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

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.

项目概要 全氟烷基物质和多氟烷基物质 (PFAS) 是可能的致癌物，并已被证明有害 实验研究中对乳腺的影响。 PFAS广泛应用于不粘、防水、 消费品的防污涂料。几乎所有美国居民的血液中都检测到了 PFAS， 它们的环境持久性和生物累积潜力引起了人们对其的严重关注 长期健康影响。流行病学研究提供了初步证据，表明接触某些 PFAS 可能会 与乳腺癌风险加倍相关，实验室研究也支持乳腺癌发生 接触 PFAS 后。探索人类乳腺组织的形态特征可以提供重要的信息 对乳腺癌发生和特定暴露影响的深入了解。先前的研究没有直接探索过 人类乳腺组织如何受到 PFAS 暴露的影响。终末导管小叶单位 (TDLU) 复旧和 乳房X线密度（MD）是人类乳腺组织的特征，这些特征强烈且独立 与乳腺癌风险相关，并且可能存在因果关系。我们的总体目标是了解是否 PFAS 有助于乳腺癌的发展。为了实现这一目标，我们提出一项新颖的调查 了解常见 PFAS 的血清浓度是否与 TDLU 退化和 MD 相关。我们将 利用 Susan G. Komen 的独特资源来建立 Cure Tissue Bank (KTB) 生物样本库， 包括健康志愿者捐赠的约 9,000 个乳腺组织样本以及相关流行病学数据 （例如病史、生育史）；一部分志愿者还提供了血液样本和/或访问权限 乳房X光检查。我们将选择 286 名绝经后 KTB 捐献者，其中包括：a) 储存的血清样本， b) 先前的 TDLU 测量，以及 c) 乳房 X 光检查。我们将测量血清中的一组常见 PFAS 在经验丰富且信誉良好的实验室中使用经过验证的检测来获取样品。我们将解决 以下具体目标：评估血清 PFAS 浓度与定量之间的关联 1) TDLU 合合和 2) MD 的测量。我们有一个很好的机会来利用已有的数据 和来自 KTB 的生物样本，用于对 PFAS 和这些乳腺组织特征进行创新探索，每个 其中可以独立预测乳腺癌风险。拟议的工作将提供以下方面的见解： 生理机制并生成对未来更大规模的流行病学研究至关重要的关键初步数据 PFAS 和乳腺癌风险。由于 PFAS 暴露无处不在，即使与乳腺癌有很小的关联 风险将严重影响公众健康。