Dietary and Environmental Exposure to Cadmium and the Risk of Endometrial Cancer

描述（由申请人提供）：暴露于无孕激素对抗的高水平循环雌激素是子宫内膜癌的主要原因。然而，对于模仿雌激素作用的环境污染物是否会增加患这种疾病的风险，人们知之甚少。镉是一种微量金属，作为工业过程的副产品释放到空气和土壤中，可能是这些雌激素污染物中最有效的子宫内膜癌病因。非职业性接触Cd的主要来源包括吸烟、饮食和吸入受工业过程和化石燃料燃烧污染的环境空气。这项拟议的研究将通过利用现有的饮食摄入、居住、吸烟史和其他危险因素的数据，以及356名被诊断患有子宫内膜癌的妇女和683名匹配的对照者的尿液样本，来验证更高水平的Cd暴露会增加子宫内膜癌风险的新假设，这些数据参加了教师营养、雌激素和子宫内膜癌（NEET）研究，这是加州教师研究（CTS）队列中的一项巢式病例对照研究。这些数据的可用性，用于测量Cd浓度的尿液样本（慢性暴露的经典测量方法），以及现有的环境和饮食Cd来源数据库，将使我们能够对包含无数来源的暴露进行全面评估，并评估每个来源的相对贡献。这也将使我们能够评估任何观察到的风险升高是否在不同暴露源之间存在异质性。本研究的具体目的将是：1)描述NEET研究中所有病例和对照者从饮食和环境来源暴露于镉的特征；2)评价饮食摄入和环境源暴露对尿中镉浓度的影响；3)评估饮食、环境和总镉暴露对子宫内膜癌风险的影响。新出现的证据表明，Cd是子宫内膜癌的潜在危险因素，这表明未来的方向是尽量减少饮食和环境对这种有毒金属的暴露。这项研究提供了一个独特而及时的机会，以提高我们对Cd是否在这种癌症的发展中起病因学作用的理解，并确定重要的，潜在的可改变的暴露于这种金属的来源。

DESCRIPTION (provided by applicant): Exposure to high levels of circulating estrogens unopposed by progestins is the primary cause of endometrial cancer. However, little is known about whether environmental contaminants that mimic the effects of estrogen increase the risk of this disease. Cadmium is a trace metal released into air and soil as a byproduct of industrial processes and is perhaps the most potent of these estrogenic contaminants with respect to endometrial cancer etiology. Major sources of non-occupational exposure to Cd include cigarette smoke, diet, and inhalation of ambient air contaminated by industrial processes and combustion of fossil fuels. This proposed study will test the emerging hypothesis that greater levels of Cd exposure increase endometrial cancer risk by utilizing existing data on dietary intake, residence, smoking history, and other risk factors and urine specimens from 356 women diagnosed with endometrial cancer and 683 matched controls enrolled in the Nutrition, Estrogens and Endometrial Cancer in Teachers (NEET) study, a nested case-control study within the California Teachers Study (CTS) cohort. The availability of these data, urine specimens for the measurement of Cd concentration-a classic measure of chronic exposure, and existing databases of environmental and dietary sources of Cd, will allow us to conduct a comprehensive assessment of exposure that incorporates a myriad of sources and evaluates the relative contribution of each source. This will also allow us to assess whether any observed elevations in risk are heterogeneous across exposure sources. The specific aims of this study will be to: 1) characterize exposure to Cd from dietary and environmental sources for all cases and controls in the NEET study; 2) evaluate the contributions of dietary intake and exposure from environmental sources on Cd concentrations measured in urine; and 3) estimate the effects of dietary, environmental, and total Cd exposure on the risk of endometrial cancer. The emerging evidence that Cd is a potential risk factor for endometrial cancer suggests a future direction for minimizing dietary and environmental exposures to this toxic metal. This study offers a unique and timely opportunity to improve our understanding of whether Cd plays an etiologic role in the development of this cancer and identify important, and potentially modifiable, sources of exposure to this metal. PUBLIC HEALTH RELEVANCE: Cadmium is a toxic metal known that is classified as a human carcinogen and is suspected of having estrogenic properties. By evaluating whether the risk of endometrial cancer is increased by exposure to cadmium, this proposed study offers a unique and timely opportunity to improve our understanding of a potentially modifiable risk factor for this disease and identify specific sources of cadmium that could be targeted for minimizing exposure.