Introduction
Modern electric lighting practices have facilitated a society in which people may work, sleep, and receive goods and services at any time of the day. People are exposed to ill-timed, unnatural, electric light (such as light at night, or “LAN”) through lifestyle choices, necessity, the locations of their residences, and employment during the night shift. As light is the critical regulator for circadian rhythms, exposure to LAN can cause circadian disruption, which can be associated with potential adverse health effects such as cancer. Night shift work includes exposure to electric LAN, sleep disturbances, or changes in meal timing, as well as other potential factors (e.g., social stressors, lifestyle behaviors, decreased exposure to sunlight, and lower vitamin D levels). Most, but not all, of these factors can lead to circadian disruption.
Methods
The National Toxicology Program (NTP) conducted cancer hazard assessments for two exposure scenarios: night shift work and exposure to LAN. We used systematic review methods to identify studies, evaluate study quality, and integrate evidence across studies. Using established criteria, we reached conclusions regarding the strength of the evidence from cancer epidemiology studies for night shift work, exposure to outdoor and indoor LAN, and transmeridian travel. Because circadian disruption is a key intermediate in the pathway between exposure and potential cancer, for each exposure scenario, we used a triangulation approach to integrate the evidence from the cancer studies with evidence from studies of exposure and circadian disruption and studies of circadian disruption and cancer. Our assessment also included mechanistic studies of each exposure scenario and key characteristics of carcinogens. Lastly, based on the totality of the evidence, we placed the cancer hazards into context by specifically defining the circumstances by which night shift work or LAN may cause cancer.
Results and discussion
Night Shift Work: Human epidemiology studies provide strong (but not sufficient) evidence that persistent night work (i.e., frequent and long-term night shift work, or working a large number of night shifts over a lifetime, especially in early adulthood) causes female breast cancer. Evidence that persistent night shift work causes prostate cancer is considered limited. Cancer studies in experimental animals found that simulated shift work or chronic jet lag promotes the growth of mammary-gland and other types of tumors in experimental animals. Finally, mechanistic studies in humans and non-humans demonstrated that (1) circadian disruption plays a role in shift-workmediated carcinogenicity, and (2) night shift work is associated with biological effects that are recognized as key characteristics of carcinogens. A strength of the database is that several animal cancer studies also measured biological effects that are associated with circadian disruption or are characteristics of carcinogens, thus providing a link between exposure, intermediate biological effects, and cancer. Some biological effects observed in experimental animals were also observed in night shift workers. NTP concludes overall that there is sufficient evidence for the carcinogenicity for breast cancer based on the collective body of cancer epidemiology and mechanistic studies in humans.
LAN: Evidence to evaluate the relationship between outdoor LAN exposure, indoor LAN exposure, and transmeridian travel and human cancer from epidemiology studies alone was considered inadequate. However, toxicological and mechanistic studies in experimental animals of modeled LAN provide strong evidence that LAN promotes proliferation and growth of human breast cancer implants, promotes proliferation of other types of cancer, causes biological effects (collective evidence) that are identified as characteristics of carcinogens and that the effects are mediated in part by circadian disruption. The animal studies demonstrate that melatonin suppression (a biomarker of circadian disruption) plays a direct role in LAN-mediated mammary tumor or breast carcinogenicity. Studies in humans demonstrate that exposure to LAN causes melatonin suppression.
NTP final cancer hazard conclusions
There is high confidence for a causal relationship between human cancer (breast and less so prostate) and persistent night shift work — i.e., frequent and long-term night shift work, especially beginning in early adulthood — that causes circadian disruption. This conclusion is based on sufficient evidence of carcinogenicity from the collective body of evidence from cancer epidemiological studies and mechanistic studies in humans and in experimental animals. The strongest evidence is for breast cancer.
There is moderate confidence for a causal relationship between human cancer and certain lighting conditions — i.e., excessive LAN exposure combined with insufficient daylight exposure — that cause circadian disruption. This conclusion is based on strong evidence that LAN acts through mechanisms that are likely to cause cancer in humans.
National Toxicology Program (NTP). 2021. NTP Cancer Hazard Assessment Report on Night Shift Work and Light at Night. Research Triangle Park, NC: National Toxicology Program. https://doi.org/10.22427/NTP-CHR-NSWLAN