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: 7482294
• 负责人: Craig M Steinmaus
• 金额: $ 38.61万
• 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/7482294
• 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; Range; Regulation; Relative Risks; Risk; Risk Assessment; Role; Sampling; Source; Standards of Weights and Measures; Subgroup; System; Time; Urine; Water; animal data; base; cancer risk; carcinogenesis; carcinogenicity; design; drinking water; early childhood; environmental agent; environmental carcinogenesis; epidemiology study; 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）：我们来自智利北部的新生态证据表明，儿童期或子宫内接触砷可能导致年轻人肺癌发病率增加 10 倍。这可能是第一次将生命早期接触常见环境因素与人类成人患癌症的高风险联系起来。尽管得到了有趣的动物数据的支持，但这些发现是初步的，需要得到证实。智利北部高度独特的砷暴露情景为实现这一目标提供了绝佳且难得的机会。由于智利北部几乎每个人都从大型市政水源获取水，并且所有这些水源过去的砷含量在过去 50 年或更长时间里都有详细记录，因此可以使用过去暴露的数据来研究砷的致癌性，这些数据比可以在世界其他任何地方获得。此外，该地区长达 14 年的高暴露期导致数万人仅在子宫内和幼儿期就受到高暴露。因此，该领域提供了一个独特的机会，通过过去接触的良好数据来研究早期致癌物的长期影响。我们建议使用涉及所有当地病理学家的快速病例确定系统对三年内获得的 675 例肺癌和膀胱癌病例进行病例对照研究。控制权将从智利选民登记册中获得，其中包括 94% 的智利人口。我们将获得包含过去暴露数据的剂量反应信息，该信息比之前任何研究都更准确，并且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，并调查与代谢、饮食、遗传和其他因素相关的易感性。我们发现证据表明，单甲基化砷 (MMA) 水平较高的人患癌症的风险可能比其他人高 2-5 倍。这是否是由于很少研究但剧毒的三价形式（MMA3）所致，我们将对此进行探索，并可以提供有关砷致癌的主要有毒物质的新信息。美国有数百万人接触饮用水中的砷。尽管这些群体的癌症风险可能极高，但目前的美国砷法规并未纳入有关潜在易感亚群体的信息。从该项目中获得的信息可能有助于确定某些人，例如儿童、孕妇、砷代谢不良的人或营养不良的人，在制定监管标准时是否需要特别考虑。作为该项目的一部分，我们将计划提供有关生命早期暴露、MMA3、饮食以及未来遗传和蛋白质组学研究的信息，这些信息可以进一步深入了解环境致癌的重要辅助因素和机制。