Breast Cancer, Benign Breast Disease, and Isoflavone Metabolism in Chinese Women

描述（由申请人提供）：某些膳食化合物的肠道微生物代谢可产生比其前体更具生物活性的代谢物。一个例子是肠道细菌将大豆异黄酮大豆黄酮转化为雌马酚。在体外，雌马酚比大豆苷元更具生物活性。只有25-50%的人产生雌马酚。参与产生马酚的细菌尚未被完全鉴定，但通过测量食用大豆后血液或尿液中的马酚含量，很容易识别出马酚的产生者。据推测，雌马酚生产者可能对异黄酮干预更敏感，因为它们产生的代谢产物更具生物活性；这得到了几项干预研究的支持。观察性研究的结果还表明，与不产生雌马酚的人相比，产生雌马酚的人患乳腺癌的风险可能更低；然而，迄今为止很少有研究在相关人群（即大豆消费者）中评估这一点。我们的具体目的是评估血浆雌马酚浓度与乳腺癌、纤维囊性乳腺疾病（FBC）以及增殖性和非增殖性FBC（由乳腺癌病例的肿瘤外组织确定）风险之间的关系，研究对象是居住在中国上海的大量明确定义的女性人群——由于频繁食用大豆，这是一个高度相关的研究人群。作为次要目的，我们将通过FFQ和血浆染料木素浓度来确定马酚产生者的乳腺癌风险和FBC风险是否与大豆暴露有关。这项工作将使用先前从乳房自检试验及其辅助研究的参与者收集的血浆样本进行，并将利用广泛收集的组织学、生殖、饮食、人口统计学和遗传数据。此外，已经测量了这些妇女血浆中的大豆黄素和染料木素浓度。在拟议的研究中，我们将使用高灵敏度和特异性时间分辨荧光免疫分析法测定325例乳腺癌病例、495例FBC病例和1017例未受影响妇女的血浆样本中的雌马酚浓度。所有的分析将调整血浆染料木素浓度作为确定马雌酚独立作用的手段。我们可以获得的大量额外数据将使我们能够调整主要和次要目标中的潜在混杂因素。因为我们将利用作为以前研究的一部分收集的样本和数据，我们将能够以高效和经济的方式实现我们的研究目标。这项研究产生的数据将为参与评估大豆接触和异黄酮代谢与人类健康关系的科学界提供非常受欢迎的信息。此外，收集的额外数据将增加关于该研究人群的丰富信息，并将有助于指导肠道微生物群对疾病风险影响的进一步研究。

DESCRIPTION (provided by applicant): The intestinal microbial metabolism of certain dietary compounds can produce metabolites that are more biologically active than their precursors. One example is the gut bacterial conversion of the soy isoflavone daidzein to equol. In vitro, equol is more biologically active than daidzein. Only 25-50% of humans produce equol. The bacteria involved in equol production have not been fully characterized, but equol-producers are easily identified by measuring equol in blood or urine after soy consumption. It has been hypothesized that equol-producers may be more responsive to isoflavone interventions because of their production of a more bioactive metabolite; this is supported by several intervention studies. Results of observational studies also suggest that, compared with equol non-producers, equol-producers may be at a lower risk of breast cancer; however, few studies to date have assessed this in relevant populations (i.e., soy consumers). Our specific aims are to evaluate the association between plasma equol concentration and the risk of breast cancer, fibrocystic breast conditions (FBC), and proliferative and non-proliferative FBC (as determined in extra-tumoral tissue from breast cancer cases), in a large, well-defined population of women living in Shanghai, China -- a highly relevant study population due to frequent soy consumption. As secondary aims, we will determine whether the risk of breast cancer and risk of FBC among equol-producers is associated with soy exposure, as measured by FFQ and plasma genistein concentration. This work will be conducted using previously collected plasma samples from participants in the Breast Self Examination Trial and its ancillary studies, and will make use of an extensive collection of histologic, reproductive, dietary, demographic, and genetic data. In addition, plasma daidzein and genistein concentrations have already been measured in these women. For the proposed study, we will determine equol concentration in plasma samples from 325 breast cancer cases, 495 FBC cases, and 1017 unaffected women using a highly sensitive and specific time-resolved fluoroimmunoassay. All analyses will be adjusted for plasma genistein concentration as a means of determining the independent effect of equol. The large amounts of additional data available to us will allow us to adjust for potential confounders in our primary and secondary aims. Because we will utilize samples and data that were collected as part of previous studies, we will be able to fulfill our study aims in an efficient and cost-effective manner. Data generated by this study will provide highly sought-after information for the scientific community involved in assessing soy exposure and isoflavone metabolism in relation to human health. Furthermore, the additional data collected will add to the wealth of information available on this study population and will help guide further research on the impact of the gut microbiota on disease risk.