DESCRIPTION (provided by applicant): The primary objective of the proposed study is to determine whether working at night is associated with the following in a sample of healthy men: decreased urinary concentration of 6-sulphatoxymelatonin; increased serum concentrations of testosterone, dihydrotesterone (DHT), 3-a androstanediol glucuronide, dehydroepiandrosterone (DHEA) sulfate, estrone, and estradiol; increased urinary concentrations of the following androgen metabolites: conjugated testosterone, DHT, etiocholanolone, androsterone, androstanediol, and DHEA; and decreased serum concentration of sex hormone-binding globulin. The study will also investigate: 1) whether urinary levels of melatonin are lower and serum and urinary levels of the androgens and metabolites listed above are higher during daytime sleep relative to nighttime sleep among men who work at night; and 2) if specific polymorphisms of the human circadian clock genes are associated with an individual's ability to adapt to night shift work. Approximately 200 male health care workers who work the night shift and 150 who work the day shift will be recruited in the Seattle metropolitan area. Eligible participants must be 22-55 years old, employed for at least 20 hours/week, not taking hormone preparations, and have no history of prostate cancer. This study will allow for both between-subject comparisons of night shift v. day shift workers, and within-subject comparisons during day sleep v. night sleep among night shift workers. Participation includes an in-person interview, assessment of ability to adapt to shiftwork, and blood and urine collections during both work and sleep periods. Sleep quality and quantity will be measured via actigraphy during the sleep periods corresponding to sample collection. Information will be collected on factors that may be related to the hormones under study, such as alcohol consumption, medication use, and hours of daylight during sample collection. Serum and urine samples will be assayed for the hormones and metabolites listed above, and blood samples will be genotyped for specific polymorphisms of the human CLOCK, PER2, and PER3 genes. This study will be the first effort to assess the effects of night shift work on melatonin and the hormones of most interest in the etiology of prostate cancer. Results will provide important new information regarding the underlying biological basis of the emerging evidence linking night shift work with cancer risk.
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