Deregulation of the circadian clock constitutes a significant factor in tumorigenesis: a clockwork cancer. Part I: clocks and clocking machinery

Abstract

Many physiological processes occur in a rhythmic fashion, consistent with a 24-h cycle. The central timing of the day/night rhythm is set by a master clock, located in the suprachiasmatic nucleus (a tiny region in the hypothalamus), but peripheral clocks exist in different tissues, adjustable by cues other than light (temperature, food, hormone stimulation, etc.), functioning autonomously to the master clock. Presence of unrepaired DNA damage may adjust the circadian clock so that the phase in which checking for damage and DNA repair normally occurs is advanced or extended. The expression of many of the genes coding for proteins functioning in DNA damage-associated response pathways and DNA repair is directly or indirectly regulated by the core clock proteins. Setting up the normal rhythm of the circadian cycle also involves oscillating changes in the chromatin structure, allowing differential activation of various chromatin domains within the 24-h cycle.

Chronodisruption and Ambulatory Circadian Monitoring in Cancer Patients: Beyond the Body Clock

“…Although sleep impairment and fatigue experienced by cancer patients are generally believed to be iatrogenic, partly caused by the psychological impact and the physiological consequences of anti-cancer treatments, further evidence is needed to determine its possible effect on tumorigenesis activation [ 109 , 110 ]. In 2016, Erren and colleagues performed a meta-analysis of sleep and cancer incidence among more than 1,500,000 subjects from 13 countries and, although they failed to find a clear answer to the question of how cancer and sleep are connected in humans, authors concluded that a complex chronobiological relationship, presumably multidirectional, is plausible [ 111 ].…”

Are sleep continuity disturbance and fatigue prodromal symptoms of cancer development?

“…11 Collectively, these findings suggest that sleep continuity disturbance may not only be a consequence of the cancer diagnosis and treatment but may also represent a risk factor for the development of the disease or be the activating trigger for tumorigenesis. 12,13…”