Urinary Estrogen Metabolites in a 2-year Soy Trial Among Premenopausal Women

描述（由申请人提供）：项目总结标题：绝经前妇女2年大豆试验中的尿雌激素代谢物大豆食品及其生物活性成分黄酮被认为与内源性雌激素相互作用，在乳腺癌的病因学中起着不可或缺的作用。这项癌症流行病学的小额资助建议使用现有的尿液样本进行额外的分析，这些样本是在220名绝经前妇女中进行的为期2年的随机大豆试验的一部分。我们将探讨大豆对乳腺癌的潜在保护作用的两个假设，这两个假设不是原始研究的一部分，因为当时没有开发出测量雌激素和雌激素的尿液代谢物的适当分析技术，但现在已经可用。一个是大豆食品改变了雌激素代谢，通过尿液中的一系列甾体雌激素来评估，以降低遗传毒性代谢产物的模式。第二，大豆的有益效果可能仅由具有能够将大豆中的主要黄酮之一大豆苷元转化为雌马酚的肠道细菌的受试者体验。拟议的研究的具体目的是探索每天两份大豆对雌激素代谢的细胞色素改变的影响，如尿中2-，161-和4-羟基雌激素代谢产物的形成，并检查雌马酚排泄状态是否影响对大豆的反应，如在原始试验和当前项目中测量的乳腺癌风险生物标志物所评估的。将使用液相色谱-质谱法分析在黄体期采集并储存在-80 ℃的冷冻尿样中的9种雌激素和代谢物以及雌马酚。对于198名受试者（98名干预受试者和100名对照）中的每一名，他们在至少一年的干预后都有尿样，我们将分析基线和最终样品的雌激素代谢物，而雌马酚将仅在干预组中每名妇女的两个尿样中测量，其中总雌马酚浓度最高。由于对照组的受试者不食用大豆食品，因此无法评估他们的雌马酚产生状况。统计分析将应用混合模型来比较大豆处理的雌激素代谢物的水平和模式，同时考虑重复测量。一般线性模型将用于通过雌马酚状态比较不同的生物标志物，即，类固醇激素、乳房X线摄影密度和尿雌激素代谢物。此外，我们还将研究雌马酚生产者的地位与种族、体重、终生大豆摄入量和其他饮食因素的关系。 公共卫生相关性：项目叙述标题：绝经前妇女2年大豆试验中的尿雌激素代谢水平公共卫生意义：科学和大众出版物继续强调大豆食品的激素效应，需要更好地理解，特别是考虑到对乳腺癌幸存者和乳腺癌高危妇女中大豆潜在不良影响的新担忧。该项目将探讨大豆和大豆酮如何预防乳腺癌的两种假设，并将有助于了解大豆食品在乳腺癌发展和预防中的作用。

DESCRIPTION (provided by applicant): PROJECT SUMMARY Title: Urinary Estrogen Metabolites in a 2-Year Soy Trial among Premenopausal Women Soy foods and their bioactive ingredients isoflavones are thought to interact with endogenous estrogens which play an integral role in the etiology of breast cancer. This small grant in cancer epidemiology proposes additional analyses using existing urine samples that were collected as a part of a 2-year randomized soy trial among 220 premenopausal women. We will explore two hypotheses for the potential protective effects of soy against breast cancer that were not part of the original study because the appropriate analytical techniques to measure urinary metabolites of estrogens and isoflavones were not developed at the time but are available now. One is that soy foods alter estrogen metabolism as assessed by an array of steroidal estrogens in urine to a pattern of less genotoxic metabolites. Second, beneficial effects from soy may only be experienced by subjects who have intestinal bacteria that are able to convert dadzein, one of the major isoflavones in soy beans, to equol. The specific aims of the proposed study are to explore the effect of two daily servings of soy on cytochrome alterations of estrogen metabolism as expressed in the formation of urinary 2-, 161-, and 4- hydroxy estrogen metabolites and to examine whether equol excretor status influences the response to soy as assessed by biomarkers for breast cancer risk measured in the original trial and in the current project. Frozen urine samples collected during the luteal phase and stored at -80:C will be analyzed for nine estrogens and metabolites and for equol using liquid chromatography-mass spectrometry. For each of the 198 subjects (98 intervention subjects and 100 controls) who have a urine sample after at least one year of intervention, we will analyze the baseline and the final sample for estrogen metabolites, whereas equol will be measured in the two urine samples with the highest total isoflavone concentration for each woman in the intervention group only. Because subjects in the control group were not consuming soy foods, their equol producing status cannot be assessed. The statistical analysis will apply mixed models to compare levels and patterns of estrogen metabolites by soy treatment, while taking into account the repeated measures. General linear models will be used to compare the different biomarkers by equol status, i.e., steroid hormones, mammographic density, and urinary estrogen metabolites. In addition, we will examine equol producer status in relation to ethnicity, body weight, lifetime soy intake, and other dietary factors. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE Title: Urinary Estrogen Metabolites in a 2-year Soy Trial Among Premenopausal Women Public Health Significance: The hormonal effects of soy foods continue to be emphasized in scientific and popular publications and need to be understood better, in particular in light of emerging concerns about potential adverse effects of soy among breast cancer survivors and women at high risk for breast cancer. This project will explore two hypotheses of how soy and isoflavones may protect against breast cancer and will help to understand the role of soy foods in breast cancer development and prevention.