ASSESSMENT OF URINARY MELATONIN IN EPIDEMIOLOGIC STUDIES

几条证据表明褪黑激素可能抑制乳腺癌。然而，到目前为止，还没有乳腺癌的流行病学研究包括褪黑激素水平的评估。本研究的总体目标是确定如何可靠地测量褪黑激素水平用于流行病学研究。将从50名诊断为浸润性乳腺癌的女性和50名无乳腺癌既往史的女性中采集一份夜间/早晨尿液样本和全天4份日间尿液样本。此外，将在首次采集后约1个月从20名女性（10例病例和10例对照）的子样本中获得第二组尿样，以评估个体内变异。病例将在治疗完成后入组。将通过高度灵敏和可靠的放射免疫测定法测定尿中褪黑激素的主要代谢物6-硫酸氧褪黑激素（6-SMT）的水平，并测定肌酐。还将收集关于影响褪黑激素水平的因素和乳腺癌风险因素的问卷数据。 将使用许多参数来表征褪黑激素排泄模式，包括在夜间达到峰值的女性比例、平均夜间水平和振幅（最大值-最小值6-SMT）。具体目标是：1）估计病例组和对照组之间具有夜间峰值、平均夜间水平和平均振幅的比例，并确定这些参数在两组之间是否存在差异; 2）通过对女性子样本进行重新抽样，评估6-SMT水平的个体内变异; 3）确定6-SMT参数的预测因子（包括睡眠时间、酒精摄入量、体重指数和其他变量）;和4）评估来自日间现场尿样的峰值夜间水平的预测。该项目将为调查褪黑激素与乳腺癌和其他癌症关系的流行病学研究设计提供有价值的信息。如果很大一部分女性的高峰期在夜间以外，这就说明有必要在一天中收集额外的尿液样本。

Several lines of evidence suggest that the hormone melatonin may inhibit breast cancer. However, to date no epidemiologic studies of breast cancer have included assessment of melatonin levels. The overall objective of this study is to determine how to reliably measure melatonin levels for use in epidemiologic studies. A nocturnal/ morning void urine sample and 4 daytime spot urine samples throughout the day will be obtained from 50 women diagnosed with invasive breast cancer and 50 women with no prior history of breast cancer. In addition, a second set of urine samples will be obtained from a subsample of 20 women (10 cases and 10 controls) approximately one month after the first collection in order to assess intra- individual variation. Cases will be enrolled after completion of treatment. Levels of 6-sulfatoxymelatonin (6-SMT), the major metabolite of melatonin in urine, will be determined by a highly sensitive and reliable radio-immunoassay, and creatinine will be assayed. Questionnaire data will also be collected on factors thought to influence melatonin levels and on breast cancer risk factors. A number of parameters will be used to characterize melatonin excretion patterns, including the proportion of women with a peak during the nocturnal hours, mean nocturnal level, and the amplitude (maximum - minimum 6-SMT). The specific aims are: l) to estimate the proportion with a nocturnal peak, the mean nocturnal level, and the mean amplitude among cases and controls and to determine whether these parameters differ between the two groups; 2) to assess intra-individual variation in 6-SMT levels by resampling a subsample of women; 3) to identify predictors of 6-SMT parameters (including sleep hours, alcohol intake, body mass index, and other variables); and 4) to assess the prediction of peak nocturnal levels from a daytime spot urine sample. This project will provide valuable information for the design of epidemiologic studies investigating the relationship of melatonin to breast and other cancers. If a significant proportion of women have their peak outside the nocturnal period, this would argue for the necessity of collecting additional urine samples throughout the day.