Markers of Circadian Disruption and Reproductive Risk Factors for Breast Cancer

Background: Circadian disruption is hypothesized to impact reproductive signaling, which in turn has long been linked to breast cancer. The melatonin hypothesis holds that increased exposure to artificial light at night and resulting inhibition of nocturnal melatonin may account for recent increased breast cancer incidence. Coregulation of melatonin, circulating reproductive hormones and precursor gonadotropins has been well documented in animal models, particularly those of seasonal breeders, yet elucidation of these complex hormonal relationships in humans has proven challenging. This work investigates the link between circadian disruption and female gonadal activity and reproductive-related outcomes in the context of breast cancer risk. Methods: We examined the association between rotating shift work and age at menopause among the Nurses' Health Study II cohort, estimating cause-specific hazards using proportional hazards models with time-dependent covariates. The cross-sectional associations between nocturnal melatonin production, menstrual cycle length and circulating sex steroid hormones and prolactin were examined in two additional populations using ordinary least squares regression and generalized estimating equations. Effect modification of nocturnal melatonin and prolactin by age and diurnal preference was additionally investigated. Results: The hazard of natural menopause was observed to be lower in women who had worked >10 years of rotating shifts since baseline (HR: 0.76; 95% CI: 0.69-0.85), in the direction of our hypothesis. The strength of this effect was not maintained upon inclusion of prior exposure. Nocturnal melatonin levels were not found to be associated with menstrual cycle length, nor with daytime circulating levels of estradiol, progesterone or prolactin. However, we observed effect modification of nocturnal melatonin and circulating daytime prolactin by age. Conclusion: Our findings do not conclusively support or refute an association between circadian disruption and reproductive risk factors for breast cancer. Future work will benefit from more precise measurement and observation of the interplay between endocrine markers of circadian activity and reproductive function over time.

Department dc:contributor.department

Dalla Lana School of Public Health

Year dc:date.issued

2015

Author dc:creator

• Stock, David

Advisor dc:contributor.advisor

• Knight, Julia A

• breast cancer
• circadian disruption
• gonadal activity
• melatonin
• night work
• prolactin

Handle dc:identifier.uri

http://hdl.handle.net/1807/69515

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/69515