Circadian mechanisms in the regulation of melatonin synthesis: disruption with light at night and the pathophysiological consequences

Abstract

In the past two decades, the results of a number of epidemiological studies have uncovered an association between excessive light exposure at night and the prevalence of cancer. Whereas the evidence supporting this link is strongest between nighttime light and female breast and male prostate cancer, the frequency of other tumor types may also be elevated. Individuals who have the highest reported increase in cancer are chronic night shift workers and flight attendants who routinely fly across numerous time zones. There are at least two obvious physiological consequences of nighttime light exposure, i.e., a reduction in circulating melatonin levels and disruption of the circadian system (chronodisruption). Both these perturbations in experimental animals aggravate tumor growth. Melatonin has a long investigative history in terms of its ability to stymie the growth of many tumor types. Likewise, in the last decade chronodisruption has been unequivocally linked to a variety of abnormal metabolic conditions including excessive tumor growth. This brief review summarizes the processes by which light after darkness onset impedes melatonin production and disturbs circadian rhythms. The survey also reviews the evidence associating the ostensible danger of excessive nighttime light pollution to cancer risk. If an elevated tumor frequency is definitively proven to be a consequence of light at night and/or chronodisruption, it seems likely that cancer will not be the exclusive pathophysiological change associated with the rampant light pollution characteristic of modern societies.