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

乳腺癌已成为全世界女性中最常见的肿瘤，每年的新病例数不断上升。然而，患乳腺癌的妇女人数和每年新病例的增长在各国之间有所不同。例如，与德国相比，印度的乳腺癌发病率仅为三分之一，然而，与全世界40多个国家相比，印度新病例的年增长率位居第二。通过预防措施对抗全球范围内新发乳腺癌病例增加的第一步，代表了已知乳腺癌危险因素对肿瘤发展的分子靶标的识别。尽管各国之间的乳腺癌流行病学存在各种差异，但主要的危险因素似乎是普遍的：长期暴露于内源性女性和男性性激素及其前体水平的增加，以及导致其增加的所有因素（即摄入释放女性性激素的药物、肥胖）。同样，在其他可能的机制中，食用某些有患乳腺癌风险的食物似乎是通过与内源性性激素系统的相互作用起作用的。这种相互作用可归因于天然食品成分或环境污染物和残留物，其中许多与内源性性激素（内分泌干扰物）的生理作用干扰有关。虽然讨论了印度妇女对环境内分泌干扰物的较高暴露，但缺乏关于其乳房组织内部暴露于内分泌干扰物的定性和定量数据。此外，最近的研究表明，乳房内的性激素水平似乎不仅取决于血液中的水平，还取决于乳房组织内的生物转化过程。因此，现在有大量可能的分子靶标用于具有有益或不利结果的化合物的乳腺特异性相互作用。这个印度-德国研究项目调查了已知和疑似乳腺癌危险因素对印度和德国妇女乳腺组织中肿瘤形成相关分子过程的影响。为了实现这一目标，饮食习惯以及个体内部对23种环境内分泌干扰物的暴露以及血液和乳腺组织中内源性性激素的水平将被质谱量化，并将确定它们对乳腺组织内细胞增殖和细胞应激的影响。

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.