Night-shift work, CLOCK gene and risk of endometriosis

University Of Washington, Seattle WA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Endometriosis, which affects approximately 5 - 10% of U.S. reproductive-age women with chronic pelvic pain, dysmenorrhea, infertility, and increased cancer risk, has been linked in epidemiologic studies to exposures indicating high circulating estrogen levels. One such exposure may be night-shift work, which has been associated with increased risk of two other estrogen-mediated diseases, breast cancer and adverse coronary events. Serum free estrogen secretion has a daily (circadian) rhythm in humans. Human circadian rhythms are controlled by a central master clock in the suprachiasmatic nuclei (SCN) in the hippocampus; this clock is controlled by complex feedback loops ultimately controlled by differential gene expression and modified by external time cues. The SCN contains estrogen receptors, suggesting that estrogen feeds back into clock control in females. We propose the first large-scale U.S. epidemiologic study to determine whether endometriosis is associated with night-shift work and/or with a genotype previously found to be related to human circadian rhythm disruption, the T3111C polymorphism of the human CLOCK gene. The proposed study will be an ancillary investigation to the Women's Risk of Endometriosis study. [unreadable] [unreadable]