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

在绝经前妇女中进行的为期 2 年的大豆试验中的尿雌激素代谢物

• 批准号: 8034695
• 负责人: GERTRAUD MASKARINEC
• 金额: $ 6.63万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2013-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8034695
• 关键词: Accounting; Adverse effects; Bacteria; Biological Markers; Body Weight; Cancer Survivor; Control Groups; Cytochromes; Development; Dietary Factors; Estrogen Metabolism; Estrogen Metabolism Alteration; Estrogens; Ethnic Origin; Etiology; Freezing; Grant; High Risk Woman; Hormonal; Intake; Intervention; Intestines; Isoflavones; Light; Linear Models; Luteal Phase; Mammographic Density; Measures; Modeling; Pattern; Play; Premenopause; Prevention; Public Health; Publications; Randomized; Role; Sampling; Soy Foods; Soybeans; Steroidal Estrogen; Techniques; Time; Urine; Woman; cancer epidemiology; cancer risk; equol; experience; group intervention; liquid chromatography mass spectrometry; malignant breast neoplasm; protective effect; public health relevance; response; soy; soy protein isolate; steroid hormone; urinary

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.

描述（由申请人提供）：项目摘要标题：绝经前妇女为期 2 年的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异黄酮被认为与内源性雌激素相互作用，而内源性雌激素在乳腺癌病因学中发挥着不可或缺的作用。这笔癌症流行病学小额资助建议使用现有尿液样本进行额外分析，这些样本是在 220 名绝经前女性中进行的为期 2 年的随机大豆试验中收集的。我们将探讨大豆对乳腺癌的潜在保护作用的两个假设，这两个假设不属于原始研究的一部分，因为当时尚未开发出测量雌激素和异黄酮尿液代谢物的适当分析技术，但现在已经可用。其一是，根据尿液中一系列类固醇雌激素的评估，大豆食品会改变雌激素代谢，使其成为遗传毒性较小的代谢物。其次，只有肠道细菌能够将大豆黄酮（大豆中的主要异黄酮之一）转化为雌马酚的受试者才能体验到大豆的有益作用。拟议研究的具体目的是探讨每日两份大豆对雌激素代谢细胞色素改变的影响（以尿液 2-、161- 和 4- 羟基雌激素代谢物的形成表示），并检查雌马酚排泄状态是否影响对大豆的反应，正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那样。将使用液相色谱-质谱法分析黄体期期间收集并储存在 -80:C 的冷冻尿液样本中的九种雌激素和代谢物以及雌马酚。对于干预至少一年后收集尿液样本的 198 名受试者（98 名干预受试者和 100 名对照）中的每一位，我们将分析基线和最终样本中的雌激素代谢物，而雌马酚将仅在干预组中每位女性总异黄酮浓度最高的两份尿液样本中进行测量。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后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比较雌马酚状态的不同生物标志物，即类固醇激素、乳房X线密度和尿雌激素代谢物。此外，我们还将研究雌马酚生产者与种族、体重、终生大豆摄入量和其他饮食因素的关系。 公共健康相关性：项目叙述标题：绝经前妇女为期 2 年的大豆试验中的尿雌激素代谢物公共卫生意义：科学和流行出版物继续强调大豆食品的荷尔蒙影响，需要更好地理解，特别是考虑到人们越来越担心大豆对乳腺癌幸存者和乳腺癌高危女性的潜在不利影响。该项目将探讨大豆和异黄酮如何预防乳腺癌的两个假设，并将有助于了解大豆食品在乳腺癌发展和预防中的作用。