David E. Blask (presenter) and Robert T. Dauchy
This presentation summarizes the state of research evidence on the impact of circadian disruption on cancer risk in animals. We explore the extent to which this evidence sheds light on the cancer risk faced by shift workers.
The regular alteration in the light/dark cycle over each 24 hour period is the major synchronizer of the endogenous circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the brain in all mammals including humans. The SCN is active during the day stimulating a variety of hormonal, metabolic and behavioral responses so that internal physiology is in sync with the external environment. The inactivity of the SCN at night allows pineal gland production of melatonin, a potent anti-cancer hormone. High nocturnal blood levels of melatonin are responsible for telling all the cells of the body, including cancer cells, that it is nighttime. Changes in either the length of the day or its timing/phasing can compromise SCN activity and the pineal gland production of melatonin, a phenomenon referred to as circadian disruption. Another aspect of circadian disruption relates to the suppression of the nocturnal circadian melatonin signal resulting from the exposure of an organism to light during the night.
The central biological timing mechanism provided by the SCN, including nocturnal melatonin production, has a profound impact on the development and growth of a variety of experimental malignancies in animal models of cancer. Circadian disruption caused by either increasing the duration of daily light exposure, chronically advancing the phasing of light exposure (chronic jet lag) or light at night-induced suppression of the nocturnal circadian melatonin signal stimulates the development and growth of experimental tumors. Evidence appears to be sufficiently strong for circadian disruption-induced promotion of cancer development and growth in animal models of cancer. However, it is not currently known the extent to which alterations in the light/dark environment in the experimental setting mimic what is actually experienced by shift workers. As such, their relevance to increased cancer risk in this population remains a limitation that requires new experimental approaches. The presentation will conclude with a summary of the limitations of research published to date and will propose key research priorities for the future.
David E. Blask, Ph.D., M.D. is Professor and Head, Laboratory of Chrono-Neuroendocrine Oncology, Department of Structural and Cellular Biology, Tulane University School of Medicine, Tulane Cancer Center and Louisiana Cancer Research Consortium, New Orleans, Louisiana.
For over 30 years, Dr. Blask’s research has focused on the circadian control and therapeutics of cancer by melatonin as well as the consequences of the circadian disruption of melatonin production by light at night on cancer risk. He has published over 250 journal articles, reviews, chapters and abstracts on this topic. His research has been supported by funding agencies such as the National Cancer Institute, National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences and The Edwin Pauley Foundation. He currently serves on the editorial boards of the Journal of Pineal Research, Neuroendocrinology Letters and Integrative Cancer Therapies and is a consultant for the photobiology group of the International DarkSky Association. Dr. Blask has also served as a member of the working group on shift work for the International Agency for Cancer Research of the World Health Organization.