The Role of Glucocorticoid Receptor in the Racial/Ethnic Disparity of Aggressive Breast Cancer
thesisposted on 2015-10-21, 00:00 authored by Umaima Al-Alem
Breast cancer is the most common malignancy and the second leading cause of cancer-related death in women worldwide. There is a well-documented variation in breast cancer incidence and mortality across nations and among racial/ethnic groups within these nations. In the United States, the incidence of breast cancer is lower among African American and Hispanic women when compared with white women, yet, as a group African American and Hispanic women have a more aggressive disease at diagnosis and worse survival outcomes. The reasons for racial disparity in breast cancer mortality are largely unknown but likely multifactorial involving environmental and biological factors. A number of epidemiological studies have shown that the cellular alterations resulting from chronic psychosocial stress may increase breast cancer development and progression. One of the primary mediators of stress is glucocorticoid. Glucocorticoid is a steroid hormone with a physiological and pathological role in the body; it acts via its cytoplasmic receptor, the glucocorticoid receptor (GCR). Upon binding to glucocorticoid, GCR is activated and released from a chaperone complex. Activated GCR travels to the nucleus to regulate a myriad of physiological processes such as mammary development and differentiation, inflammation, apoptosis as well as glucose and fatty acid metabolism-processes which have been associated with breast cancer development and progression. The main hypothesis is that alterations in the level or localization of GCR might interfere with the glucocorticoid response, resulting in aberrant downstream cellular responses such as decreased apoptosis and chronic inflammation that might contribute to aggressive breast cancer. And if these characteristics vary by race/ethnicity then this may play a role in the pathogenesis of the racial/ethnic disparity of breast cancer. The overarching theme of this research is to understand the role of GCR in breast cancer and its potential involvement in racial/ethnic disparities. To answer our research question, we used data from the Breast Cancer Care in Chicago (BCCC), a large, multiethnic population of incident breast cancer cases between the ages of 30 and 79 with stored biological samples and linked clinical, genetic ancestry and sociodemographic data.