O8A.2 Breast cancer and persistent night shift work starting at an early age that causes circadian disruption

Over 10 million U.S. adults and ∼15%–20% worldwide work night shifts. Shift work, a complex exposure scenario, can cause circadian disruption (CD) and possible adverse health effects such as breast cancer. Although there have been a plethora of meta-analysis on shift work and breast cancer, these are not very informative because of inconsistent definition of shift work across studies. The U.S. National Toxicology Program (NTP) conducted a systematic review (SR) to determine whether night shift work should be listed in the Report on Carcinogens (RoC). The SR included a review of cancer epidemiology studies and mechanistic studies of CD and cancer. NTP developed a protocol, based on scientific input gathered during a public workshop, which identified key issues for conducting the SR: definition of surrogates of night work related to CD, inclusion of multiple metrics of night work, information on early age at exposure when breast tissue is most susceptible, cancer subtypes, effect modifiers and confounders, and cohort truncation. Up to three reviewers evaluated the potential for bias and study sensitivity of each of the 26 cohort and case-control studies considered in the assessment, with five excluded due to exposure assessment concerns. To reach an overall conclusion, findings were integrated across studies, considering factors listed above and confidence in the evidence from each study. 11 of 13 most informative studies and 6 of 8 less informative night shift work studies found increased risks of breast cancer related to night shift work. Excess risks were found mainly among women working frequent nights for long durations starting at an early age (e.g., persistent night shift work). Mechanistic data provided evidence that night shift work causes CD, which plays a major role in its carcinogenicity. In conclusion, NTP recommends that persistent night shift work that causes CD be listed in the RoC.