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

BPA 和邻苯二甲酸盐：对年轻女性乳房炎症标志物和乳房密度的影响

• 批准号: 9320318
• 负责人: Kathleen Frances Arcaro
• 金额: $ 29.98万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9320318
• 关键词: Address; Area; Biological; Biological Assay; Birth; Breast; Breast Cancer Risk Factor; Breast Feeding; Canada; Cancer Etiology; Case-Control Studies; Chemicals; Collection; Development; Discipline of Nursing; Discipline of obstetrics; Employee Strikes; Environmental Pollution; Environmental Risk Factor; Epidemiologic Studies; Exposure to; Food; Household; Human Milk; Inflammation; Inflammatory; Interleukin-6; Laboratories; Lactation; Leptin; Link; Lubricants; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Medical center; Metals; Mexico; Milk; Mothers; Parabens; Phenols; Plasticizers; Population Heterogeneity; Postpartum Period; Predisposition; Premenopause; Prevention strategy; Property; Recruitment Activity; Research; Research Design; Risk; Role; Serum; Specimen; Surface; TNF gene; Techniques; Time; Triclosan; Urine; Woman; adiponectin; bisphenol A; breast density; cancer risk; early life exposure; environmental chemical; estrogenic; human tissue; inflammatory marker; innovation; interest; malignant breast neoplasm; mammary epithelium; personal care products; phthalates; proliferative phase Menstrual cycle; toxicant; triclocarban; urinary; women employment; young woman

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.

项目摘要 双足A（BPA）和邻苯二甲酸盐是用于制造许多家庭和个人的增塑剂 护理产品（例如，BPA用于金属罐的内表面涂层）。这些化合物可以 具有雌激素和炎症特性，可以增加患乳腺癌的风险。乳房密度是 乳腺癌最强的危险因素之一。在最近的一项研究中，BPA和 邻苯二甲酸酯（MEP）与较高水平的乳房乳房密度显着相关。 对于两种化合物，血清水平的女性中的乳房密度高约5个百分点 与无法检测到水平的女性相比，可检测到的中值高于可检测水平。比例可比的 乳房密度的点差异与其他其他乳腺癌风险增加了5％至10％ 流行病学研究。对BPA/邻苯二甲酸酯乳前密度研究中使用的血清测定的担忧 单个时间点的暴露量测量导致了关于其发现的争议，尽管尚不清楚 虚假的积极联系可能会出现。显然需要进一步的研究来验证 发现，尤其是因为不了解基本机制。高尿液水平高的事实 在这种情况下，在绝经前妇女中患乳腺癌风险增加了四倍 在墨西哥进行的对照研究，并在加拿大进行的一项案例对照研究观察到了惊人 绝经前妇女的乳腺癌风险与塑料制造业的就业 在食品罐头中，进一步强调了该领域的研究需求。我们假设高暴露 BPA和一些邻苯二甲酸盐会导致乳房微环境的炎症增加 增加乳腺癌密度和乳腺癌的敏感性。在一种创新的研究方法中，我们将研究 BPA/邻苯二甲酸盐代谢物的尿和牛奶水平之间的关系，乳房中的炎症标记， 和250个护理母亲的乳房密度。 BPA和12个邻苯二甲酸酯代谢产物的尿液水平将是 在两个时间点测量：出生后六周[T0]和停止母乳喂养[T1]六个月。 BPA和钥匙乳腺炎症标记的母乳水平也将在T0处测量。非增强 磁共振成像（MRI）将用于评估T1处的密集百分比。独特的优势 这项研究的是多个时间点暴露测量，选择接受的矩阵 测量这些化学物质，能够直接检查这些化学物质的潜在炎症作用 在乳房微环境中，有机会检查各种年轻妇女的风险。