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

项目总结/摘要 全氟烷基和多氟烷基物质（PFAS）已用于许多制造和商业产品中 近几十年来，尽管逐步淘汰了早期的 例如PFOS和PFOA。PFAS暴露于人类的途径因年龄而异; 婴儿和儿童通常来自母乳喂养和摄入沉降的灰尘，青少年和成年人 主要通过食物和水接触。PFAS与几种不良健康结果有关， 包括成年人的癌症尽管有几份关于PFAS污染地区儿童癌症集群的报告， 儿童的身体负担可能比成人高，没有研究系统地评估 儿童癌症风险，部分原因是儿童癌症相对罕见。我们建议进行第一次 PFAS和儿童癌症的研究，通过整合来自四个机构的研究人员的专业知识， 一个跨学科的虚拟联盟，在儿科和癌症流行病学和环境方面拥有专业知识， 工程和健康科学。使用创新的方法，这个虚拟联盟将表征PFAS 通过检查饮用水（目标1）、新生儿和妊娠中的全氟辛烷磺酸， 血液样本（目标2）和家庭灰尘（目标3），从怀孕到 幼儿期以及随后患儿童癌症的风险。我们将重点关注癌症， 先前在已知高暴露于PFAS的社区和群体中报告，如白血病， 横纹肌肉瘤、淋巴瘤和脑癌、中枢神经系统癌、肾癌、睾丸癌和甲状腺癌。 我们将利用现有的两项加州儿童癌症研究，并采用互补设计， 儿童癌症病例数和有住所信息、可获得血液和灰尘的对照数 样本的子集。PFAS水暴露评估，我们将使用贝叶斯药代动力学校准 一种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， 改进暴露估计。我们还将结合联合收割机靶向和非靶向质谱策略， 测量血液和灰尘样本中的PFAS。这三个研究目标之间将有协同作用， 重叠研究受试者（目的1和2），协调实验室分析（目的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， 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， 方法和互补的专门知识，这项建议响应了评估人口的迫切需要， 与PFAS有关的儿童癌症风险。

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.