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：尿中雌激素代谢物在两年的大豆妇女大豆食品中进行了为期两年的大豆试验，其生物活性成分异黄酮被认为与内源性雌激素相互作用，这些雌激素在乳腺癌病因中起着不可或缺的作用。癌症流行病学中的这种小赠款提出了使用现有的尿液样本进行的其他分析，这些尿液样本是在220名年绝经前妇女中为期两年的随机大豆试验的一部分。我们将探索两个假设，以探索大豆对乳腺癌的潜在保护作用，这不是原始研究的一部分，因为当时尚未开发出雌激素和异黄酮尿液代谢物的适当分析技术，但现在可以使用。一个是，大豆食品改变了尿液中尿液中的一系列类固醇雌激素对遗传毒性代谢产物的模式，改变了雌激素代谢。其次，大豆的有益作用只能由具有能够转化dadzein的受试者，这些受试者能够转化dadzein，dadzein是大豆中主要的异黄酮之一，以屈服。拟议的研究的具体目的是探索大豆每天两份对雌激素代谢的细胞色素改变的影响，如尿2-，161-和4-羟基雌激素代谢物的形成所表达的，并检查equolencretor在乳腺癌症中对SOY的响应是否影响了对生物癌症和乳腺癌的响应的反应。在黄体期收集的冷冻尿液样品，并在-80：C中存储在-80：C将分析9个雌激素和代谢产物，并使用液相色谱 - 质谱法分析equol。对于至少一年后具有尿液样本的198名受试者（98名干预受试者和100个对照）中的每个受试者，我们将分析雌激素代谢产物的基线和最终样本，而在两个尿液样本中，将在两种尿液样本中测量，每个女性在干预组中的总isoflavone浓度最高。由于对照组中的受试者没有食用大豆食品，因此无法评估其雌性产生状态。统计分析将通过大豆治疗将混合模型应用于比较雌激素代谢产物的水平和模式，同时考虑到重复的措施。通用线性模型将用于比较雌性状态，即类固醇激素，乳房X线摄影密度和尿雌激素代谢物的不同生物标志物。此外，我们将研究与种族，体重，终生大豆摄入量和其他饮食因素有关的雌性生产者的地位。 公共卫生相关性：项目叙事标题：尿中雌激素代谢物在两年的大豆妇女公共卫生意义之间进行了为期2年的大豆试验：大豆食品的荷尔蒙影响继续在科学和流行的出版物中得到更加强调，并且需要更好地理解，尤其是鉴于对乳腺癌生存的潜在不良影响以及对乳腺癌生存的潜在不良影响以及对胸部癌女性的潜在不良影响。该项目将探讨大豆和异黄酮如何预防乳腺癌的两个假设，并有助于了解大豆食品在乳腺癌发育和预防中的作用。