Circadian disruption and breast cancer: an epigenetic link?

Abstract

Breast cancer is already the most common malignancy affecting women worldwide, and evidence is mounting that breast cancer induced by circadian disruption (CD) is a warranted concern. Numerous studies have investigated various aspects of the circadian clock in relation to breast cancer, and evidence from these studies indicates that melatonin and the core clock genes can play a crucial role in breast cancer development. Even though epigenetics has been increasingly recognized as a key player in the etiology of breast cancer and linked to circadian rhythms, and there is evidence of overlap between epigenetic deregulation and breast cancer induced by circadian disruption, only a handful of studies have directly investigated the role of epigenetics in CD-induced breast cancer. This review explores the circadian clock and breast cancer, and the growing role of epigenetics in breast cancer development and circadian rhythms. We also summarize the current knowledge and next steps for the investigation of the epigenetic link in CD-induced breast cancer.

Keywords: breast cancer; circadian disruption (CD); circadian rhythms; epigenetics; melatonin (MLT).

Figure 1. Overview of the two interlocking circadian clock regulatory feedback loops

The blue arrows represent the BMAL1/CLOCK regulatory feedback loop which controls the expression of the Per and Cry genes. The orange arrows represent the regulatory feedback loop that controls the expression of the Bmal1 gene and formation of the BMAL1/CLOCK heterodimer.