Table 1.

Summary of the connections between circadian rhythms and cancer.

Cell Cycle Progression
	Transitions from cell cycle phases are controlled by time windows established by the biological clock.	[26,27]
CDK/cyclin B1	Circadian controlled by Wee1, whose expression varies during the day because of CLOCK/BMAL1 activation and PER/CRY inhibition.	[2,3]
CDK/cyclin complexes	PER1 interacts with the checkpoint kinase Chk1 and controls the p16-INK4A gene, an inhibitor of CDK/cyclin complexes. c-Myc expression (controlled and inhibited by CLOCK/BMAL1 and stabilized by PER1), inhibits the expression of p21, another inhibitor of CDK/cyclin complexes.	[2,3]
Mechanisms of DNA repair
Mismatch repair (MMR) Double-strand breaks (DSBs)	Indirectly influenced by the clock as both occur during replication.	[33,36]
Nucleotide excision repair (NER)	Directly regulated by the clock through the repair factor XPA.	[36,39,40]
Mitochondrial dysfunction
BMAL1 knockout mice	Low levels of some mitochondrial fusion proteins.	[43]
PER1/2 knockout mice	Altered mitochondrial respiration.	[44]
Reprogramming of metabolism
Pancreas	Pancreatic differentiation is regulated by the biological clock through Wnt and Notch pathways and the cell cycle.	[48]
	Misaligned meals uncouple insulin and corticosterone rhythms contributing to pancreas-associated conditions.	[49]
	Alterations in sleep habits are associated with high levels of Haemoglobin A1c (HbA1c) in young people with type 1 diabetes and with increased insulin requirements.	[49]
The immune system
Sleep period	Highest quantity of undifferentiated T lymphocytes and NK cells.	[52]
	Highest levels of proinflammatory cytokines (such as IL-1β and TNF-α).	[52,53]
Active period	Highest levels of anti-inflammatory cytokines (such as IL-4 and IL-10).	[52,53]
	Glucocorticoids, potent immunosuppressants, peak secretion. For example, cortisol levels are higher in the morning.	[51]