LIGHT AT NIGHT - CANCER RISKS OF SHIFT WORK

摘要

The risk of breast cancer is several timeshigher in industrialized societies than in developing countries and at least 50percent of breast cancer remains unexplained by known risk factors. It has been proposed that light at night is a risk factor for breast cancer by virtue of its ability to suppress the pineal gland production of the oncostatic neurohormone melatonin. Support for this postulate comes from studies showing that women who work night shifts and are exposed to light at night are at a significantly increased risk of developing breast cancer. Some evidence also indicates that the risk of colorectal cancer is also elevated in female shift workers. The risk of breast cancer is lower in women who either are blind, sleep nine or more hours per night or produce higher levels of melatonin. We have experimentally tested the light at night hypothesis on tumor growth and metabolism in nude rats implanted with tissue-isolated human breast cancer xenografts. Exposure of rats bearing human breast cancer xenografts results in both a dose-dependent decrease in circulating melatonin levels and a concomitant dose-related increase in tumor growth and metabolism. In other studies on rats with human breast cancer xenografts, tumors perfused in situ with melatonin-deficient whole blood collected during midday from healthy, premenopausal women demonstrated robust proliferative activity and metabolism. Xenografts perfused with melatonin-rich blood collected from subjects during the night under total darkness exhibited markedly suppressed proliferative activity and metabolism. Xenografts perfused with melatonin-deficient blood collected after a short exposure (90 minutes) of volunteers to bright, fluorescent white light (2800 lux at eye level) revert to the daytime pattern of high proliferative and metabolic activity. These results provide the first experimental evidence that light at night is a new risk factor for human breast cancer and that melatonin suppression by light at night may be one rational biological explanation for elevated breast cancer risk in female night shift workers. Future research will address whether other melatonin-sensitive cancers are similarly affected by light at night. Other mechanisms involving disruption of the central circadian system, other than melatonin suppression by light at night, may also play an important role in the increased cancer risks posed by shift work.