The effect of melatonin on the prevention of breast cancer has now been demonstrated as reported in the December 2001 Issue of the Neuroendocrinology Letters - an International Medical Journal.
The experiment showed that exposure to constant light promoted mammary carcinomas development whereas rhythmical treatment with melatonin substantially prevents it.
As previously reported, according to the International Agency for Research on Cancer Report (D.M.Parkin et al.), breast cancer constituted a huge disease burden in developed countries in the year 2000 as reflected in the Global Cancer Burden Picture (Eur.J.Cancer, 2001, 37, S4-S66). It is the most common cancer in women with an estimated 999,000 new cases of breast cancer each year (about 22% of cancers in women) resulting in some 375,000 deaths.
More than half of all cases are registered in industrialized countries: about 335,000 in Europe and 195,000 in North America. The disease is not yet as common among women in developing countries although proliferation is increasing. Risk of breast cancer incidence had been associated with higher socio-economic status such as income, education, housing, etc. as they were related to such health factors as age at menstruation and menopause, obesity, height, alcohol consumption, late age at first birth, low parity, estrogen replacement therapy, some diet habits, etc. Two conditions unique to developed countries are an increasing exposure to light-at-night and power frequency (50-60 Hz) magnetic fields.
The light-at-night is a life style factor now shown to be significant. The alternation of the day and night circadian cycle is a most important regulator of a wide variety of physiological rhythms in living organisms. Light exposure at night has been found to be related to a number of serious behavioral as well as health problems including cancer. Fruit fly experiments have shown that exposure to constant light (24 hours a day) was followed by a shortening of their life spans. In rodents, light-at-night leads to disruption of the ovulatory cycle followed by hyperplastic processes in mammary gland, ovarian and uterine tumor development. This was shown in the tumor-promoting effect of light exposure on mammary gland carcinogenesis (cancer) in mice and rats. Prolonged light exposure suppresses the night peak release of melatonin - the 'hormone of the night'. Melatonin is a principal hormone of the pineal gland - the small neuroendocrine gland connected with the brain which mediates information on light from the retina of the eyes to the organism.
On October 17, the Journal of the National Cancer Institute (2001, Vol. 93, No. 20, pp. 1557-1562 and 1563-1568 published two papers reporting a significant increase in the risk of breast cancer among women who frequently did not sleep during the period of the night, about 1:30 a.m., when melatonin levels are typically at their highest. There was increased risk among women sleeping in the brightest bedrooms. Moreover, women who had worked 30 and more years on rotating night shifts had a 36% greater risk of breast cancer compared with workers who had never worked nights. Earlier, epidemiologists had shown an elevated breast cancer risk among post-menopausal radio and telegraph operators exposed to shift work as well as among flight attendants working markedly random night periods. 'Melatonin hypothesis' suggests that reduced pineal melatonin production might increase human breast cancer risk because lower melatonin output would lead to an increase in the level of female sex hormones and would stimulate proliferation of breast tissue. However, the exact mechanisms of the connection of melatonin inadequacy with breast cancer had not been well explored.
Now, a joint team of researchers from N.N. Petrov Research Institute of Oncology (St. Petersburg) and the Italian National Research Center of Aging (Ancona) exposed harboring gene HER-2/neu female mice to either constant light or standard (12 hours light/12 hours darkness) regimens and nightly treated mice from both groups with melatonin dissolved in drinking water (D.A. Baturin et al., Neuroendocrinology Letters, 2001, 22, December, 439-445). It is worthy of note that this gene plays a pathogenetic role in several malignancies, including carcinoma of the breast, ovary and uterus, in humans. Over-expression of the HER-2/neu gene occurs in 15-40% of human breast cancers and is associated with poor prognosis. In the experiment, it was shown that exposure to constant light promoted mammary carcinomas development whereas rhythmical treatment with melatonin substantially prevents it. Moreover, melatonin treatment resulted in a 2.5 fold reduction in the expression of the HER-2/neu oncogene in mammary tumors of transgenic mice. Thus, for the first time, a new mechanism has been found by which melatonin may bring about its anti-cancer action preventing the development of breast cancer. Whether melatonin may directly act on tumor cells inhibiting the gene expression or its effect is indirectly due to the modulation of other factors in the organism remains to be demonstrated. At present, the teams are working in this direction. (V.N. Anisimov)