California Nevada Arsenic and Lung Cancer Study

描述(申请人提供)：数百万人接触到饮酒 被砷污染的水，以及广泛的流行病学证据 证明了这些暴露会导致癌症。事实上，在高处 浓度的风险水平超过任何其他已知的环境 致癌物质。在相对较低的暴露下，如在 美国，终身接触癌症的风险可能超过千分之一，甚至 在新提出的10微克/升的饮用水标准中， 易感人群，如吸烟或饮食不佳的人， 风险可能会更大。此外，我们在智利的研究表明 对于饮用被砷污染的水的人来说，风险尤其高，因为 孩子们。不幸的是，低暴露下的癌症风险是不确定的，因为风险 迄今为止的估计包括从高剂量水平到低剂量水平的外推 剂量-反应关系形状未知的暴露。是这样的 外推极具争议性。因此，我们建议一项 以人群为基础的病例对照研究评估肺癌的相关性 饮用水中的砷含量处于低至中等水平。现有证据 表明肺癌可能是导致更多因摄入而死亡的原因 砷比包括膀胱癌在内的所有其他癌症部位的总和还要多。它是 因此，对剂量反应有一个清晰的了解尤为重要 这种癌症的关系。研究区域包括加利福尼亚州的金斯县， 以及内华达州的六个县。这些县是人口最多的县 在美国，暴露在50%到100%之间的水供应 微克/L砷。研究地区的大多数其他供水设施包括 低于5微克/L，因此在暴露中提供了明显的对比。一个 2002年至2003年期间，研究区共确诊肺癌271例。 2004年将通过当地医院的快速病例确诊进行确认。 肿瘤活组织检查将被存档，以便进行潜在的DNA后续研究 改装。随机数字拨号与医疗融资的滚滚 将使用管理来为每个案例确定两个控制措施， 年龄和性别的频率匹配。对所有研究对象的电话采访 将收集有关终身居住历史和 将与水砷一起使用的饮用水水源 用于构建暴露历史的测量。这项研究的一个优点是 由于接触在很大程度上是 依赖于居住历史。关于吸烟的信息也将被 获得并评估了与砷的协同效应。饮食信息， 病史和人口统计数据将被收集和分析 潜在的易感因素。拟议中的研究有超过83%的 检测相对风险的统计能力为1.7，预测的风险 高剂量研究的线性外推。这项研究具有公共卫生意义 重要，因为找到假设的相对风险将识别 低水平暴露对健康的重要影响，而不是发现 风险增加将有助于确保公共卫生保护 从新的饮用水标准。

DESCRIPTION (provided by applicant): Millions of people are exposed to drinking water contaminated with arsenic, and extensive epidemiological evidence has demonstrated that these exposures can cause cancer. In fact, at high concentrations the levels of risk exceed those of any other known environmental carcinogen. At relatively low exposures such as those commonly found in the U.S., cancer risks from lifetime exposure could be above 1 in 1000 people, even at the newly proposed drinking water standard of 10 micrograms/L. In certain susceptible subpopulations, such as those who smoke or have poor diets, the risks may be even greater. Furthermore, our studies in Chile suggest particularly high risks for those drinking arsenic-contaminated water as children. Unfortunately, cancer risks at low exposures are uncertain since risk estimates to date involve extrapolation from high dose levels to lower exposures where the shape of the dose-response relationship is unknown. Such extrapolations are highly controversial. We therefore propose a population-based case-control study to assess the association of lung cancer with low to moderate levels of arsenic in drinking water. Current evidence indicates that lung cancer may be responsible for more deaths due to ingested arsenic than all other cancer sites combined, including bladder cancer. It is therefore particularly important to obtain a clear picture of the dose-response relationship for this cancer. The study area includes Kings County, California, and six counties in Nevada. These counties incorporate the largest population in the U.S. exposed to water supplies containing between 50 and 100 micrograms/L of arsenic. Most other water supplies in the study region contain less than 5 micrograms/L and thus provide a marked contrast in exposure. A total of 271 lung cancer cases diagnosed in the study area between 2002 and 2004 will be identified with rapid case ascertainment from local hospitals. Tumor biopsies will be archived for a potential subsequent study of DNA alterations. Random digit dialing and the rolls of the Health Care Financing Administration will be used to identify two controls for each case, frequency-matched by age and sex. Telephone interviews of all study subjects will be conducted to gather information on lifetime residential history and drinking water sources which will be used in conjunction with water arsenic measurements to construct exposure histories. A strength of the study is that exposure can be reliably ascertained retrospectively since it is largely dependent on residential history. Information on cigarette smoking will also be obtained and synergistic effects with arsenic assessed. Dietary information, medical history, and demographic data will be collected and analyzed for potential susceptibility factors. The proposed study has over 83 percent statistical power to detect a relative risk of 1.7, the risk predicted by linear extrapolation from high dose studies. The study has public health importance since finding the hypothesized relative risk would identify important health effects from low levels of exposure, whereas not finding increased risks would contribute to assurance about public health protection from the new drinking water standard.