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

描述(由申请人提供)：暴露于高水平的循环雌激素而不被孕激素对抗是子宫内膜癌的主要原因。然而，人们对模仿雌激素效应的环境污染物是否会增加这种疾病的风险知之甚少。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与子宫内膜癌病因相关的最有效的。非职业性接触镉的主要来源包括香烟烟雾、饮食和吸入受工业过程和化石燃料燃烧污染的环境空气。这项拟议的研究将利用现有的饮食摄入量、居住地、吸烟史和其他危险因素的数据，以及参加加州教师研究(CTS)队列中嵌套的病例对照研究(NEET)的356名被诊断为子宫内膜癌的女性和683名匹配的对照组的尿样，来检验新出现的假设，即更高水平的镉暴露会增加子宫内膜癌的风险。这些数据的可获得性、用于测量镉浓度的尿样--这是一种衡量慢性接触的经典指标--以及现有的镉的环境和饮食来源数据库，将使我们能够对接触情况进行全面评估，包括各种来源，并评估每个来源的相对贡献。这也将使我们能够评估是否任何观察到的风险升高在不同的暴露来源之间是不同的。这项研究的具体目标是：1)确定NEET研究中所有病例和对照组从饮食和环境来源摄入Cd的特征；2)评估饮食摄入和环境来源暴露对尿镉浓度的贡献；以及3)估计饮食、环境和总Cd暴露对子宫内膜癌风险的影响。新出现的证据表明，镉是子宫内膜癌的潜在危险因素，这表明了未来将这种有毒金属的饮食和环境暴露降至最低的方向。这项研究提供了一个独特和及时的机会，以提高我们对镉是否在这种癌症的发展中起病因学作用的理解，并确定接触这种金属的重要的和潜在的可改变的来源。 与公众健康相关：镉是一种已知的有毒金属，被归类为人类致癌物质，并被怀疑具有雌激素性质。通过评估镉暴露是否会增加子宫内膜癌的风险，这项拟议的研究提供了一个独特和及时的机会，以提高我们对这种疾病的潜在可改变风险因素的理解，并确定可以针对最大限度减少接触的特定镉来源。

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.