Circadian disruption and breast cancer from melatonin to clock genes
Circadian disruption and breast cancer from melatonin to clock genes
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DOI：
10.1097/01.ede.0000152525.21924.54
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发表时间：
2005-03-01
期刊：
影响因子：
5.4
通讯作者：
Stevens, RG
中科院分区：
文献类型：
--
作者：
Stevens, RG
乳腺癌对全球的影响是巨大的，而且还在不断增长。现代生活中的某些因素似乎是罪魁祸首，但迄今为止，对于社会工业化带来的风险增加，仍缺乏令人满意的解释。支持已经发展到一个可能的作用“昼夜节律中断”，特别是从一个改变照明的环境（如在夜间的光）。夜间足够强度的照明会扰乱昼夜节律，包括降低循环褪黑激素水平和重置视交叉上核的昼夜节律起搏器。褪黑激素减少可能通过几种机制增加乳腺癌风险，包括增加雌激素产生和改变雌激素受体功能。驱动昼夜节律的基因正在成为整个生物体基因调控的核心参与者，特别是细胞周期调控基因和细胞凋亡基因。现代生活的某些方面可能会在关键发育期（如子宫内和青春期）扰乱昼夜节律，这可能特别有害。流行病学研究应考虑基因和环境的相互作用，如昼夜基因变异和轮班工作的要求。
The global impact of breast cancer is large and growing. It seems clear that something about modem life is the culprit, yet there is thus far a lack of satisfactory explanations for most of the increases in risk as societies industrialize. Support has developed for a possible role of "circadian disruption," particularly from an altered-lighted environment (such as light at night). Lighting during the night of sufficient intensity can disrupt circadian rhythms, including reduction of circulating melatonin levels and resetting of the circadian pacemaker of the suprachiasmatic nuclei. Reduced melatonin may increase breast cancer risk through several mechanisms, including increased estrogen production and altered estrogen receptor function. The genes that drive the circadian rhythm are emerging as central players in gene regulation throughout the organism, particularly for cell-cycle regulatory genes and the genes of apoptosis. Aspects of modem life that can disrupt circadian rhythms during the key developmental periods (eg, in utero and during adolescence) may be particularly harmful. Epiderniologic studies should consider gene and environment interactions such as circadian gene variants and shift work requirements on the job.