ASSESSMENT OF URINARY MELATONIN IN EPIDEMIOLOGIC STUDIES

一些证据表明，褪黑激素可能抑制乳腺癌。然而，到目前为止，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。研究人员将从50名确诊为浸润性乳腺癌的女性和50名没有乳腺癌病史的女性中采集一份夜间/早晨空尿样本和4份白天斑尿样本。此外，在第一次收集后大约一个月，将从20名妇女（10名病例和10名对照）的子样本中获得第二组尿液样本，以评估个体内差异。病例将在治疗完成后登记。尿中褪黑素的主要代谢物- 6-硫代氧褪黑素（6-SMT）的水平将通过高度敏感和可靠的放射免疫分析法测定，肌酐将被测定。还将收集有关影响褪黑激素水平和乳腺癌风险因素的问卷调查数据。一些参数将被用来表征褪黑激素的排泄模式，包括夜间分泌高峰的女性比例、夜间平均水平和幅度（最大-最小6-SMT）。具体目的是：1)估计病例组和对照组中夜间峰值的比例、夜间平均水平和平均振幅，并确定这些参数在两组之间是否存在差异；2)通过重新采样女性子样本来评估6-SMT水平的个体内差异；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）；4)评估从日间尿样中预测夜间峰值水平。该项目将为设计调查褪黑素与乳腺癌和其他癌症关系的流行病学研究提供有价值的信息。如果很大一部分女性的尿频高峰出现在夜间，那么就有必要在白天收集额外的尿样。

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.