Abstract A010: Association of allostatic load and overall cancer risk among women during the menopausal transition. [R]
Authors: Shen Jie , Zhao Hua , Fuemmeler Bernard , Guan Yufan 
Published: January 2023

Chronic stress and biological aging are closely related, and both associated with mitochondrial dysfunction, abnormal DNA methylation, telomere shortening, failed allostasis, accumulated reactive oxygen species (ROS), etc. For example, allostatic load (AL), a biomarker of chronic stress, increases with age as a result of the cumulative effects of allostasis across the lifespan. In US, minority populations have accelerated aging that results from chronic exposure to lifetime stressors and unhealthy behaviors. Elevated chronic stress is thought to increase cancer risk, though the results so far have been inconsistent, and the underlying mechanism remains unclear. In this study, we carried out the first study to evaluate the relationship between allostatic load (AL), a biological indicator of chronic stress, and overall cancer risk in a multi-ethnic women cohort, including 3015 women who participated in the Study of Women’s Health Across the Nation (SWAN). Based on the distribution of AL, the study population was categorized into four groups, from the lowest (1st category) to the highest AL group (4th category). At baseline, Black women and Hispanic women were more likely to be in the higher AL categories than White women (p &lt; 0.001). In addition, women who smoked regularly, drank alcohol regularly, had no leisure physical activity, and had restless sleep were also more likely to be in the higher AL categories than their relative counterparts (p &lt; 0.001). We also observed that women in the lower-income category with no health insurance were more likely to be in the higher AL category (p &lt; 0.001). The study then found that women in the 4th category of AL (the highest AL group) had a 1.64-fold increased risk of overall cancer (Hazard ratio (HR): 1.64, 95% confidence interval (CI): 1.04, 2.59). The risk association was further strengthened after adjusting demographics, health behaviors, and socioeconomic factors with an HR of 2.08, suggesting that at least partially, AL may reflect the biological pathways linking those common cancer risk factors and cancer development. In further analysis of individual biomarkers of AL score, we found that higher levels of triglyceride and CRP were associated with increased risk of cancer, highlighting the role of metabolic dysfunction and inflammation in the etiology of cancer development. In summary, our study indicate that AL may be a useful biomarker predictive of cancer risk. Findings from our study contribute essential knowledge to the role of chronic stress and its biomarker, AL, in the etiology of cancer development. Furthermore, AL has potential to serve as target for novel interventions and biomarker for stress reduction-based cancer prevention.

Citation Format: Jie Shen, Hua Zhao, Bernard Fuemmeler, Yufan Guan. Association of allostatic load and overall cancer risk among women during the menopausal transition. [R] [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr A010.