RAPID METHOD FOR ANALYSIS OF ESTROGEN METABOLITES

除了主要的内源性雌激素外，特定的雌激素代谢物(包括16 α (OH)雌酮、4-（OH)雌酮和4-(OH)雌二醇）被认为对人类具有遗传毒性和潜在致癌性。尽管内源性雌激素代谢物在乳腺癌发生过程中具有潜在的重要性，但很少有研究调查其与人类乳腺癌风险的关系。雌激素代谢与乳腺癌的流行病学研究很少，仅报道了16 α (OH)雌酮和2-(OH)雌酮的排泄或两者之间的比例。这种数据缺乏的原因是雌激素代谢物分析的难度和费用。开发一种廉价、快速的方法将使大型流行病学研究能够确定特定雌激素代谢物与乳腺癌风险之间的关系，以及雌激素代谢物与肥胖和饮食等可改变的风险因素之间的关系。该项目的主要目的是开发一种快速、廉价的分析雌激素代谢物的方法，这将在大型流行病学研究中实际使用。此时，气相色谱-质谱“金标准”方法是非常劳动密集型的，而且在此类研究中使用过于昂贵。HPLC-MS/MS方法应该以更低的成本提供类似质量的数据。本项目的具体目的是建立一种HPLC-MS/MS分析尿液雌激素和雌激素代谢物的方法，并与“金标准”GC-MS方法进行验证。将对月经周期卵泡中期和黄体中期以及绝经后妇女的尿液进行两种方法的分析，以确定质量控制参数。这种方法的发展将使雌激素代谢和乳腺癌的大型流行病学研究的性能。

In addition to the major endogenous estrogens, specific estrogen metabolites (including 16alpha(OH) estrone, 4-(OH) estrone and 4-(OH) estradiol) are thought to be genotoxic and potentially carcinogenic in humans. Despite the potential importance of endogenous estrogen metabolites in breast carcinogenesis, few studies have investigated their association with human breast cancer risk. The few epidemiological studies of estrogen metabolism and breast cancer have reported only 16alpha(OH) estrone and 2-(OH) estrone excretion or the ration between the two. The reasons for this lack of data are the difficulty and expense of estrogen metabolite analysis. Development of an inexpensive, rapid method will enable the performance of large epidemiological studies to determine the associations between specific estrogen metabolites and breast cancer risk, as well as the associations between estrogen metabolites and modifiable risk factors such as obesity and diet. The main purpose of this project is to develop a rapid, inexpensive method of analysis of estrogen metabolites, that will be practical for use in large epidemiological studies. At this time, the GC-MS "gold standard" method is very labor intensive and much too expensive for use in such studies. An HPLC-MS/MS method should provide similar quality of data at a much lower cost. The specific aims of this project are to develop an HPLC-MS/MS method for analysis of urinary estrogens and estrogen metabolites, and to validate this method against the "gold standard" GC-MS method. Urine from the mid-follicular and mid-luteal phases of the menstrual cycle, a well as from post-menopausal women, will be analyzed for both methods for determination of quality control parameters. The development of this method will enable the performance of large epidemiological studies of estrogen metabolism and breast cancer.