BPA and Phthalates: Effects on Inflammatory Markers in the Breast and Breast Density in Young Women

项目摘要 双酚A(BPA)和邻苯二甲酸酯是许多家庭和个人制造中使用的增塑剂 护理产品(例如，双酚A用于金属罐内表面的涂层)。这些化合物可以 具有雌激素和炎症特性，可能会增加患乳腺癌的风险。乳房密度是 乳腺癌的最强风险因素之一。在最近的一项研究中，循环中高水平的双酚A和 邻苯二甲酸单乙酯(MEP)与较高水平的乳房X光摄影密度显著相关。 对于这两种化合物，在有血清水平的女性中，乳房密度高出约5个百分点 高于可检测到的中位数水平的妇女与无法检测到水平的妇女相比。一个可比的百分比- 乳房密度的点差异与其他地区乳腺癌风险增加5%至10%有关 流行病学研究。对双酚A/邻苯二甲酸盐-乳房密度研究中使用的血清分析和 单时间点暴露测量结果引发了争议，尽管尚不清楚 一种虚假的积极联系怎么会出现。显然需要进一步的研究来证实 调查结果，特别是在根本机制不清楚的情况下。事实上，高MEP尿液水平 在一个病例中，绝经前女性患乳腺癌的风险也增加了四倍- 在墨西哥进行的一项对照研究，以及最近在加拿大进行的一项病例对照研究发现 绝经前妇女乳腺癌风险与从事塑料制造业的关系 在食品罐头方面，进一步强调了在这一领域进行研究的必要性。我们假设高曝光率 双酚A和一些邻苯二甲酸盐会导致乳房微环境炎症增加，这对 与乳房密度增加和乳腺癌易感性有关。在创新的研究方法中，我们将研究 尿液和乳汁中双酚A/邻苯二甲酸酯代谢物、乳房炎症标志物、 250例首次哺乳母亲的乳房密度。尿双酚A和12邻苯二甲酸酯代谢物的水平将是 在两个时间点测量：出生后六周[T0]和停止母乳喂养后六个月[T1]。 母乳中双酚A和关键的乳房炎症标志物的水平也将在T0进行测量。非增强型 磁共振成像(MRI)将用于评估T1时的密度百分比。独一无二的优势 这项研究的主要内容是多时间点曝光测量，选择可接受的矩阵以 测量这些化学物质，直接检查这些化学物质的潜在炎症效应的能力 在乳房微环境中，以及在不同的年轻女性群体中检查风险的机会。

Project Summary Bisphenol A (BPA) and phthalates are plasticizers used in the manufacturing of many household and personal care products (e.g., BPA is used in the coating of the inside surface of metal cans). These compounds can have estrogenic and inflammatory properties that could increase the risk of breast cancer. Breast density is one of the strongest risk factors for breast cancer. In a recent study, high circulating levels of BPA and monoethyl phthalate (MEP) were significantly associated with higher levels of mammographic breast density. For both compounds, breast density was about five percentage points higher among women with serum levels above the median detectable level compared with women with undetectable levels. A comparable percentage- point difference in breast density has been linked with a 5 to 10% increase in breast cancer risk in other epidemiologic studies. Concerns about the serum assay used in the BPA/phthalate-breast density study and the single time-point exposure measurement have led to controversy over its findings although it is not clear how a spurious positive association could have emerged. Further research is clearly needed to verify the findings, especially since the underlying mechanism is not understood. The fact that high MEP urinary levels were also associated with a four-fold increased risk of breast cancer in premenopausal women in a case- control study conducted in Mexico, and that a recent case-control study conducted in Canada observed striking associations between breast cancer risk in premenopausal women and employment in plastics manufacturing and in food canning further underscore the need for research in this area. We hypothesize that high exposure to BPA and some phthalates results in increased inflammation in the breast microenvironment that contributes to increased breast density and breast cancer susceptibility. In an innovative study approach, we will examine the relation between urinary and milk levels of BPA/phthalate metabolites, inflammatory markers in the breast, and breast density in 250 nursing first time mothers. Urinary levels of BPA and 12 phthalate metabolites will be measured at two time points: six weeks after birth [T0] and six months after cessation of breastfeeding [T1]. Breast milk levels of BPA and key breast inflammatory markers will also be measured at T0. Non-enhanced magnetic resonance imaging (MRI) will be used to assess percent dense volume at T1. The unique strengths of this study are the multiple time-point exposure measurements, the selection of accepted matrices to measure these chemicals, the ability to examine the potential inflammatory effects of these chemicals directly in the breast microenvironment, and the opportunity to examine risk in a diverse population of young women.