Light at night, shiftwork, and breast cancer risk.

Breast cancer is the most commonly diagnosed female noncutaneous cancer in the United States and in Europe. The etiology of breast cancer is primarily unknown, with an estimated one quarter of all breast cancers possibly due to heritable factors (1) and only a minor proportion possibly due to already established environmental risk factors, such as early age at menarche, older age at first pregnancy, and delayed menopause (2). Because the incidence of breast cancer in many countries is increasing, for unclear reasons, it is not surprising that society is demanding explanations for the increased incidence of the disease and that researchers are searching for new causes. One avenue of research has been the so-called “man-made endocrine disrupting chemicals,” such as 2-(chlorphenyl)-2-(4-chlorphenyl)-1,1,1-trichlorethan (DDT), polychlorinated biphenyls, or nonyl phenols (3). So far, however, the results from this research have been sparse in expanding our knowledge about risk factors for breast cancer. In this issue of the Journal, two independent epidemiologic studies by Davis et al. (4) and Schernhammer et al. (5) have provided evidence about another potential risk factor, light at night. These studies (4,5) support a hypothesis published about 10 years ago by the former group that light at night may be a potential risk factor of breast cancer (6,7). The scientific rationale behind this intriguing hypothesis is that exposure to visible light, including artificial light, suppresses the normal nocturnal production of melatonin by the pineal gland (6). Melatonin is a mammalian hormone involved in circadian rhythms and sleep and potentially in restraining tumor growth (8). The synthesis and release of melatonin occur in a dose–response-like manner that is stimulated by darkness and inhibited by light through photic information from the retina. Peak melatonin levels normally occur during sleep in the middle of the night (8). Several experimental studies have provided evidence of an association between melatonin levels and risk of cancer. For example, evidence from rodent studies found that pinealectomy increased tumor growth (9), that administration of melatonin inhibited the promotion of chemically induced mammary tumors (9,10), and that constant light exposure had a growth-promoting effect on chemically induced tumors (11). Evidence in humans is less direct, although impaired pineal secretion of melatonin is associated with an increased release of estrogen by the ovaries (7,8), and low serum melatonin concentrations have been reported in women with estrogen receptorpositive breast cancer (8). In vitro, physiologic concentrations of melatonin inhibited the growth of human breast cancer cells