Melatonin: Receptor-mediated events that may affect breast and other steroid hormone–dependent cancers

Abstract

Epidemiological studies have suggested a possible link between extremely low frequency electromagnetic fields (EMFs) and increased rates of certain cancers. One cancer that has been postulated to be associated with EMF exposure is breast cancer, for which increased rates have been reported among electricians. These cancer associations are weak, and the link to EMF exposures remains tenuous. Understanding the mechanisms by which EMFs could have biological effects will help in elucidating the risk, if any, from EMFs. One hypothesis that has received considerable attention involves reduction of melatonin levels by EMFs. This hypothesis suggests that loss of melatonin affects a variety of hormonal processes such as estrogen homeostasis and thereby may increase breast cancer rates. Since this theory was first presented, putative melatonin receptors have been cloned, providing new tools with which to examine melatonin's mechanism of action and the melatonin hypothesis. These receptors are found in nuclear and membrane fractions of cells. The nuclear receptors (retinoid Z receptors) are found both in the brain and in non-neural tissues, whereas the membrane-bound receptors are found primarily in neural tissue and have a higher affinity for melatonin. These receptors may control a variety of hormonal and immunological functions, including the release of gonadotropins from the hypothalamus and pituitary and 5-lipoxygenase activity in B lymphocytes. This Working Hypothesis briefly reviews our current knowledge of melatonin receptors and then provides theories on how the inactivation of melatonin receptors may cause cancer and suggests areas of research for addressing this question.

Residential magnetic fields as a risk factor for childhood acute leukaemia: Results from a German population-based case-control study

“…It has been hypothesized that exposure to higher magnetic fields suppresses the nocturnal production and release of the hormone melatonin, which is assumed to have oncostatic capabilities; 31,32 however, the melatonin hypothesis has been proposed for breast cancer and hormone-dependent cancers rather than leukaemia. 33,34 Nevertheless, young children have higher melatonin levels than adults; 35 therefore, effects caused by reduced melatonin concentrations might be more marked. So far, there is weak supportive evidence for the melatonin hypothesis from human laboratory studies.…”

Inverse association between breast cancer incidence and degree of visual impairment in Finland

“…Presuming that melatonin has a real anticarcinogenic property, the breast-cancer-specific decrease may point to a mechanism with an intermediary role for oestrogens (Blask et al, 1991;Baldwin and Barret, 1998) in the biophysical/chemical pathway from visible light to endogenous melatonin secretion and, finally, to the development of breast cancer. It is pertinent, however, that it is not known.…”

Cryptochrome: The Second Photoactive Pigment in the Eye and Its Role in Circadian Photoreception

“…This so-called melatonin hypothesis proposes that the suppression of melatonin secretion at night by artificial light increases breast cancer risk by increasing exposure to estrogen (168,169). Since the isolation of melatonin receptors and the finding of widespread expression of these receptors in neural and nonneural tissues (170,171), the scope of the melatonin hypothesis has expanded to include other mechanisms by which reduced melatonin concentrations may affect hormone homeostasis and induce breast and perhaps other cancers (172). A retrospective survey found that severely blind women had about half the incidence of breast cancer of women with normal vision (173).…”