Circadian Disruption and Breast Cancer: From Melatonin to Clock Genes

Stevens, Richard G.

Epidemiology:
doi: 10.1097/01.ede.0000152525.21924.54
Hypothesis Paper
Abstract

The global impact of breast cancer is large and growing. It seems clear that something about modern life is the culprit, yet there is thus far a lack of satisfactory explanations for most of the increases in risk as societies industrialize. Support has developed for a possible role of “circadian disruption,” particularly from an altered-lighted environment (such as light at night). Lighting during the night of sufficient intensity can disrupt circadian rhythms, including reduction of circulating melatonin levels and resetting of the circadian pacemaker of the suprachiasmatic nuclei. Reduced melatonin may increase breast cancer risk through several mechanisms, including increased estrogen production and altered estrogen receptor function. The genes that drive the circadian rhythm are emerging as central players in gene regulation throughout the organism, particularly for cell-cycle regulatory genes and the genes of apoptosis. Aspects of modern life that can disrupt circadian rhythms during the key developmental periods (eg, in utero and during adolescence) may be particularly harmful. Epidemiologic studies should consider gene and environment interactions such as circadian gene variants and shift work requirements on the job.

Author Information

From the Department of Community Medicine, University of Connecticut Health Center, Farmington, Connecticut.

Submitted 4 May 2004; final version accepted 15 November 2004.

Supported by grant R21ES11659 from the National Institute of Environmental Health Sciences.

Correspondence: Richard G. Stevens, Department of Community Medicine, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030-6325. E-mail: bugs@neuron.uchc.edu.

© 2005 Lippincott Williams & Wilkins, Inc.