Project 1: Exposomics and Arsenic Epidemiology

项目1：暴露组学和砷流行病学

• 批准号: 9919581
• 负责人: Craig M Steinmaus
• 金额: $ 22.56万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9919581
• 关键词: Acute myocardial infarction; Address; Adult; Affect; Animals; Anxiety; Area; Arsenic; Biological Markers; Blood Pressure; Blood specimen; Cardiovascular Diseases; Case-Control Studies; Chemical Exposure; Chemicals; Chile; Chronic Kidney Failure; Cities; Communities; Data; Diabetes Mellitus; Diagnosis; Diet; Disease; Endocrine; Endocrine System Diseases; Environment; Epidemiology; Ethnic Origin; Exposure to; Genetic; Glucocorticoids; Glycosylated hemoglobin A; Goals; Gonadal Steroid Hormones; Habits; Hazardous Substances; Health; Hormones; Hypertension; In Vitro; Incidence; Individual; Ingestion; Investigation; Lead; Life; Link; Long-Term Effects; Lung diseases; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of pancreas; Malignant neoplasm of prostate; Malignant neoplasm of urinary bladder; Mental Depression; Metabolic Pathway; Metabolism; Minority; Molecular; Morbidity - disease rate; Municipalities; Neurological outcome; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Occupational Exposure; Odds Ratio; Outcome; Overweight; Persons; Pharmaceutical Preparations; Physicians; Planet Earth; Plants; Play; Poison; Policies; Population; Predisposition; Prevalence; Records; Regulation; Renal Cell Carcinoma; Research; Research Support; Risk; Risk Assessment; Risk Factors; Rivers; Role; Rural Community; Sampling; Serum; Signal Recognition Particle; Smoking; Source; Stress; Superfund; Taiwan; Toxic effect; Tuberculosis; Uterine Cancer; Water; biological adaptation to stress; cohort; design; disease mechanisms study; disorder risk; drinking; drinking water; early life exposure; environmental stressor; environmental tobacco smoke; fatty acid metabolism; hypothalamic-pituitary-adrenal axis; improved; indexing; insight; lifestyle factors; low socioeconomic status; mortality; mortality risk; novel; perceived stress; respiratory; sex; social factors; superfund chemical; synergism; tumor; water quality

PROJECT 1: SUMMARY/ABSTRACT The concept of the exposome involves not only the combined effects of multiple chemicals, it entails the social and lifestyle factors that influence chemical toxicity, and the idea that the specific life stage of exposure can affect disease risks. Millions of people in the US are exposed to arsenic, which is ranked first on the Superfund chemical priority list. For several reasons, northern Chile is one of the best places in the world to study arsenic. First, this is the driest habitable place on earth, and despite its large population, it has very few individual water sources, with essentially each city being supplied by its own single municipal source. Second, these sources have had a wide range of arsenic concentrations, and arsenic records on all of these sources are available for over 50 years. Because of this, one simply needs to know what cities a person has lived in during which years to have a good idea of that person's lifetime arsenic exposure. This type of lifelong exposure data is not available in any other area in the world including the US. Third, the largest city in the area, Antofagasta, had a distinct period of high exposure beginning in 1958 when two rivers with high arsenic concentrations were diverted to the city for drinking, and ending in 1970 when an arsenic treatment plant was installed. Studying health effects now in people who were born during this distinct exposure period offers a rare opportunity to examine the impacts of early-life exposure on adult disease. Superfund has been supporting research in this area for 20+ years, and we have made a large number of novel discoveries. We found that early-life arsenic exposure was associated with >5-fold significant increases in adult lung cancer, >7-fold increases in bladder cancer, and respiratory effects similar to those seen with heavy smoking. We also identified marked increases in susceptibility due to arsenic metabolism, genetics, and common co-exposures like second-hand smoke and workplace exposures. Most recently, we found that arsenic-related cancer and lung disease were much greater in people who were overweight (e.g. synergy index=4.05, 95%CI=1.27–12.88). Here, we propose to use the unique exposure scenario in Chile to explore associations between arsenic and hypertension and endocrine diseases like prostate cancer and diabetes. Currently, data linking these outcomes to arsenic are mixed or controversial. However to date, no study has examined them using information on lifetime exposure, and no study has examined the potential modifying effects of early-life exposure, obesity, or stress. This is important since our recent research suggests that each of these factors may play a major role in arsenic-related disease. Overall, the significance of our project lies in the facts that arsenic exposure in the US is widespread, and that diabetes, hypertension, and prostate cancer are major causes of morbidity and mortality here. It is also lies in the facts that obesity and stress are common and important risk factors for disease, and that little is currently known about the long-term effects of early-life exposure. Our goal is to provide new information on these issues that could have important implications for US policies on arsenic and other chemical exposures.

项目1：摘要/摘要 曝光体的概念不仅涉及多种化学物质的综合作用，它还涉及到社会 以及影响化学毒性的生活方式因素，以及接触的特定生命阶段可以 影响疾病风险。美国数百万人暴露在砷中，这在超级基金中排名第一 化学品优先列表。出于几个原因，智利北部是世界上研究砷的最佳地点之一。 首先，这是地球上最干燥的宜居之地，尽管人口众多，但单项水资源却很少。 来源，基本上每个城市由其自己的单一市政来源供应。第二，这些消息来源 有很大范围的砷浓度，所有这些来源的砷记录都可以 50多年了。正因为如此，人们只需要知道一个人在哪些城市生活了哪些年 对此人一生接触砷的情况有一个好的了解。这种类型的终身暴露数据不是 在世界上任何其他地区都可以买到，包括美国。第三，该地区最大的城市安托法加斯塔有一个 从1958年开始的明显的高暴露时期，当时两条高砷浓度的河流 被转移到城市饮用，并于1970年结束，当时安装了一个砷处理厂。学习 现在对出生在这一不同暴露时期的人的健康影响提供了一个难得的机会 研究早期接触对成人疾病的影响。超级基金一直在支持这方面的研究 20多年来，我们有了大量的新奇发现。我们发现早期生命中的砷 暴露与成人肺癌显著增加5倍，膀胱癌增加7倍相关 癌症，以及与重度吸烟相似的呼吸影响。我们也发现了显著的增长 由于砷代谢、遗传以及二手烟和二手烟等常见联合暴露而导致的易感性 工作场所的暴露。最近，我们发现与砷相关的癌症和肺部疾病要严重得多。 在超重人群中(如协同指数=4.05，95%CI=1.27~12.88)。在这里，我们建议使用 智利独特的暴露情景以探索砷与高血压和内分泌之间的关系 前列腺癌和糖尿病等疾病。目前，将这些结果与砷联系起来的数据是混合的或 有争议的。然而，到目前为止，还没有研究使用关于终身接触的信息来检查他们，也没有 一项研究调查了早年暴露、肥胖或压力的潜在调整效果。这事很重要 因为我们最近的研究表明，这些因素中的每一个都可能在砷相关疾病中发挥重要作用。 总体而言，我们项目的意义在于这样一个事实，即美国接触砷的情况很普遍，而且 糖尿病、高血压和前列腺癌是这里发病率和死亡率的主要原因。它还在于 肥胖和压力是疾病的常见和重要风险因素，而目前这一事实很少 知道早年暴露的长期影响。我们的目标是提供有关这些方面的新信息 这些问题可能会对美国关于砷和其他化学物质暴露的政策产生重要影响。