Project 3: Arsenic Biomarker Epidemiology

在美国和全世界，数百万人暴露在砷污染的水中，砷是 在最新的超级基金网站有害物质优先列表中排名第一。目前的证据 表明肺癌是砷相关死亡率的主要原因。此外，砷还 增加了非恶性肺病的发病率，并获得了有趣的初步证据 我们的研究小组的研究表明，那些在幼儿时期或在子宫内暴露的人， 易受砷的恶性和非恶性肺部影响。我们提出了一系列 进一步探讨儿童期砷暴露的影响以及可能 赋予对这些效应的敏感性。拟议的流行病学研究包括一项病例对照研究， 北方地区儿童期和宫内砷暴露与青年人肺癌风险 智利，以及肺功能和呼吸系统健康与砷暴露的横断面研究， 西孟加拉的孩子们。此外，在这些研究中收集的生物样品， 从我们过去的几项研究中收集的样本将用于对砷的进一步调查 敏感性和毒性机制包括：1）。与个体差异有关的易感性 尿中MMA 3浓度，一种高毒性但很少研究的砷代谢物; 2）。易感性 与遗传多态性相关，特别是涉及AS 3 MT（cyt 19）、GSTO 1、GSTM 1和 EGFR对3）。尿蛋白质组学模式作为暴露、疾病和 易感性在过去的几年里，超级基金提供了核心资金，使我们能够使许多 对砷的研究做出了新的重要贡献。我们的目标是延续这一成功模式，但 新的重点是儿童期和子宫内暴露对呼吸系统的影响以及相关的 毒性和易感性的机制。考虑到美国人摄入砷的普遍性 和世界范围内，以及非常高的风险，肺部疾病后，早期的生活暴露，我们已经看到，在我们的 初步研究，调查这些影响有可能产生重要的新的公共卫生， 关于有毒物质在子宫内和儿童期影响的科学信息。

Millions of people are exposed to arsenic-contaminated water in the U.S. and worldwide, and arsenic is ranked first on the most recent priority list of Superfund site hazardous substances. Current evidence suggests that lung cancer is the leading cause of arsenic-associated mortality. In addition, arsenic also increases the incidence of non-malignant pulmonary disease, and intriguing preliminary evidence obtained by our research group suggests that those exposed as young children or in utero are particularly susceptible to both the malignant and non-malignant pulmonary effects of arsenic. We propose a series of investigations to further explore the effects of childhood arsenic exposure and the mechanisms that may confer susceptibility to these effects. The proposed epidemiological studies include a case-control study of childhood and in utero arsenic exposure and subsequent risks of lung cancer in young adults in Northern Chile, and a cross-sectional study of lung function and respiratory health and arsenic exposure involving children in West Bengal. In addition, biological samples collected during these studies, combined with samples collected from several of our past studies, will be used for additional investigations on arsenic susceptibility and mechanisms of toxicity including: 1). Susceptibility related to individual differences in urinary concentrations of MMA3, a highly toxic but rarely studied arsenic metabolite; 2). Susceptibility related to genetic polymorphisms, in particular those involving AS3MT (cyt19), GSTO1, GSTM1, and EGFR. 3). Assessment of urinary proteomic patterns as biomarkers of exposure, disease, and susceptibility. In past years, Superfund has provided the core funding that has allowed us to make many new and important contributions to research on arsenic. Our goal is to continue this successful model, but with a new focus on the respiratory effects of childhood and in utero exposures and the associated mechanisms of toxicity and susceptibility. Given the widespread exposure to ingested arsenic in the U.S. and worldwide, and the very high risks of lung disease following early life exposures we have seen in our preliminary studies, investigating these effects has the potential to yield important new public health and scientific information regarding the in utero and childhood effects of toxic substances.