0040 Associations of Waist Circumference to DNA Damage in Night Shift Workers

Abstract Introduction The association between body composition and chronic diseases, including certain cancers, is well established. Abdominal adiposity, measured clinically as waist-to-hip ratio, has a strong predictive value for disease development independent of body mass index (BMI). Circadian disturbance exacerbates adiposity-related risk of disease, disproportionately affecting night-shift workers. Though it is understood that circadian disturbance can lead to increased genotoxicity−and subsequent cancer risk−the influence of body composition is poorly understood. Here, we evaluate associations between waist-to-hip ratio, BMI, and shift-work status to DNA damage in immune cells. Methods Non-rotating workers, 15 day-shift (DS) and 15 night-shift (NS) (aged 30-55; 16 females), participated in a controlled, 24-hour laboratory study immediately following their typical workweek. Waist-to-hip ratio and BMI were recorded prior to the study. The laboratory environment involved continuous behavioral monitoring and sustained wakefulness. Peripheral blood mononuclear cells (PBMCs) were collected every 6 hours via intravenous catheter. An alkaline comet assay (CometChip, Cell Array) was used to quantify DNA damage in 1153−4738 PBMCs per participant using comet scoring software (CometScore, Trevigan), providing the percent tail DNA (i.e. total percentage of damaged DNA compared to undamaged DNA). Results T-tests revealed no significant difference between DS and NS workers’ waist-to-hip ratio (t(23)=−0.18, p=0.86) or BMI (t(28)=−1.06, p=0.30). Pearson’s correlations showed that waist-to-hip ratio was strongly associated with DNA damage in NS workers (r=0.79, p< 0.001), but BMI was not (r=0.42, p=0.12). In DS workers, there was no significant correlation between DNA damage and waist-to-hip ratio (r=0.45, p=0.19) or BMI (r=−0.15, p=0.58). Conclusion Our findings are consistent with data showing a relationship between increased waist-to-hip ratio and DNA damage/reduced repair mechanisms in PBMCs, which increases genomic instability and is a hallmark of cancer. However, this was only the case for long-term NS workers, further implicating central adiposity as a risk factor for developing certain cancers in individuals exposed to circadian disturbance. Future research should determine other factors associated with DNA damage in this population. Support (if any) BCS: Andy Hill CARE Fund & Health Sciences and Services Authority of Spokane County; SG: NIH award R01ES030113.