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(申请人提供)：项目摘要标题：在绝经前妇女中进行的为期两年的大豆试验中的尿雌激素代谢物大豆食品及其活性成分异黄酮被认为与内源性雌激素相互作用，后者在乳腺癌的病因中起着不可或缺的作用。这项癌症流行病学的小额拨款建议使用现有的尿样进行额外的分析，这些尿样是在220名绝经前妇女中进行的为期两年的随机大豆试验的一部分。我们将探索大豆对乳腺癌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，因为当时还没有开发出适当的分析技术来测量尿中雌激素和异黄酮代谢物，但现在已经可以使用。其中之一是，大豆食品改变了雌激素代谢，根据尿液中一系列类固醇雌激素的评估，转变为遗传毒性较小的代谢物模式。其次，只有那些肠道细菌能够将大豆中的主要异黄酮之一--大豆黄素转化为马酚的受试者，才可能体验到大豆的有益效果。拟议研究的具体目的是探索每天食用两种大豆对雌激素代谢的细胞色素变化的影响，表现为尿液中2-、161-和4-羟基雌激素代谢物的形成，并检查马儿排泄物状态是否影响原始试验和当前项目中测量的乳腺癌风险生物标记物评估的大豆的反应。在黄体期收集并储存在-80℃下的冰冻尿样将用液相色谱-质谱仪分析九种雌激素和代谢物以及马酚。对于在干预至少一年后有尿样的198名受试者(98名干预者和100名对照组)，我们将分析基线和最终样本中的雌激素代谢物，而只在干预组中每个女性的总异黄酮浓度最高的两个尿样中测量雌酚。因为控制组的受试者没有食用豆类食品，所以他们的马醇产生状况无法评估。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，同时考虑到重复的措施。一般的线性模型将被用来比较不同的生物标志物，即类固醇激素、乳房X光检查密度和尿雌激素代谢物。此外，我们还将检查与种族、体重、终生大豆摄入量和其他饮食因素有关的马匹生产者地位。 公共卫生相关性：项目叙述标题：在绝经前妇女中进行的为期两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的荷尔蒙效应，需要更好地了解，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关注。该项目将探索大豆和异黄酮如何预防乳腺癌的两个假说，并将有助于理解大豆食品在乳腺癌发展和预防中的作用。