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

描述(申请人提供)：某些饮食化合物的肠道微生物代谢可以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型大豆苷元转化为马酚。在体外，马酚比大豆苷元具有更强的生物活性。只有25%-50%的人类会产生木马醇。马儿生产中涉及的细菌还没有完全确定，但通过检测大豆消费后血液或尿液中的马儿，很容易确定马儿的生产者。这是假设，马匹生产者可能对异黄酮类干预更敏感，因为他们产生了更具生物活性的代谢物；这得到了几项干预研究的支持。观察性研究的结果还表明，与不生产马豆素的人相比，生产马豆油的人患乳腺癌的风险可能更低；然而，到目前为止，很少有研究在相关人群(即大豆消费者)中评估这一点。我们的具体目标是评估血浆Equol浓度与乳腺癌风险、乳腺纤维囊性疾病以及增殖性和非增殖性乳房疾病(在乳腺癌病例的瘤外组织中确定)之间的关联，在居住在上海的大量明确定义的女性中，中国--由于频繁食用大豆而高度相关的研究人群。作为次要目标，我们将确定马匹生产者患乳腺癌和FBC的风险是否与大豆接触有关，这是通过FFQ和血浆染料木素浓度来衡量的。这项工作将使用之前从乳房自我检查试验及其辅助研究参与者那里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、人口统计和遗传数据。此外，已经对这些女性的血浆大豆苷元和染料木素浓度进行了测量。在这项拟议的研究中，我们将使用一种高灵敏度和特异性的时间分辨荧光免疫分析法来测定325例乳腺癌患者、495例FBC患者和1017名未受影响的女性的血浆样本中的马酚浓度。所有分析都将根据血浆染料木素浓度进行调整，以此作为确定Equol的独立作用的一种手段。我们可获得的大量额外数据将使我们能够针对我们主要和次要目标中的潜在混杂因素进行调整。由于我们将利用作为先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暴露和异黄酮代谢与人类健康相关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这一研究人群的丰富信息，并将有助于指导进一步研究肠道微生物区系对疾病风险的影响。

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.