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最常见的肿瘤，并且每年的新发病例不断增加。然而，患乳腺癌的女性人数和每年新增病例的数量因国家而异。例如，与德国相比，印度的乳腺癌发病率只有三分之一，然而，与世界上40多个国家相比，印度的年新增病例一直是第二高的。通过预防措施应对全球乳腺癌新病例增加的第一步是确定导致肿瘤发展的已知乳腺癌风险因素的分子靶点。尽管各国乳腺癌流行病学有所不同，但主要风险因素似乎具有普遍性：长期暴露于内源性女性和男性性激素及其前体水平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，摄入某些构成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来发挥作用的。这种相互作用可归因于天然食物成分或环境污染物和残留物，其中许多与干扰内源性性激素(内分泌干扰物)的生理活动有关。尽管印度妇女对环境内分泌干扰物的暴露程度较高，但缺乏关于她们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，现在有太多可能的分子靶点，用于化合物与乳腺特异的相互作用，无论是有益的还是不利的结果。这项印度-德国研究项目调查了已知和疑似乳腺癌风险因素对与印度和德国妇女乳腺组织中肿瘤形成相关的分子过程的影响。为了实现这一目标，饮食习惯以及个人内部接触23种环境内分泌干扰物以及血液和乳房组织中内源性性激素水平的质量谱将被量化，并将确定它们对乳房组织内细胞增殖和细胞压力的影响。

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.