Exposure to per- and polyfluoroalkyl substances (PFAS) and risk of cancer in children

接触全氟烷基物质和多氟烷基物质 (PFAS) 与儿童患癌症的风险

基本信息

批准号：
10310918
负责人：
Catherine Metayer
金额：
$ 64.39万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-03 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10310918
关键词：
Accounting Adolescent Adult Age Archives Area Attention Biological Markers Biological Monitoring Birth Blood Blood specimen Body Burden Breast Feeding Calibration California Cancer Cluster Chemicals Child Childhood Leukemia Communities County Data Diet Drug Kinetics Dust Environment Environmental Engineering technology Environmental Health Ethnic Origin Exposure to Food Geographic Locations Health Home House Dust Human Infant Ingestion Institution Intake Kidney Knowledge Laboratories Life Link Los Angeles Lymphoma Malignant Childhood Neoplasm Malignant Neoplasms Malignant neoplasm of brain Measurement Measures Methodology Methods Modeling Mothers Neonatal Neuraxis Newborn Infant Oranges Outcome Participant Pediatric epidemiology Phase Population Pregnancy Race Renal carcinoma Reporting Research Research Personnel Residential Mobility Resources Rhabdomyosarcoma Risk Risk Estimate Route Sampling Serum Site Spottings Statistical Data Interpretation Testing Testis Thyroid Gland Translational Research Universities Water age group analytical method cancer epidemiology cancer risk cancer site case control contaminated drinking water contaminated water design drinking water early childhood early life exposure early onset epidemiology study exposure route high risk improved innovation leukemia novel older patient pharmacokinetic model postnatal prenatal prenatal exposure programs residence screening sex synergism virtual

项目摘要

PROJECT SUMMARY/ABSTRACT Per- and polyfluoroalkyl substances (PFAS) have been used in many manufacturing and commercial products in recent decades, resulting in widespread and persistent contamination despite the phasing out of early compounds such as PFOS and PFOA. Routes of PFAS exposure to humans vary by age; while exposures in infants and children are commonly from breastfeeding and ingestion of settled dust, adolescents and adults are primarily exposed through food and water. PFAS have been associated with several adverse health outcomes, including cancer in adults. Despite several reports of childhood cancer clusters in PFAS-contaminated areas, and potentially higher body burdens in children compared to adults, no studies have systematically assessed cancer risk in children, due, in part to the relative rarity of childhood cancer. We propose to conduct the first study of PFAS and cancer in children, by integrating the expertise of investigators from four institutions, forming a transdisciplinary virtual consortium with expertise in pediatric and cancer epidemiology, and environmental engineering and health sciences. Using innovative methodology, this virtual consortium will characterize PFAS from the most relevant routes of exposure by examining PFAS in drinking water (Aim 1), newborn and pregnancy blood samples (Aim 2), and household dust (Aim 3) during vulnerable exposure windows from pregnancy through early childhood, and subsequent risk of developing childhood cancer. We will focus on cancers that have been reported previously in communities and groups known to have high exposures to PFAS, such as leukemia, rhabdomyosarcoma, lymphoma, and cancers of the brain, central nervous system, kidney, testis, and thyroid. We will leverage two existing California childhood cancer studies with complementary designs offering large number of childhood cancer cases and controls with residential information, and with access to blood and dust samples for subsets. PFAS water exposure assessment, we will use a Bayesian pharmacokinetic calibration approach that combines measured drinking water concentrations with measured serum biomarkers to provide improved exposure estimates. We will also combine targeted and non-targeted mass spectrometric strategies to measure PFAS in blood and dust samples. There will be synergy between the three research aims by overlapping study participants (Aims 1 and 2), coordinating laboratory analyses (Aims 2 and 3) and statistical analyses (Aims 1, 2, 3), and by paying special attention to leukemia--the most common childhood cancer (Aims 1, 2, 3). The ViCTER Consortium will be supported by an Administrative and Scientific Oversight Core to coordinate and integrate resources and activities of the three research aims. With our unique resources, novel methods, and complementary expertise, this proposal responds to the urgent need of assessing population cancer risk to children related to PFAS.

项目概要/摘要全氟烷基物质和多氟烷基物质 (PFAS) 已用于许多制造和商业产品近几十年来，尽管逐步淘汰了早期污染，但仍导致广泛和持续的污染 PFOS 和 PFOA 等化合物。人类接触 PFAS 的途径因年龄而异；同时曝光于婴儿和儿童通常因母乳喂养和摄入沉降的灰尘而感染，青少年和成人则因母乳喂养和摄入沉降的灰尘而感染主要通过食物和水接触。 PFAS 与多种不良健康结果有关，包括成人癌症。尽管有几份关于 PFAS 污染地区儿童癌症集群的报道，与成人相比，儿童的身体负担可能更高，但没有研究系统评估儿童患癌症的风险较高，部分原因是儿童癌症相对罕见。我们建议首先进行 PFAS 与儿童癌症的研究，通过整合四个机构研究人员的专业知识，形成一个跨学科的虚拟联盟，拥有儿科和癌症流行病学以及环境方面的专业知识工程和健康科学。该虚拟联盟将使用创新方法来描述 PFAS 的特征通过检查饮用水（目标 1）、新生儿和妊娠中的 PFAS 来确定最相关的暴露途径从怀孕到怀孕期间的易受暴露窗口期间的血液样本（目标 2）和家庭灰尘（目标 3）儿童早期，以及随后患儿童癌症的风险。我们将重点关注已发现的癌症此前曾报道在已知 PFAS 暴露量较高的社区和群体（例如白血病）中，横纹肌肉瘤、淋巴瘤以及脑癌、中枢神经系统癌、肾癌、睾丸癌和甲状腺癌。我们将利用两项现有的加州儿童癌症研究和互补设计，提供大量具有居住信息以及接触血液和灰尘的儿童癌症病例和对照的数量子集的样本。 PFAS 水暴露评估，我们将使用贝叶斯药代动力学校准将测量的饮用水浓度与测量的血清生物标志物相结合的方法，以提供改进了暴露估计。我们还将结合靶向和非靶向质谱策略来测量血液和灰尘样本中的 PFAS。这三个研究目标之间将产生协同作用重叠研究参与者（目标 1 和 2）、协调实验室分析（目标 2 和 3）和统计分析（目标 1、2、3），并特别关注白血病——最常见的儿童癌症（目标 1、2、3）。 ViCTER 联盟将得到行政和科学监督核心的支持，以协调和整合三个研究目标的资源和活动。凭借我们独特的资源、新颖的方法和补充专业知识，该提案满足了评估人口的迫切需要与 PFAS 有关的儿童癌症风险。