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

描述(申请人提供)：智利第二区的早期生活砷暴露和成人死亡率美国和世界各地的数百万人暴露在饮用水中高浓度的砷中，与这些暴露相关的癌症、心血管疾病和其他不良后果的估计风险非常高。从1958年到1970年，智利第二区的安托法加斯塔市有超过125,000人经历了一段突如其来和不寻常的饮用水高砷浓度时期。这一暴露期非常独特，在1958年首次使用高污染饮用水水源之前暴露量很低，1971年安装除砷厂时，水中砷浓度突然下降(从约870 5g/L降至最终的10 5g/L)。据我们所知，在如此庞大且一致暴露的人口中，这样的情况从未报告过任何环境污染物。我们对这一独特种群的调查已经取得了很高的成果。例如，我们发现，在高暴露期间，安托法加斯塔儿童或子宫内儿童的死亡率大幅上升。这些增加出现在膀胱癌(标准化死亡率[SMR]=21.3；95%可信区间[CI]11.6至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)。非癌症死亡增加的原因是：支气管扩张(SMR=25.1；95%CI，13.4至42.9)、急性心肌梗死(SMR=2.4；95%CI，1.9至3.0)和慢性肾脏疾病(SMR=2.3；95%CI，1.6至3.3)。在膀胱癌(SMR=55.9；95%CI，25.5至106)和支气管扩张(SMR=46.2；95%CI，21.1至87.7)的高暴露时期出生的人(可能在子宫内暴露)的发病率上升幅度最大。这是第一项将早期接触一种常见饮用水污染物与成人患癌症和非癌症结果的高风险联系起来的人类研究。由于高暴露时期(1958-1970年)的时机，我们之前的研究只能评估早期生活暴露对相对年轻的成年人(即30多岁和40多岁的人)的长期影响。在这项提案中，我们寻求将我们的调查范围扩大到2001-2010年间另外十年的死亡数据。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延续到老年群体。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更高。由于这些较高的基线风险，这些老年群体中因砷而导致的相对风险增加将导致更多与砷相关的死亡，从而使暴露人群的总体疾病负担增加更多。目前，许多美国人使用的私人水井含有高浓度的砷，包括一些与安托法加斯塔一样高或更高的水井。智利的第二区域提供了世界上最好的人口来评估早期生活中砷暴露的影响。原因包括这里是地球上最干燥的有人居住的地方，每个城镇只有一个水源，而且过去50年或更长时间里砷浓度的准确记录。有限的水源数量和良好的记录意味着，可以比世界其他任何地方更准确地评估来自遥远过去的砷暴露。这种关于暴露的准确数据大大减少了许多生态研究中常见的暴露评估问题(即生态谬误)。另一个优势是，在安托法加斯塔高度接触砷的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，生态研究设计是理想的，因为它允许我们在一个非常大的暴露人群中研究各种不同的死亡原因，具有关于过去暴露的良好数据，良好的统计能力，以及较低的重大混淆概率。这项死亡率研究可能是唯一可用的机会，以了解早年接触砷对年轻人多种死因的主要影响是否会延续到老年群体。这将对公共卫生产生几个重要的影响。例如，美国和世界各地的医疗保健提供者需要更多地警惕砷对健康的影响和暴露，特别是在孕妇、婴儿和幼儿中，并应该询问所有来自农村地区的患者是否有私人水井，以及他们是否接受过砷测试。此外，目前的饮用水标准10 5g/L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早年接触有关的风险。 与公共健康相关：饮用水中的砷暴露是世界各地普遍存在的健康危害，包括美国在内，在美国，数百万人饮用经常被砷污染的私人水井的水。到目前为止，我们在智利的死亡率研究中表明，母亲在怀孕期间及其子女的暴露会导致年轻人死亡率的大幅增加。由于这是任何早期生命暴露后已知的最高风险，我们认为至关重要的是将这项死亡率研究再继续十年，以更充分地确定长期影响的程度。

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. PUBLIC HEALTH RELEVANCE: Arsenic exposure from drinking water is a widespread health hazard throughout the world, including the United States where millions of people drink water from private wells which are quite often contaminated with arsenic. We have shown so far in our mortality study in Chile, the exposure of mothers during pregnancy, and of their children, results in major increase in mortality in young adults. Since this is the highest known risk after any early life exposure, we think it is critically important to continue this mortality study a further ten years to more fully ascertain the magnitude of the long term effects.