Perfluoroalkyl substances and breast cancer tissue biomarkers

全氟烷基物质与乳腺癌组织生物标志物

• 批准号: 10738987
• 负责人: Katherine Whitney Reeves
• 金额: $ 40.53万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-07 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10738987
• 关键词: Acinus organ component; Address; Affect; Aging; Agreement; Biological Assay; Biological Monitoring; Blood; Blood specimen; Breast; Breast Cancer Risk Factor; Breast Carcinogenesis; Breast Feeding; Carcinogens; Childbirth; Collection; Computer software; Data; Development; Diagnostic; Digital Mammography; Environmental Pollution; Exploratory/Developmental Grant; Exposure to; Future; Goals; Health; Human; Human Milk; Investigation; Laboratories; Laboratory Study; Literature; Mammary Gland Parenchyma; Mammary gland; Mammographic Density; Mammography; Measurable; Measurement; Measures; Medical History; Morphology; PPAR alpha; Pathway interactions; Physiological; Poly-fluoroalkyl substances; Population; Postmenopause; Predisposition; Production; Public Health; Reporting; Reproductive History; Resistance; Resources; Sample Size; Sampling; Serum; Stains; Structure; Sulfate; Terminal Ductal Lobular Unit; Time; Tissue Banks; Tissue Donations; Tissue Sample; Water; Work; bioaccumulation; biobank; cancer risk; carcinogenesis; carcinogenicity; consumer product; cost; epidemiologic data; epidemiology study; experience; experimental study; healthy volunteer; human tissue; innovation; insight; malignant breast neoplasm; mammary gland development; milk production; novel; perfluorooctane; perfluorooctanoic acid; programs; steroid hormone; tissue biomarkers; volunteer; Acinus organ component; Address; Affect; Aging; Agreement; Biological Assay; Biological Monitoring; Blood; Blood specimen; Breast; Breast Cancer Risk Factor; Breast Carcinogenesis; Breast Feeding; Carcinogens; Childbirth; Collection; Computer software; Data; Development; Diagnostic; Digital Mammography; Environmental Pollution; Exploratory/Developmental Grant; Exposure to; Future; Goals; Health; Human; Human Milk; Investigation; Laboratories; Laboratory Study; Literature; Mammary Gland Parenchyma; Mammary gland; Mammographic Density; Mammography; Measurable; Measurement; Measures; Medical History; Morphology; PPAR alpha; Pathway interactions; Physiological; Poly-fluoroalkyl substances; Population; Postmenopause; Predisposition; Production; Public Health; Reporting; Reproductive History; Resistance; Resources; Sample Size; Sampling; Serum; Stains; Structure; Sulfate; Terminal Ductal Lobular Unit; Time; Tissue Banks; Tissue Donations; Tissue Sample; Water; Work; bioaccumulation; biobank; cancer risk; carcinogenesis; carcinogenicity; consumer product; cost; epidemiologic data; epidemiology study; experience; experimental study; healthy volunteer; human tissue; innovation; insight; malignant breast neoplasm; mammary gland development; milk production; novel; perfluorooctane; perfluorooctanoic acid; programs; steroid hormone; tissue biomarkers; volunteer

PROJECT SUMMARY Per- and polyfluoroalkyl substances (PFAS) are possible carcinogens and have demonstrated detrimental effects on the mammary gland in experimental studies. PFAS are widely used in non-stick, water-resistant, and stain-resistant coatings for consumer products. Nearly all U.S. residents have detectable PFAS in their blood, and their environmental persistence and potential for bioaccumulation raises significant concerns about their long-term health effects. Epidemiologic studies offer preliminary evidence that exposure to certain PFAS may be associated with a doubling of breast cancer risk, and laboratory studies also support breast carcinogenesis following PFAS exposure. Exploring morphological features of human breast tissue can provide important insight on breast carcinogenesis and the impacts of specific exposures. No prior studies have directly explored how human breast tissue is affected by PFAS exposure. Terminal ductal lobular unit (TDLU) involution and mammographic density (MD) are features of human breast tissue that are strongly and independently associated with breast cancer risk and likely lie on the causal pathway. Our overall goal is to understand if PFAS contribute to breast cancer development. Toward this goal, we propose a novel investigation to understand if serum concentrations of common PFAS are associated with TDLU involution and MD. We will leverage the unique resources of the Susan G. Komen for the Cure Tissue Bank (KTB) biorepository, which includes ~9,000 samples of breast tissue donated by healthy volunteers along with relevant epidemiologic data (e.g. medical history, reproductive history); a subset of volunteers also provided a blood sample and/or access to mammograms. We will select the 286 postmenopausal KTB donors with available: a) stored serum sample, b) prior TDLU measurements, and c) mammogram. We will measure a panel of common PFAS in serum samples using a validated assay at a highly experienced and reputable laboratory. We will address the following Specific Aims: to assess associations between serum PFAS concentrations and quantitative measures of 1) TDLU involution and 2) MD. We have an excellent opportunity to capitalize on pre-existing data and biospecimens from the KTB for an innovative exploration of PFAS and these breast tissue features, each of which is independently predictive of breast cancer risk. The proposed work will provide insight on physiologic mechanisms and generate critical preliminary data critical for future larger epidemiologic studies of PFAS and breast cancer risk. As PFAS exposure is ubiquitous, even a small association with breast cancer risk would substantially impact public health.

项目摘要 每种和多氟烷基物质（PFA）是可能的致癌物，并且表现出有害的 在实验研究中对乳腺的影响。 PFA被广泛用于非粘，防水和 用于消费产品的耐染色涂料。几乎所有美国居民的血液中都有可检测的PFA， 他们的环境持久性和生物积累的潜力引起了人们对其的重大关注 长期健康影响。流行病学研究提供了初步证据，表明某些PFA的暴露可能 与乳腺癌风险增加一倍有关，实验室研究也支持乳腺癌发生 PFAS暴露后。探索人类乳腺组织的形态特征可以提供重要的 洞察乳腺癌发生和特定暴露的影响。没有直接探索先前的研究 人类乳腺组织如何受到PFA暴露的影响。末端导管叶单位（TDLU）的相关性和 乳腺X线摄影密度（MD）是人类乳腺组织的特征，它们是强烈而独立的 与乳腺癌风险相关，可能位于因果途径上。我们的总体目标是了解是否 PFA有助于乳腺癌发展。为了实现这一目标，我们提出了一项新颖的调查 了解普通PFA的血清浓度是否与TDLU相关性和MD相关。我们将 利用Susan G. Komen的独特资源用于治疗组织库（KTB）生物库 包括约9,000个由健康志愿者捐赠的乳腺组织样本以及相关的流行病学数据 （例如病史，生殖史）；一部分志愿者还提供了血液样本和/或通道 到乳房X线照片。我们将选择可用的286个绝经后KTB供体：a）存储的血清样本， b）先前的TDLU测量值和c）乳房X线照片。我们将测量一组普通PFA在血清中 在经验丰富且著名的实验室使用经过验证的测定的样品。我们将解决 以下特定目的：评估血清PFA浓度与定量之间的关联 1）tdlu的措施和2）MD。我们有一个很好的机会来利用已有的数据 来自KTB的生物测量，用于对PFA和这些乳腺组织特征进行创新探索 其中独立预测乳腺癌的风险。拟议的工作将提供有关 生理机制并生成关键的初步数据，对于将来的更大的流行病学研究至关重要 PFA和乳腺癌风险。由于PFA的暴露无处不在，甚至与乳腺癌的相关性很小 风险将大大影响公共卫生。