Disruption of the Molecular Circadian Clock and Cancer: An Epigenetic Link.

The circadian clock is regulated at the molecular level by feedback circuits of a group of genes known as "clock genes", which establish a mechanism that controls circadian cellular physiology to maintain the balance between cell proliferation, response to DNA damage and apoptosis. Alterations in the expression of clock genes due to genetic or epigenetic mechanisms have been associated with multiple diseases including cancer. Even some clock genes such as the Per1, Per2, Bmal1 genes have been proposed as tumor suppressor genes, with a relevant role during carcinogenesis. At the molecular level, multiple mechanisms of molecular control have been described to link circadian transcription, cell cycle control, and tumorigenesis. In addition, recent findings describe an epigenetic control of circadian transcription, at the level of DNA methylation as well as in the modifications of histones. However, the link between the circadian epigenome and cancer remains unclear. In this article, we review the evidence that suggests a relationship between alterations in the expression of clock genes, with the development of cancer, from the epigenetic landscape.