University of Connecticut Health Center, Farmington, CT 06032, United States.
Mutat Res. 2009 Nov-Dec;680(1-2):106-8. doi: 10.1016/j.mrgentox.2009.08.004.
Breast cancer incidence increases rapidly as societies industrialize. Many changes occur during the industrialization process, one of which is a dramatic alteration in the lighted environment from a sun-based system to an electricity-based system. Increasingly, the natural dark period at night is being seriously eroded for the bulk of humanity. Based on the fact that light during the night can suppress melatonin, and also disrupt the circadian rhythm, it was proposed in 1987 that increasing use of electricity to light the night accounts in part for the rising risk of breast cancer globally. Predictions from the theory include: non-day shift work increases risk, blindness lowers risk, long sleep duration lowers risk, and population level community nighttime light level co-distributes with breast cancer incidence. Thus far, studies of these predictions are consistent in support of the theory. A new avenue of research has been on function of circadian genes and whether these are related to breast cancer risk. In particular, a length variant of Per3 (5-VNTR) has been associated with increased risk in young women, and this same 5-VNTR variant has also been found to predict morning diurnal type and shorter sleep duration compared to the 4-VNTR variant. An important question is how an effect of light-at-night (LAN) exposure on breast cancer risk might be modified by polymorphisms and/or epigenetic alterations in the circadian genes, and conversely whether light-at-night exposure (e.g., shift work) can induce deleterious epigenetic changes in these genes.
乳腺癌发病率随着社会工业化而迅速上升。在工业化进程中会发生许多变化，其中之一是照明环境从基于太阳的系统到基于电力的系统的剧烈改变。越来越多的自然夜间黑暗期正在被严重侵蚀，这对大多数人类来说都是如此。基于夜间的光线可以抑制褪黑素，并且还会破坏昼夜节律这一事实，有人在 1987 年提出，夜间使用越来越多的电力照明部分解释了全球乳腺癌风险的上升。该理论的预测包括：非轮班工作会增加风险，失明会降低风险，睡眠时间长会降低风险，以及人群夜间社区光照水平与乳腺癌发病率共同分布。到目前为止，这些预测的研究结果一致支持该理论。一个新的研究领域是关于昼夜节律基因的功能，以及这些基因是否与乳腺癌风险有关。特别是，Per3（5-VNTR）的长度变体与年轻女性的风险增加有关，与 4-VNTR 变体相比，相同的 5-VNTR 变体还发现与早晨的日间类型和较短的睡眠时间有关。一个重要的问题是，夜间光照（LAN）暴露对乳腺癌风险的影响如何可能会被昼夜节律基因中的多态性和/或表观遗传改变所修饰，反之亦然，夜间光照暴露（例如轮班工作）是否会导致这些基因的有害表观遗传改变。
