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

项目摘要 双酚A（BPA）和邻苯二甲酸酯是用于制造许多家用和个人食品的增塑剂。 护理产品（例如，BPA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。乳腺密度是 乳腺癌的最大危险因素之一。在最近的一项研究中，高水平的BPA和 邻苯二甲酸单乙酯（MEP）与较高的乳腺摄影乳腺密度水平显著相关。 对于这两种化合物，在血清水平为100 mg/kg的女性中， 高于中位数检测水平与妇女相比，无法检测水平。相似的百分比- 乳腺密度的点差异与其他乳腺癌风险增加5%至10%有关。 流行病学研究。对BPA/邻苯二甲酸酯-乳腺密度研究中使用的血清测定的担忧， 单一时间点暴露测量导致了对其结果的争议，尽管其结果尚不清楚 一个虚假的积极联系是如何出现的显然需要进一步的研究来验证 研究结果，特别是因为根本的机制还不清楚。事实上，高MEP尿水平 也与绝经前妇女患乳腺癌的风险增加4倍有关， 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塑料制造业就业之间的关系 以及食品罐头制造业进一步强调了这一领域研究的必要性。我们假设高曝光率 BPA和一些邻苯二甲酸盐导致乳腺微环境炎症增加， 增加乳腺密度和乳腺癌易感性。在一个创新的研究方法，我们将研究 尿和乳汁中BPA/邻苯二甲酸酯代谢物水平之间的关系，乳房中的炎症标志物， 250例初产妇的乳腺密度。尿液中BPA和12种邻苯二甲酸酯代谢物的水平将 在两个时间点测量：出生后6周[T0]和停止母乳喂养后6个月[T1]。 还将在T0时测量BPA和关键乳腺炎性标志物的母乳水平。非增强 将使用磁共振成像（MRI）评估T1时的致密体积百分比。独特的优势 本研究的重点是多个时间点暴露测量，选择可接受的基质， 测量这些化学物质，直接检查这些化学物质的潜在炎症作用的能力， 在乳房微环境中，以及在不同的年轻女性人群中检查风险的机会。

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.