Early-life arsenic exposure and adult mortality in Region II, Chile

智利第二区的生命早期砷暴露和成人死亡率

• 批准号: 8329608
• 负责人: ALLAN H SMITH
• 金额: $ 24.33万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-07 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8329608
• 关键词: Acute myocardial infarction; Adult; Arsenic; Birth Certificates; Birth Place; Bladder; Bronchiectasis; Cardiovascular Diseases; Cause of Death; Cessation of life; Child; Childhood; Chile; Chronic Disease; Chronic Kidney Failure; Chronic Obstructive Airway Disease; Cities; Confidence Intervals; Data; Disease; Distant; Drops; Environmental Exposure; Environmental Pollution; Excision; Exposure to; Goals; Health; Health Hazards; Health Personnel; High-Risk Cancer; Individual; Infant; Investigation; Kidney; Knowledge; Larynx; Life; Link; Liver; Long-Term Effects; Malignant Neoplasms; Malignant neoplasm of larynx; Malignant neoplasm of liver; Malignant neoplasm of lung; Malignant neoplasm of urinary bladder; Measurement; Medical Records; Methods; Mothers; Myocardial Ischemia; Non-Malignant; Outcome; Pathology Report; Patients; Pattern; Perinatal Exposure; Persons; Plants; Population; Pregnancy; Pregnant Women; Probability; Public Health; Publishing; Radiology Specialty; Records; Relative Risks; Renal carcinoma; Reporting; Research Design; Rest; Risk; Risk Estimate; Source; Testing; Time; United States; Water; Water Supply; Work; adverse outcome; age group; aged; base; burden of illness; cancer risk; drinking water; early life exposure; experience; human study; in utero; mortality; rural area; young adult

DESCRIPTION (provided by applicant): Early life arsenic exposure and adult mortality in Region II, Chile Millions of people in the US and worldwide are exposed to high concentrations of arsenic in their drinking water, and the estimated risks of cancer, cardiovascular disease, and other adverse outcomes associated with these exposures is very high. From 1958 to 1970, over 125,000 people in the city of Antofagasta in Region II of Chile experienced a sudden and unusual period of high drinking water arsenic concentrations. This exposure period was highly distinct, with low exposure before the highly contaminated drinking water sources were first used in 1958, and a sudden drop in water arsenic concentrations (from around 870 5g/L to eventually 10 5g/L) when an arsenic removal plant was installed in 1971. As far as we know, a scenario like this, in such a large and uniformly exposed population, has never been reported for any environmental contaminant. Our investigation of this unique population has already been highly productive. For example, we identified major increases in mortality in Antofagasta among people who were young children or in utero during the high exposure period. These increases were found for bladder cancer (standardized mortality ratio [SMR]=21.3; 95% confidence interval [CI], 11.6 to 35.7), laryngeal cancer (SMR=10.5; 95% CI, 3.4 to 24.6), lung cancer (SMR=6.8; 95% CI, 5.4 to 8.4), kidney cancer (SMR=3.4; 95% CI, 1.7 to 6.2) and liver cancer (SMR=3.1; 95% CI, 1.8 to 4.9). Non-cancer deaths were increased from bronchiectasis (SMR=25.1; 95% CI, 13.4 to 42.9), acute myocardial infarction (SMR=2.4; 95% CI, 1.9 to 3.0) and chronic renal disease (SMR=2.3; 95% CI, 1.6 to 3.3). Increases were greatest for those born during the high exposure period (with likely in utero exposure) for bladder cancer (SMR=55.9; 95%CI, 25.5 to 106) and bronchiectasis (SMR=46.2; 95%CI, 21.1 to 87.7). This was the first human study to link early life exposure to a common drinking water contaminant to high risks of cancer and non-cancer outcomes in adults. Because of the timing of the high exposure period (1958-1970), our previous studies could only assess the long-term effects of early life exposure in relatively young adults (i.e., those in their 30s and 40s). In this proposal, we seek to extend our investigation to cover ten additional years of mortality data, from 2001-2010. This will allow us to evaluate whether the effects of early life exposure we identified in young adults continue into older age groups. This is important because the baseline risks for most chronic diseases are higher in these older age groups. Because of these higher baseline risks, increases in relative risk due to arsenic in these older groups would cause larger numbers of arsenic-related deaths, and therefore larger increases in the overall burden of disease in exposed populations. Currently, many people in the US use private wells with high concentrations of arsenic, including some as high or higher than they were in Antofagasta. Region II of Chile provides the best population in the world to assess the effects of early life arsenic exposure. The reasons include the fact that this is the driest inhabited place on earth, with only one water source for each town and city and accurate records of arsenic concentrations for the last 50 years or more. The limited number of water sources and availability of good records means that arsenic exposure from the distant past can be assessed with greater accuracy than can be done anywhere else in the world. This accurate data on exposure substantially reduces the exposure assessment problems (i.e., ecologic fallacy) commonly seen in many ecologic studies. Another advantage is that the number of people who were highly exposed in Antofagasta is more than ten times greater than in any other published arsenic study in the world. In this situation, the ecologic study design is ideal, since it allows us to study a variety of different causes of death, in a very large exposed population, with good data on past exposure, good statistical power, and a low probability of major confounding. This mortality study is probably the only opportunity available to see if the already identified major effects of early life exposure to arsenic on multiple causes of death in young adults continues into older age groups. This would have several important public health implications. For example, health care providers in the US and worldwide would need to be more alert to arsenic health effects and exposure, especially in pregnant women, infants, and young children, and should ask all patients from rural areas if they have private wells, and if they have been tested for arsenic. In addition, the current drinking water standard of 10 5g/L might need further examination, since the risk estimates on which this standard is based did not consider the risks associated with early life exposure.

描述（由申请人提供）：智利第二区的早期砷暴露和成人死亡率美国和世界各地数百万人暴露于饮用水中的高浓度砷，估计患癌症、心血管疾病和与这些暴露相关的其他不良后果的风险非常高。从1958年到1970年，智利第二区安托法加斯塔市的125，000多人经历了一段突然而不寻常的高饮用水砷浓度时期。这个暴露期是非常明显的，在1958年首次使用高度污染的饮用水源之前，暴露水平较低，1971年安装除砷厂时，水砷浓度突然下降（从870 5g/L左右降至10 5g/L）。据我们所知，在如此庞大和均匀暴露的人群中，从未有任何环境污染物报告过这种情况。我们对这一独特群体的调查已经取得了很高的成果。例如，我们发现在安托法加斯塔，在高暴露期内，幼儿或子宫内的人的死亡率大幅增加。这些增加被发现为膀胱癌（标准化死亡率[SMR]=21.3; 95%置信区间[CI]，11.6 - 35.7），喉癌（SMR=10.5; 95% CI，3.4至24.6）、肺癌（SMR=6.8; 95% CI，5.4至8.4）、肾癌（SMR=3.4; 95% CI，1.7至6.2）和肝癌（SMR=3.1; 95% CI，1.8至4.9）。支气管扩张（SMR=25.1; 95% CI，13.4 - 42.9）、急性心肌梗死（SMR=2.4; 95% CI，1.9 - 3.0）和慢性肾脏疾病（SMR=2.3; 95% CI，1.6 - 3.3）导致的非癌症死亡增加。在膀胱癌（SMR=55.9; 95%CI，25.5 - 106）和支气管扩张症（SMR=46.2; 95%CI，21.1 - 87.7）高暴露期出生的婴儿（可能在子宫内暴露）增加最多。这是第一项将早期生活暴露于常见饮用水污染物与成年人患癌症和非癌症结果的高风险联系起来的人类研究。由于高暴露期（1958-1970年）的时间，我们以前的研究只能评估相对年轻的成年人早期生活暴露的长期影响（即，30多岁和40多岁的人）。在本提案中，我们寻求扩大调查范围，以涵盖2001-2010年另外十年的死亡率数据。这将使我们能够评估我们在年轻人中发现的早期生活暴露的影响是否会持续到老年组。这一点很重要，因为大多数慢性病的基线风险在这些老年群体中较高。由于这些较高的基线风险，在这些老年群体中由于砷引起的相对风险增加将导致更多的砷相关死亡，因此暴露人群的总体疾病负担将更大幅度增加。目前，美国许多人使用的私人威尔斯井砷浓度很高，其中一些井的砷浓度与安托法加斯塔一样高或更高。智利的第二区提供了世界上最好的人口来评估生命早期砷暴露的影响。原因包括这是地球上最干燥的有人居住的地方，每个城镇和城市只有一个水源，以及过去50多年来砷浓度的准确记录。有限的水源和良好记录的可用性意味着可以比世界上其他任何地方更准确地评估遥远过去的砷暴露。这一准确的接触数据大大减少了接触评估问题（即，生态谬误）常见于许多生态研究。另一个优势是，安托法加斯塔的高暴露人数是世界上任何其他已发表的砷研究的十倍以上。在这种情况下，生态学研究设计是理想的，因为它允许我们在非常大的暴露人群中研究各种不同的死亡原因，具有良好的既往暴露数据，良好的统计功效，以及低概率的主要混杂因素。这项死亡率研究可能是唯一的机会，看看已经确定的早期生活暴露于砷对年轻人多种死亡原因的主要影响是否会持续到老年组。这将对公共卫生产生若干重要影响。例如，美国和世界各地的卫生保健提供者需要更加警惕砷对健康的影响和暴露，特别是孕妇、婴儿和幼儿，并应询问所有来自农村地区的患者是否有私人威尔斯井，以及他们是否接受过砷检测。此外，目前的饮用水标准10 - 5克/升可能需要进一步审查，因为该标准所依据的风险估计没有考虑与生命早期接触有关的风险。