Defense Date
2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Epidemiology
First Advisor
Juan Lu
Second Advisor
Hua Zhao
Third Advisor
Bernard F. Fuemmeler
Fourth Advisor
Lisa S. Shock
Abstract
Introduction: Breast cancer is the most common cancer among women in the United States, accounting for approximately 31% of all cancers. Breast cancer is also one of the leading causes of cancer death in women. Animal studies show a link between stress and breast cancer. However, to date, epidemiological evidence on the relationship between chronic stress and breast cancer risk is mixed. This is at least partially due to weaknesses in traditional research, which include: 1) questionnaires that rely on subjective recall bias; 2) underestimation of individual resilience; and 3) lack of objective biomarkers representative of chronic stress. Therefore, we will use allostatic load (AL), a novel complex index involving cumulative physiological losses across multiple systems to assess the role of chronic stress in breast cancer carcinogenesis.
Methods: AL was a new field in breast cancer. Three independent studies were used to help comprehensively explore the role of AL in breast cancer carcinogenesis. The first study (Chapter 2) to assess the effect of lifestyle factors and socioeconomic status on AL in women. Next, we investigate the association between chronic stress and breast cancer risk using AL. Finally, we further explore molecular changes and differentially expressed genes associated with AL and consider the potential mechanisms through which AL impacts breast cancer tumorigenesis.
Results: The first study demonstrates that age, race, socioeconomic status, and lifestyle factors can increase AL over time. Thus, promoting a healthy lifestyle could slow the AL growth rate over time, reduce chronic stress, and improve overall health. The second study demonstrated that higher AL was associated with an increased breast cancer risk in women. This association is likely independent of known breast cancer risk factors. Thus, AL could be a valuable biomarker to help predict breast cancer risk and stratify patients. The third study identified a panel of genes significantly associated with AL. In further pathway analysis, significant relationships between AL and immune function were observed. These findings provide valuable information to elucidate the mechanisms behind different stress levels.
Conclusions: These analyses help us understand the risk factors that affect AL and the potential mechanisms by which high AL leads to breast cancer carcinogenesis. AL could be a valuable biomarker to help breast cancer risk prediction and stratification.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-8-2024