Breast and Bone Density: Impact of Colonic Environment

描述（由申请人提供）：女性一生中过多地接触雌激素会增加患乳腺癌的风险。在肠道中，微生物群在雌激素代谢中起着重要作用；因此，宿主细菌种群的个体间差异可能是雌激素暴露和最终乳腺癌风险的决定因素。结肠微生物将大豆异黄酮大豆黄酮转化为雌马酚是一种独特的肠道细菌群的生物标志物。不管大豆的摄入量如何，有能力产生雌马酚的女性的荷尔蒙水平与乳腺癌的风险较低有关。只有大约三分之一的人体内有能够产生马酚的细菌，而马酚的产生状态可以很容易地从服用大豆3天后收集的尿液样本中确定。我们假设产生雌马酚的女性对雌激素的累积接触量较低。我们建议研究马酚生成状态与雌激素累积暴露标志物（乳腺和骨密度）、选定的类固醇激素和SHBG以及2-羟孕酮：16 α -羟孕酮（2- ohe1:16 α - ohe1）比值之间的关系。作为次要目标，我们将研究密度和雌激素测量之间的关系，并探索饮食和其他暴露对雌马酚产生表型的影响。我们将从团体健康合作社（GHC）内招募750名健康的绝经前志愿者，年龄在40-45岁之间，在过去一年中接受过乳房x光检查。在GHC，乳房x光片根据美国放射学院乳腺成像和数据报告系统（BI-RADS）的密度分类。我们将在BI-RADS组中招募250名女性：1和2加起来，3和4。将收集有关一般健康、人口统计、饮食摄入、体育活动、生育史和风险因素的数据。经过3天的大豆挑战，妇女将在第四天收集第一次空尿用于分析雌马酚。每位女性将被划分为雌马酚产生者和非产生者。其中150名妇女还将被邀请到诊所进行DEXA测量她们的髋部和脊柱骨密度，并提供血液样本用于类固醇激素分析，并提供尿样用于2-OHE1和16 - α -OHE1分析。将检查雌马酚生成状态在乳腺密度、骨密度、类固醇激素、SHBG和2-OHEI:16 α - ohe1方面的差异。此外，我们将评估雌马酚的产生是否独立于与这些指标相关的其他因素，预测乳腺密度、骨密度、类固醇激素、SHBG和2-OHE 1:16ct-OHE 1的差异。如果雌马酚产生者表型可以预测累积雌激素暴露/代谢的差异，它可能作为乳腺癌风险的早期标志。

DESCRIPTION (provided by applicant): Greater exposure to estrogen throughout a woman's lifetime increases her risk of developing breast cancer. In the gut, microflora play a significant role in the metabolism of estrogens; therefore, inter-individual differences in host bacterial populations may be a determinant of estrogen exposure and ultimately of breast cancer risk. Colonic microfloral conversion of the soy isoflavone daidzein to equol is a biomarker of a unique intestinal bacterial population. Irrespective of soy intake, women with the capacity to produce equol have hormonal profiles associated with a lower risk of breast cancer. Only about a third of individuals have the yet-to-be-identified bacteria capable of producing equol, and equol-producer status can be determined readily from a urine sample collected after a 3-day soy challenge. We postulate that women who are equol-producers have lower cumulative exposure to estrogens. We propose to examine relationships between equol-producer status and markers of cumulative estrogen exposure (breast and bone densities), selected steroid hormones and SHBG, and the 2-hydroxyestrone: 16alpha-hydroxyestrone (2-OHE1:16alpha-OHE 1) ratio. As secondary aims we will examine associations between the density and estrogen measures, and explore the impact of diet and other exposures on equol-producer phenotype. We will recruit 750 healthy, premenopausal volunteers from within Group Health Cooperative (GHC), aged 40-45 years, and who have had a screening mammogram in the past year. At GHC, mammograms are classified into categories of density according to the American College of Radiology Breast Imaging and Data Reporting System (BI-RADS). We will recruit 250 women each within BI-RADS Groups: 1 and 2 combined, 3, and 4. Data on general health, demographics, dietary intake, physical activity, reproductive history and risk factors will be collected. After a 3-day soy challenge, women will collect a first-void urine on the fourth day for analysis of equol. Each woman will be classified as an equol-producer or nonproducer. 150 of the women will also be invited for a clinic visit to have their hip and spine bone densities measured by DEXA, and to provide a blood sample for steroid hormone analysis and a spot urine for 2-OHE1 and 16alpha- OHE1 analysis. Differences in breast density, bone density, steroid hormones, SHBG, and 2-OHEI:16alpha-OHE1 by equol producer status will be examined. In addition, we will evaluate whether equol production predicts differences in breast density, bone density, steroid hormones, SHBG, and 2-OHE 1:16ct-OHE 1 independently of other factors associated with these measures. If equol-producer phenotype can predict differences in cumulative estrogen exposure / metabolism, it may serve as an early marker of breast cancer risk.