Light at Night and Melatonin
USED IN: Night shift workers
Several epidemiological studies have demonstrated that women who consistently work night shifts have increased breast cancer risk. Two major reviews of the literature, one examining only studies of night shift nurses (Kolstad, 2008) and a second looking at studies of airline crews and other night shift workers (Megdal, 2005), reached the conclusion that long-term experience in night shift work increases risk for breast cancer about 1.5- to 2.5-fold (Stevens, 2009). These results are of concern, as about 15 percent of the U.S. work force currently works at least some of the time on non-day shifts, and the proportion of workers engaged in night shift work disproportionately falls to African Americans (Costa, 2010).
The most studied mechanism to explain these effects of night shift work is called the Light-at-Night (LAN) hypothesis (Stevens, 2009). Increasing exposure to light, especially bright indoor lights, at times outside of normal daylight hours, decreases secretion of melatonin (Stevens, 2009). Melatonin is a hormone secreted by the pineal gland in response to decreases in ambient light. Normal high levels of melatonin at nighttime are important for regulation of both pituitary and ovarian hormones (including estradiol), and also for increasing the efficiency of cell proliferation and DNA-repair mechanisms, enhancing the activity of pathways that can prevent the development of cancer (Blask, 2009; Cos, 2000).
Clinical studies have demonstrated that there is a decrease in the peak amount of melatonin secreted in women with metastatic cancer, as compared with healthy women, and larger tumors are associated with lower levels of melatonin (Cos, 2000).
A recent study examined satellite images of 147 communities and compared the co-distribution of LAN and cancer incidence across these communities. A significant positive relationship was found between intensity of night light and breast cancer, but no such relationship was found between night light intensity and lung cancer (Kloog, 2008).
In further support of the LAN hypothesis, blind women who are completely unable to perceive the presence of environmental light, and therefore have no daily decreases in melatonin levels, have significantly lower risk of diagnosis of breast cancer than do blind women who do perceive light and have regular decreases in melatonin secretion over the normal 24-hour cycle. This effect, along with its opposite in the night shift work model, both support the conclusion that the greater the secretion of melatonin, the lower the risk of breast cancer (Flynn-Evans, 2009).
In rodent models, higher levels of melatonin are associated with decreased incidence and size of mammary tumors, and when they do occur, the latency period of tumor development is lengthened (Cos, 2000).
One study examined the effects of blood (containing naturally secreted melatonin) taken from women during the day; women during the night (also with natural melatonin); women during the night who had been given a drug that blocked the secretion of melatonin; and women during the night who were exposed to bright white lights. The blood was injected into human mammary tumors that had been xenografted into laboratory mice. Blood from natural nighttime samples significantly decreased proliferation and growth of mammary tumors, as compared to samples collected during the day. If the blood samples came from women who had either been treated with a melatonin blocker or exposed to bright white lights, this protective effect of nighttime sampling was eliminated (Blask, 2005). In these studies, greater intensity of white light led to lower melatonin secretion rates and greater tumor growth rates (Blask, 2009).
Several recent studies have indicated that genes that are associated with the regulation of the daily melatonin cycle also regulate other pathways that may be involved in the development of breast cancer. For example, structural variation in the gene Per3 is associated with higher breast cancer rates in young women (Zhu, 2008). Per2, another gene associated with the control of daily rhythms, is also poorly regulated in many women with breast cancer, with normal structure and expression of this gene being associated with lower effectiveness of estradiol in altering cellular activity. In healthy cells, Per2 also may act directly as a tumor-suppressor gene, decreasing the activity of pathways associated with tumor formation (Gery, 2007).
