Scott Davis (presenter) and Fred Hutchinson
Approximately one quarter of the workforce in North America and Europe engages in shift work requiring working at night. Those who work the night shift are exposed to artificial light-at-night, which suppresses the normal nocturnal production of melatonin, and can result in sleep disruption and deprivation. Night shift work has been associated with adverse health effects, including an increase in risk of breast cancer in women and prostate cancer in men.
A number of biological mechanisms have been proposed to explain these associations. This paper will summarize the evidence for direct action of melatonin as well as indirect action of circadian disruption on hypothesized pathways in cancer etiology.
Melatonin appears to influence the regulation of gonadal function by affecting the release of gonadotropins from the pituitary. Animal and human studies have shown that melatonin can stimulate testicular testosterone or ovarian estrogen production and release, thereby perhaps affecting hormone-dependent tumors. Melatonin may also have direct effects. Pharmacological concentrations of melatonin have been shown to have a direct antiproliferative and/or apoptotic effect on cancer cells in vitro, and physiological concentrations of melatonin have been shown to exert direct oncostatic effects on cancer cell proliferation. In addition to cell cycle effects, physiological melatonin concentrations are capable of reducing the activity of telomerase in MCF-7 cells in vitro, and melatonin is able to reduce the invasive and metastatic properties of MCF-7 cells. Melatonin also has a major role as an antiestrogen in estrogen-receptor-positive human breast cancer cell proliferation by suppressing the activity of the estrogen growth response pathway. Melatonin can reduce the formation of DNA adducts, can enhance immune response, and can act as a free radical scavenger.
These mechanisms will be considered in the context of providing a framework to evaluate the totality of the evidence regarding exposure to night work and the risk of specific cancers. The presentation will conclude with a discussion of key research priorities in this field.
Scott Davis, PhD, is Professor and Chairman of the Department of Epidemiology in the School of Public Health and Community Medicine at the University of Washington and a Full Member in the Program in Epidemiology of the Division of Public Health Sciences at the Fred Hutchinson Cancer Research Center. He obtained his undergraduate degree in Biology and Chemistry from the University of New Mexico, a Master of Science in Community Health from the University of Rochester, and a Ph.D. in Epidemiology from the University of Washington. He served as a Research Associate in Epidemiology at the Radiation Effects Research Foundation in Hiroshima, Japan, from 1983-1985. Dr. Davis was a Special Fellow of the Leukemia Society of American from 1986-1987, and the recipient of a Research Career Development Award from the National Cancer Institute from 1988-1993. He is an elected member of the American Epidemiological Society, and a Fellow of the American College of Epidemiology. He served as a member of the BEIR (Biological Effects of Ionizing Radiation) VII Committee of the National Academy of Sciences, and is an elected member (Academician) of the Russian Academy of Medical Sciences. He currently serves as a member of the National Cancer Institute Board of Scientific Counselors for Clinical Sciences and Epidemiology.
His primary research focus is radiation epidemiology. For more than a decade he has directed two major research activities investigating the effects of ionizing radiation on human health. One is a series of studies in the Russian Federation of the effects of radiation exposure from the Chernobyl Power Station. These studies have focused on the risk of thyroid cancer and leukemia among children in the Bryansk Oblast, and recently have expanded to include the molecular characterization of thyroid cancer cases and a large-scale study of breast cancer. The second is a long-term follow up study of thyroid disease in persons exposed to atmospheric releases of radiation from the Hanford Nuclear Site in eastern Washington State (the Hanford Thyroid Disease Study). He has also conducted several epidemiologic studies of the possible health effects associated with exposure to power frequency magnetic fields, focusing on the risk of leukemia and breast cancer. Recently this work has expanded to include investigations of the effects of exposure to light-at-night and circadian disruption, including night shift work, on melatonin and reproductive hormones important in the etiology of breast and other hormone-related cancer. He has also maintained a long-standing interest in the etiology of the leukemias and lymphomas, and has directed epidemiologic studies of Hodgkin’s disease, non-Hodgkin’s lymphoma, and multiple myeloma.