Abstract 106: Assessing the impact of staggered light exposure on breast cancer risk and metabolism

Abstract

Abstract Background: Numerous epidemiological studies, including the Nurses' Health Study II, found that shift workers have a higher risk for breast cancer. These studies hypothesize that suppressed melatonin and disrupted clock gene expression likely lead to an immune compromised, proliferative phenotype. However, the majority of studies to date rely on correlative evidence. With the onset of the COVID-19 pandemic, shift work has become increasingly prevalent, making the need to understand the mechanisms promoting disease, including breast cancer, even more important. Objective: The objective of this study is to analyze the impact of staggered light exposure on the immune function and breast tissue gene expression in order to identify how breast cancer risk is mediated. Methods: An 18-week study with 10 C57BL/6 female mice was conducted whereby half of the mice were exposed to a staggered light/dark (LD) cycle, as would be experienced by shift workers, and half were exposed to a regular LD cycle. Body weight was monitored weekly and sera and mammary tissues were collected at termination. The sera from each group was pooled and cytokine levels assessed using an antibody-pair-based assay. Results: Intriguingly, although the mice from the two study groups did not significantly differ in average body weight, the staggered LD exposure group had higher levels of inflammatory cytokines indicative of chronic, low-grade inflammation. Notably, the staggered LD group had 75% higher IL-6 levels, 157% higher IL-10 levels, and 49% higher TNF-alpha levels compared to the control group. To determine the impact of staggered light exposure on localized breast tissue gene expression, qPCR arrays of breast cancer risk and inflammatory genes will be done comparing expression levels between the control and staggered LD groups. IHC techniques will be used to determine Ki67 and macrophage subtype infiltration in the breast tissue of the two groups. Conclusion: Our data show that staggered LD exposure induces chronic, low-grade inflammation independent from body mass, which can be indicative of increased breast cancer risk. These data help elucidate the metabolic and immune responses induced by staggered light exposure, helping to define the mechanisms promoting health risks imposed by shift work, with the ultimate goal to develop preventive measures to limit breast cancer development. Citation Format: Lauren Palluth, Brittany Harlow, Bryan McCellan, Christopher Jolly, Molly Bray, Linda deGraffenried. Assessing the impact of staggered light exposure on breast cancer risk and metabolism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 106.