Project 1: Exposomics and Arsenic Epidemiology

项目1：暴露组学和砷流行病学

• 批准号: 9260363
• 负责人: Craig M Steinmaus
• 金额: $ 22.82万
• 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/9260363
• 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; Environmental Tobacco Smoke; Epidemiology; Ethnic Origin; Genetic; Glucocorticoids; Glycosylated hemoglobin A; Goals; Gonadal Steroid Hormones; Habits; Hazardous Substances; Health; Hormones; Hypertension; In Vitro; Incidence; Individual; 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; 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; Workplace; biological adaptation to stress; cohort; design; disease mechanisms study; disorder risk; drinking; drinking water; early life exposure; environmental stressor; fatty acid metabolism; improved; indexing; insight; lifestyle factors; low socioeconomic status; mortality; novel; respiratory; sex; social; 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：总结/摘要 暴露组的概念不仅涉及多种化学物质的综合影响，还涉及社会影响 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。美国数百万人接触砷，砷在超级基金中排名第一 化学品优先清单。由于多种原因，智利北部是世界上研究砷的最佳地点之一。 首先，这里是地球上最干旱的适宜居住的地方，尽管人口众多，但单独的水却很少 基本上每个城市都由自己的单一市政来源供电。二、这些来源 砷浓度范围很广，所有这些来源的砷记录均可用于 超过50年。因此，人们只需要知道一个人在哪几年居住在哪些城市 了解该人一生的砷暴露情况。这种类型的终生暴露数据并不 可以在包括美国在内的世界任何其他地区使用。第三，该地区最大的城市安托法加斯塔 1958 年开始的明显高砷时期，当时两条砷浓度高的河流被 转移到城市饮用，并于 1970 年安装砷处理厂后结束。学习中 现在对在这个独特的暴露时期出生的人的健康影响提供了一个难得的机会 检查生命早期接触对成人疾病的影响。超级基金一直支持这方面的研究 20多年来，我们取得了大量新发现。我们发现生命早期的砷 暴露与成人肺癌显着增加 >5 倍、膀胱癌显着增加 >7 倍相关 癌症和呼吸道影响与大量吸烟相似。我们还发现了明显的增长 由于砷代谢、遗传以及常见的共同暴露（如二手烟和二手烟）而易感 工作场所暴露。最近，我们发现与砷相关的癌症和肺部疾病的发病率要高得多 超重人群（例如协同指数=4.05，95%CI=1.27–12.88）。在这里，我们建议使用 智利独特的暴露场景探索砷与高血压和内分泌之间的关联 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。然而迄今为止，还没有研究使用终生暴露信息对它们进行检验，也没有研究 研究调查了早期生活暴露、肥胖或压力的潜在改变影响。这很重要 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。 总的来说，我们项目的意义在于砷暴露在美国很普遍，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。这也在于 肥胖和压力是疾病常见且重要的危险因素，但目前对此知之甚少。 了解生命早期暴露的长期影响。我们的目标是提供有关这些的新信息 可能对美国砷和其他化学品暴露政策产生重要影响的问题。