Light and melatonin
Light at night is an environmental exposure that has become integral to our lives. Before 1879, when the light-bulb was invented, humans were exposed to only insignificant amounts of low-intensity light at night from sources such as candles and petroleum lamps. Later on, paralleled by growing industrialisation, a need for longer days emerged, with electric light making it possible to push multifaceted working schedules further and further into the night. Today, exposure to light at night, both in the form of occupational exposure during night work and as a personal choice and lifestyle, is experienced by numerous night-active members of our societies. We, however, do not appear to be well adapted to bright nights: shift workers, for instance, reportedly suffer from a variety of health problems (Vener et al, 1989; Costa, 1997; Boggild and Knutsson, 1999). Previously, humans tended to conduct their daily activities according to the sun's cycle: rising at sunrise and going to bed at sunset. Such sleep rhythms appear not only to be more natural, but also to be essential for a variety of physiologic functions in humans, such as body temperature, excretion, and the production of hormones (Weitzman et al, 1981; Czeisler and Klerman, 1999). Melatonin, for example, follows a very distinct pattern of production, which is very closely linked to the individual's circadian rhythm, following light exposure: during the day, almost no melatonin is produced, whereas during the night, when it is dark, almost all melatonin is produced (Snyder et al, 1967). Environmental lighting powerfully alters physiologic release of melatonin, which typically peaks in the middle of the night (Zeitzer et al, 2000): a profound melatonin reduction was observed in humans after 2 weeks of intermittent nightly exposure to light (Zeitzer et al, 2000; Graham and Cook, 2001). While levels may recover during the periods of sleep, they will not recover to their maximal amount unless habits are kept constant, because any disruption of a natural circadian rhythm will diminish the ability to recover from that suppression.
Link between light at night and breast cancer risk through the oestrogen pathway
Past studies suggested that the excess breast cancer mortality seen in urban areas as well as the North East as compared to the South of the US could be due to differences in exposure to sunlight (Garland et al, 1990), perhaps mediated through the vitamin D pathway. However, based on a large body of experimental work in the 1960s and 70s, evidence grew that visible light, including artificial light, can acutely suppress melatonin. Thus, novel hypotheses were generated, proposing that the diminished function of the pineal gland might promote the development of breast cancer in humans. One of the initial theories supporting that a diminished function of the pineal gland might promote the development of cancer hypothesised that melatonin suppression may lead to an increase in levels of reproductive hormones, particularly oestradiol, thereby increasing the growth and proliferation of hormone-sensitive cells in the breast (Cohen et al, 1978; Stevens, 1987).
Observational studies have supported that theory, indicating that women in occupations that expose them to light at night do experience a higher risk of breast cancer, and that blind women, who do not have the ability to experience lower melatonin levels because of their supposed lack of receptivity to light, have a lower incidence of breast cancer (Schernhammer and Hankinson, 2003). Studies fairly consistently report meaningful increases in breast cancer risk among postmenopausal women exposed to shift work (Pukkala et al, 1995; Tynes et al, 1996; Davis et al, 2001; Hansen, 2001; Rafnsson et al, 2001; Schernhammer et al, 2001). Two retrospective studies of flight attendants with occupational exposure to light at night linked the employment time to an increased risk of breast cancer (Pukkala et al, 1995; Rafnsson et al, 2001). Two nationwide record linkage studies (Tynes et al, 1996; Hansen, 2001) and a retrospective case–control study (Davis et al, 2001) associated night work with an approximately 50% higher risk of breast cancer (Tynes et al, 1996; Hansen, 2001). Finally, the Nurses’ Health Study, the only prospective study published that evaluated the association, observed a positive association of extended periods of rotating night work and breast cancer risk (more than 30 years of rotating night work: RR=1.36; 95% CI=1.04–1.78) (Schernhammer et al, 2001). In this study, night work was defined as the total number of years during which the nurses had worked rotating night shifts with at least three nights per month, in addition to days and evenings in that month. During 10 years of follow-up, 2441 incident cases of breast cancer were documented among 78562 women. A positive association between the number of years a woman had worked on rotating night shifts and breast cancer risk was observed (test for trend, P=0.02). Among postmenopausal women, the relative risk for breast cancer, controlling for all the major risk factors for breast cancer, was moderately increased after 1–14 and 15–29 years of rotating night shift work, and was further increased (RR 1.36; 95% CI 1.04–1.78) for those nurses who worked the night shift for 30 or more years, with similar risks for premenopausal women (RR 1.34; 95% CI 0.77–2.33). Thus, in sum, observational studies seem to support the hypothesis that night work increases the risk for breast cancer. This association may be mediated, at least in part, by the oestrogen pathway.
Light at night and other cancers
Only few previous observational studies have addressed the relationship between shift work and cancers, other than breast cancer. Early suggestions for an increased cancer risk related to shift work arose from two mortality studies that were conducted among male shift workers to assess the influence of shift work upon total and cause-specific mortality, with suggestions for an increased cancer mortality related to shift work. Tynes et al report an increased risk of colon (SIR 1.3; 95% CI 0.6–2.6) and rectum cancer (SIR 1.8; 95% CI 0.7–3.9) in their cohort of female radio and telegraph workers. Rafnsson and colleagues do not report the risks for colorectal cancer among the female Icelandic flight attendants, but describe an elevated risk for tumours of the lymphatic system.