Circulating melatonin and the risk of breast and endometrial cancer in women

Abstract

Several decades of observational data have accumulated to implicate a potential role for melatonin in cancer prevention. Experimental studies suggest that the antineoplastic action of melatonin arises through many different mechanisms, including melatonin's antioxidant, antimitotic, and antiangiogenic activity, as well as its ability to modulate the immune system and alter fat metabolism. Melatonin interacts with membrane and nuclear receptors, and may be linked to the regulation of tumor growth. Of particular relevance to breast cancer risk, melatonin may also block the estrogen receptor ERα and impact the enzyme aromatase, which produces estradiol. A growing number of epidemiologic studies have evaluated the relationship between night shift work as well as how varying duration of sleep affects peak melatonin secretion at night. While the studies demonstrate lower nightly melatonin levels in night workers, the evidence for an association between sleep duration and melatonin production is less clear. Similarly, both case-control and prospective cohort studies have consistently linked night shift work with breast cancer risk and, more recently, endometrial cancer-another tumor highly sensitive to estrogens. While, to date, the evidence for an association between sleep duration and breast cancer risk is less convincing, overall, there is increasing support for a potentially important link between melatonin and breast cancer risk and perhaps the risk of other tumors. As evidence increases, modifiable factors that have been shown to affect melatonin production, such as night shift work, are likely to gain increasing recognition as potential public health hazards. Additional studies are needed to delineate further the potential of melatonin in cancer prevention.

Night work and breast cancer – results from the German GENICA study

“…Artificial light at night can modify the diurnal melatonin production. It has been proposed that suppressed melatonin production may lead to an increased cancer risk, but further research is needed to fully establish the mechanistic pathways leading to circadian disruption and cancer (24)(25)(26)(27)(28). However, cancer as a systemic disease or the treatment thereof can interfere with biomarker levels, making case-control studies less suitable for the determination of melatonin and other biomarkers.…”

Emerging functional roles of nuclear receptors in breast cancer

“…Many studies suggest that lowered melatonin level due to exposure to night light contributes toward breast cancer development and drug resistance. Melatonin is thought to exert its oncostatic effect through multiple mechanisms including antimitosis, anti-angiogenesis, anti-oxidation and regulation of immune response (Viswanathan & Schernhammer 2009). The oncostatic effect of melatonin in breast cancer is thought be mediated through its anti-estrogenic actions as well as its role in regulating the activity of aromatases, the enzymes responsible for the local biosynthesis of estrogens from androgens (Cos et al 2006).…”

Hormones, hormonal agents, and neuropeptides involved in the neuroendocrine regulation of sleep in humans

“…96 On the other hand, both case-control and prospective cohort studies have consistently linked night shift work with breast cancer risk and, more recently, endometrial cancer, both of which are highly sensitive to estrogens. 97 Despite the proven effects of estrogens on sleep regulation, women starting HRT often also take progesterone to protect themselves against the harmful endometrial effects of estrogens. Studies of progesterone's effects on sleep have yielded variable results.…”

“…Although the evidence for an association between sleep duration and breast cancer risk is unclear, overall there is increasing support for a potentially important link between melatonin and breast cancer risk. 97 A possible link between diminished secretion of melatonin and increased exposure to light during night-time has been suggested. 116 Ultimately, genome-wide association studies [117][118][119] have shown that variation in the melatonin receptor 1B (MTNR1B)-a receptor known to be linked to the circadian rhythm of sleep-is associated with insulin and glucose concentrations as well as with the risk of type 2 diabetes (T2D).…”