence on cell proliferation and cellular stress within the breast tissue will be identified.