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

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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.