Abstract: OBJECTIVES: Growing but limited evidence suggests that night shift work is associated with breast cancer. The authors conducted a nationwide case-control study nested within a cohort of 18,551 female military employees born in 1929-1968 to investigate the risk for breast cancer after night shift work and to explore the role of leisure time sun exposure and diurnal preference. METHODS: The authors documented 218 cases of breast cancer (1990-2003) and selected 899 age-matched controls from the cohort by incidence density sampling. Information on shift work, sun exposure habits, diurnal preference and other potential confounders was obtained from a structured questionnaire. ORs were estimated by multivariate conditional logistic regression. RESULTS: Overall, the authors observed an adjusted OR of 1.4 (95% CI 0.9 to 2.1) among women with ever compared with never night shifts. The RR for breast cancer tended to increase with increasing number of years of night shift work (p=0.03) and with cumulative number of shifts (p=0.02),with a neutral risk for fewer than three night shifts per week. The OR for the group with the highest tertile of cumulative exposure was 2.3 (95% CI 1.2 to 4.6). The most pronounced effect of night shift work on breast cancer risk was observed in women with morning chronotype preference and intense night shifts (OR=3.9, 95% CI 1.6 to 9.5). Night shift workers tended to sunbathe more frequently than day workers. CONCLUSIONS: The results indicate that frequent night shift work increases the risk for breast cancer and suggest a higher risk with longer duration of intense night shifts. Women with morning preference who worked on night shifts tended to have a higher risk than those with evening preference.

Abstract: BACKGROUND: An increased risk of breast cancer has been observed in night shift workers. Exposure to artificial light at night and disruption of the endogenous circadian rhythm with suppression of the melatonin synthesis have been suggested mechanisms. We investigated the hypothesis that rotating night shift work is associated with mammographic density. METHODS: We conducted a cross-sectional study on the association between rotating night shift work characteristics, 6-sulfatoxymelatonin (MT6s) creatinine adjusted in a spot morning urine sample, and a computer-assisted measure of mammographic density in 640 nurses and midwives ages 40 to 60 years. The associations were evaluated using regression models adjusted for age, body mass index, menopausal status, age at menopause, age at menarche, smoking, and the calendar season of the year when mammography was conducted. RESULTS: The adjusted means of percentage of mammographic density and absolute density were slightly higher among women working rotating night shifts but not statistically significant [percentage of mammographic density = 23.6%, 95% confidence interval (CI), 21.9%-25.4% vs. 22.5%, 95% CI, 20.8%-24.3%; absolute density = 23.9 cm(2), 95% CI, 21.4-26.4 cm(2) vs. 21.8 cm(2), 95% CI, 19.4-24.3 cm(2) in rotating night shift and day shift nurses, respectively). There were no significant associations between the current or cumulative rotating night shift work exposure metrics and mammographic density. No association was observed between morning MT6s and mammographic density. CONCLUSIONS: The hypothesis on the link between rotating night shift work, melatonin synthesis disruption, and mammographic density is not supported by the results of the present study. IMPACT: It is unlikely that the development of breast cancer in nurses working rotating night shifts is mediated by an increase in mammographic density.

Abstract: Breast cancer risk is high in industrialized societies, and increases as developing countries become more Westernized. The reasons are poorly understood. One possibility is circadian disruption from aspects of modern life, in particular the increasing use of electric power to light the night, and provide a sun-free environment during the day inside buildings. Circadian disruption could lead to alterations in melatonin production and in changing the molecular time of the circadian clock in the suprachiasmatic nuclei (SCN). There is evidence in humans that the endogenous melatonin rhythm is stronger for persons in a bright-day environment than in a dim-day environment; and the light intensity necessary to suppress melatonin at night continues to decline as new experiments are done. Melatonin suppression can increase breast tumorigenesis in experimental animals, and altering the endogenous clock mechanism may have downstream effects on cell cycle regulatory genes pertinent to breast tissue development and susceptibility. Therefore, maintenance of a solar day-aligned circadian rhythm in endogenous melatonin and in clock gene expression by exposure to a bright day and a dark night, may be a worthy goal. However, exogenous administration of melatonin in an attempt to achieve this goal may have an untoward effect given that pharmacologic dosing with melatonin has been shown to phase shift humans depending on the time of day it's given. Exogenous melatonin may therefore contribute to circadian disruption rather than alleviate it.