Perfluoroalkyl substances and breast cancer tissue biomarkers

项目总结 全氟和多氟烷基物质(PFAS)是可能的致癌物质，已证明是有害的 在实验研究中对乳腺的影响。全氟化铝广泛应用于不粘、防水和 用于消费品的防污涂料。几乎所有美国居民的血液中都有可检测到的全氟辛烷磺酸， 它们在环境中的持久性和生物积累的潜力引起了人们对其 对健康的长期影响。流行病学研究提供了接触某些全氟辛烷磺酸的初步证据 与乳腺癌风险翻倍有关，实验室研究也支持乳腺癌的发生 在暴露于全氟辛烷磺酸之后。探索人类乳房组织的形态特征可以提供重要的 对乳腺癌发生和特定暴露的影响的洞察。以前的研究没有直接探索过 人类乳房组织如何受到全氟辛烷磺酸暴露的影响。末梢导管小叶单位(TDLU)退缩 乳腺X线摄影密度(MD)是人类乳腺组织的特征，具有很强的独立性 与乳腺癌风险相关，并可能存在于因果关系中。我们的总体目标是了解 全氟辛烷磺酸有助于乳腺癌的发展。为了实现这一目标，我们提出了一项新的调查 了解血清中常见的PFAS浓度是否与TDLU退缩和MD有关。我们会 利用苏珊·G·科门为治愈组织库(KTB)生物资源库提供的独特资源， 包括由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 到乳房X光检查。我们将选择286名绝经后KTB捐赠者，并提供：a)保存的血清样本， B)先前的TDLU测量，以及c)乳房X光检查。我们将在血清中检测一组常见的PFAS 在经验丰富且信誉卓著的实验室使用经过验证的化验方法采集样品。我们将解决 以下特定目标：评估血清PFAS浓度和定量 测量1)TDLU卷曲和2)MD。我们有一个极好的机会来利用现有的数据 和来自KTB的生物标本，用于对PFAS和这些乳腺组织特征的创新探索，每一个 它们可以独立地预测乳腺癌的风险。拟议的工作将提供关于 生理机制，并生成关键的初步数据，对未来更大规模的流行病学研究至关重要 全氟辛烷磺酸与乳腺癌风险。由于接触全氟辛烷磺酸无处不在，甚至与乳腺癌有很小的联系。 风险将极大地影响公众健康。

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.