Incident cancer studies in a unique arsenic-exposed area of Chile

智利独特的砷暴露地区的癌症事件研究

• 批准号: 7628964
• 负责人: Craig M Steinmaus
• 金额: $ 39.31万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-09 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7628964
• 关键词: Adult; Animal Model; Animals; Area; Arsenic; Biological; Blood specimen; Carcinogens; Case-Control Studies; Child; Childhood; Chile; Data; Diet; Dietary Factors; Disease; Disease susceptibility; Dose; Epidemiologic Studies; Exposure to; Future; Genetic; Genomics; Health Policy; High-Risk Cancer; Human; Individual Differences; Knowledge; Life; Link; Longitudinal Studies; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of urinary bladder; Metabolism; Other Genetics; Outcome; Pathologist; Play; Population; Predisposition; Pregnant Women; Proteomics; Public Health; Regulation; Relative Risks; Risk; Risk Assessment; Role; Sampling; Source; Subgroup; System; Time; Urine; Water; animal data; base; cancer risk; carcinogenesis; carcinogenicity; design; drinking water; early childhood; environmental agent; environmental carcinogenesis; epidemiology study; high risk; in utero; insight; metabolic abnormality assessment; monomethylarsonous acid; nutrition; response; young adult

DESCRIPTION (provided by applicant): Our new ecologic evidence from Northern Chile suggests that arsenic exposure in childhood or in utero could cause up to a 10-fold increase in lung cancer in young adults. This may be the first time that early-life exposure to a common environmental agent has been linked to such high risks of an adult cancer in humans. Although supported by intriguing animal data, these findings are preliminary and need to be confirmed. The highly unique arsenic exposure scenario in Northern Chile offers an excellent and rare opportunity to do this. Because almost everyone in Northern Chile obtains their water from large municipal sources, and past arsenic levels in all of these sources are well documented over the past 50 years or more, arsenic carcinogenicity can be studied using data on past exposure that are much more accurate than can be obtained anywhere else in the world. In addition, a very distinct 14-year period of high exposure in this area has created a population where tens of thousands of people were highly exposed only in utero and early childhood. As such, this area provides a unique opportunity to study the long-term impacts of an early-life carcinogen with excellent data on past exposure. We propose a case-control study of 675 lung and bladder cancer cases obtained over a three-year period using a rapid case ascertainment system involving all local pathologists. Controls will be obtained from the Chile electoral register which includes 94% of the Chile population. We will obtain dose-response information with data on past exposure that is more accurate than found in any previous study and that can be directly applied to US regulatory and public health decisions. Biological samples will be collected and susceptibility related to metabolism, diet, genetics, and other factors will also be investigated. We have found evidence that people producing high levels of monomethylated arsenic (MMA) may have 2-5 times higher cancer risks than others. Whether this is due to the rarely studied but highly toxic trivalent form (MMA3) will be explored and could provide new information on the primary toxic species of arsenic carcinogenesis. Millions of people in the US are exposed to drinking water arsenic. Current US arsenic regulations do not incorporate information on potentially susceptible subgroups despite the fact that cancer risks in these groups could be exceedingly high. The information gained from this project may help to determine if some people, such as children, pregnant women, those who metabolize arsenic poorly, or those with poor nutrition, may need special consideration in regulatory standard setting. Information on early-life exposure, MMA3, diet, and the future genetic and proteomic studies we will plan as part of this project could add further insight into the important co-factors and mechanisms of environmental carcinogenesis.

描述（由申请人提供）：我们来自智利北方的新生态证据表明，儿童期或子宫内的砷暴露可导致年轻成人肺癌增加10倍。这可能是第一次将早期接触常见环境因子与人类患成人癌症的高风险联系起来。虽然有有趣的动物数据支持，但这些发现是初步的，需要得到证实。智利北方高度独特的砷暴露情景为这样做提供了一个绝佳而难得的机会。由于智利北方几乎每个人都从大型城市水源中获得水，并且在过去50年或更长时间内，所有这些水源中过去的砷含量都有很好的记录，因此可以使用比世界其他地方更准确的过去暴露数据来研究砷的致癌性。此外，这一地区14年的高暴露期非常明显，使成千上万的人仅在子宫内和幼儿期就受到高暴露。因此，这一领域提供了一个独特的机会，研究早期生活致癌物的长期影响，并提供了关于过去暴露的良好数据。我们提出了一个病例对照研究，675例肺癌和膀胱癌病例获得了三年的时间内使用快速的情况下确定系统，涉及所有当地的病理学家。控制将从智利选民登记册中获得，其中包括智利94%的人口。我们将获得剂量-反应信息，其中包括过去暴露的数据，这些数据比以往任何研究都更准确，可以直接应用于美国监管和公共卫生决策。将收集生物样本，并研究与代谢、饮食、遗传和其他因素相关的易感性。我们已经发现证据表明，产生高水平单甲基砷（MMA）的人可能比其他人的癌症风险高2-5倍。这是否是由于很少研究，但高毒性的三价形式（MMA 3）将被探讨，并可能提供新的信息的主要有毒物种的砷致癌作用。美国有数百万人暴露于饮用水砷。目前美国砷法规没有纳入潜在易感亚组的信息，尽管这些群体的癌症风险可能非常高。从该项目中获得的信息可能有助于确定某些人，如儿童，孕妇，砷代谢不良或营养不良的人，在制定监管标准时是否需要特别考虑。关于早期生活暴露，MMA 3，饮食以及未来遗传和蛋白质组学研究的信息，我们将计划作为该项目的一部分，可以进一步了解环境致癌的重要辅助因素和机制。