California Nevada Arsenic and Lung Cancer Study

描述（由申请人提供）：数百万人暴露于饮酒 被砷污染的水，以及广泛的流行病学证据， 表明这些暴露会导致癌症。事实上，在高 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曝光，如那些常见的在 美国，终生接触的癌症风险可能超过千分之一，甚至 新提出的饮用水标准为10微克/升。在某些 易感亚群，如吸烟或饮食不良的人， 风险可能更大。此外，我们在智利的研究表明， 特别是那些饮用砷污染水的人， 孩子不幸的是，低暴露的癌症风险是不确定的，因为风险 迄今为止的估计数是从高剂量水平外推到较低剂量水平 剂量-反应关系形状未知的暴露。等 外推是非常有争议的。因此，我们建议 以人群为基础的病例对照研究，以评估肺癌的相关性 饮用水中的砷含量为低到中等。目前的证据 表明肺癌可能是由于摄入 砷比所有其他癌症部位的总和，包括膀胱癌。是 因此，获得剂量反应的清晰图像尤为重要 这种癌症的关系。研究区域包括加州的金斯县， 还有内华达州的六个县这些县拥有最多的人口 在美国，暴露于含有50至100 微克/升砷。研究区域的大多数其他供水系统都含有 小于5微克/升，从而在曝光中提供显著的对比度。一 2002年至2009年，研究地区共诊断出271例肺癌病例， 2004年将通过当地医院的快速病例确定来确定。 肿瘤活检将存档，用于潜在的后续DNA研究 改变。随机数字拨号和卫生保健融资的名册 给药将用于为每种情况确定两种对照， 频率与年龄和性别相匹配。所有研究对象的电话访谈 将进行收集有关终身居住历史的信息， 饮用水源将与水砷结合使用 测量以构建暴露历史。这项研究的一个优点是， 暴露可以可靠地追溯确定，因为它在很大程度上是 取决于居住历史。此外，有关吸烟的资料亦会 获得并评估与砷的协同效应。饮食信息， 将收集和分析病史和人口统计学数据， 潜在易感因素。这项研究的结果显示， 检测相对风险的统计功效为1.7， 高剂量研究的线性外推。这项研究有公共卫生 重要性，因为找到假设的相对风险将确定 重要的健康影响，从低水平的接触，而不是发现 增加的风险将有助于确保公众健康保护 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.