Davis Scott, Mirick Dana K
Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, and Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98109-1024, USA.
Cancer Causes Control. 2006 May;17(4):539-45. doi: 10.1007/s10552-005-9010-9.
There is increasing interest in the possibility that disruption of normal circadian rhythm may increase the risk of developing cancer. Persons who engage in nightshift work may exhibit altered nighttime melatonin levels and reproductive hormone profiles that could increase the risk of hormone-related diseases, including breast cancer. Epidemiologic studies are now beginning to emerge suggesting that women who work at night, and who experience sleep deprivation, circadian disruption, and exposure to light-at-night are at an increased risk of breast cancer, and possibly colorectal cancer as well. Several studies have been conducted in Seattle recently to investigate the effects of factors that can disrupt circadian rhythm and alter normal nocturnal production of melatonin and reproductive hormones of relevance to breast cancer etiology. Studies completed to date have found: (1) an increased risk of breast cancer associated with indicators of exposure to light-at-night and night shift work; and (2) decreased nocturnal urinary levels of 6-sulphatoxymelatonin associated with exposure to 60-Hz magnetic fields in the bedroom the same night, and a number of other factors including hours of daylight, season, alcohol consumption and body mass index. Recently completed is an experimental crossover study designed to investigate whether exposure to a 60-Hz magnetic field under controlled conditions in the home sleeping environment is associated with a decrease in nocturnal urinary concentration of 6-sulphatoxymelatonin, and an increase in the urinary concentration of luteinizing hormone, follicle stimulating hormone, and estradiol in a sample of healthy women of reproductive age. Presently underway is a study to determine whether working at night is associated with decreased levels of urinary 6-sulphatoxymelatonin, and increased urinary concentrations of the reproductive hormones listed above in a sample of healthy women of reproductive age, and to elucidate characteristics of sleep among night shift workers that are related to the hormone patterns identified. A proposal is under review to extend these studies to a sample of healthy men to investigate whether working at night is associated with decreased levels of urinary 6-sulphatoxymelatonin, and increased concentrations of urinary cortisol and cortisone, urinary levels of a number of androgen metabolites, and serum concentrations of a number of reproductive hormones. Secondarily, the proposed study will elucidate characteristics of sleep among night shift workers that are related to the hormone patterns identified, as well as investigate whether polymorphisms of the genes thought to regulate the human circadian clock are associated with the ability to adapt to night shift work. It is anticipated that collectively these studies will enhance our understanding of the role of circadian disruption in the etiology of cancer.
正常昼夜节律的紊乱可能会增加患癌风险，这一可能性正引发越来越多的关注。从事夜班工作的人可能会出现夜间褪黑素水平和生殖激素谱的改变，这可能会增加患激素相关疾病的风险，包括乳腺癌。流行病学研究现在开始出现，表明夜间工作且经历睡眠剥夺、昼夜节律紊乱和夜间暴露于光线下的女性患乳腺癌的风险增加，可能患结直肠癌的风险也会增加。最近在西雅图进行了几项研究，以调查可能扰乱昼夜节律并改变与乳腺癌病因相关的褪黑素和生殖激素正常夜间分泌的因素的影响。迄今为止完成的研究发现：（1）与夜间暴露于光线下和夜班工作的指标相关的乳腺癌风险增加；（2）与同一晚卧室中暴露于60赫兹磁场相关的夜间尿中6-硫酸氧褪黑素水平降低，以及包括日照时间、季节、酒精摄入量和体重指数在内的许多其他因素。最近完成的一项实验性交叉研究旨在调查在家庭睡眠环境的受控条件下暴露于60赫兹磁场是否与育龄健康女性样本中夜间尿中6-硫酸氧褪黑素浓度降低以及促黄体生成素、促卵泡激素和雌二醇尿浓度增加有关。目前正在进行一项研究，以确定夜间工作是否与育龄健康女性样本中尿中6-硫酸氧褪黑素水平降低以及上述生殖激素尿浓度增加有关，并阐明夜班工作者与所确定的激素模式相关的睡眠特征。一项将这些研究扩展到健康男性样本的提案正在审核中，以调查夜间工作是否与尿中6-硫酸氧褪黑素水平降低以及尿皮质醇和可的松浓度增加、多种雄激素代谢物的尿水平以及多种生殖激素的血清浓度增加有关。其次，拟议的研究将阐明夜班工作者与所确定的激素模式相关的睡眠特征，以及调查被认为调节人体昼夜节律的基因多态性是否与适应夜班工作的能力有关。预计这些研究将共同增进我们对昼夜节律紊乱在癌症病因学中作用的理解。
