A Primary Role for the Circulatory Microenvironment in African American Prostate Cancer Disparities?
Abstract
The incidence of prostate cancer (PCa) has increased markedly over the last decades and is the second most prevalent noncutaneous cancer in males in developed regions of the world. In the United States, PCa is the most frequently diagnosed cancer in men, with 268,490 estimated new cases in 2022. It is also the second most common cause of cancer deaths in men, exceeded only by lung cancer, with 34,500 estimated deaths in 2022. However, the risk factors associated with PCa remain to be elucidated. The only firmly established risk factors for PCa are age, family history, and race/ethnicity. Notably, African Americans have among the highest PCa incidence and mortality. The striking population disparities in cancer risk and survival outcomes are borne out of current health statistics data. Black U.S. males are 1.4 to 1.7 times more likely to develop PCa, and 1.7 to 2.2 times more likely to die from this disease compared to their White counterparts. Although PCa was originally thought to be uncommon in subequatorial Africa, it is increasingly apparent that, as the average age of central and west-African populations increases, PCa is becoming more common. As of 2020, sub-Saharan Africa and the Caribbean suffered some of the highest PCa mortality in the world with rates ranging from 22.0-27.9 deaths per 100,000, which is in line with the African American population of 37.9 deaths per 100,000. Based on epidemiological studies, several hypotheses brought forward to explain these disparities include cultural, access to health care, diet, systemic racism, residential segregation leading to exposure of environmental pollutants and chemical carcinogens, and/or socioeconomic stressors, to name a few. In addition to these features, a growing body of biological and genetic evidence suggests that genetic polymorphisms and aberrant gene expression are important influences predisposing or contributing to the disparities of cancer incidence and mortality. While intriguing, these findings have been association-based (‘guilt by association’), and direct causal links of the candidate genes to cancer health disparities remain to be firmly established. Another possible contributing factor to PCa disparities in the African American population is the immediate environment surrounding the primary tumor, known as the microenvironment. The primary tumor’s microenvironment contains a variety of components such as immune cells, fibroblasts, blood vessels and extracellular proteins that can interact with tumor cells to modify the behavior of the tumor cells. Research has demonstrated that these interactions may be different in African American’s with PCa, potentially leading to a more aggressive cancer. In addition to the surrounding microenvironment of the primary tumor, there is another microenvironment that has received less attention, specifically the circulatory microenvironment comprised of platelets that encounter and communicate with circulating tumor cells. While platelets are primarily known for their cardiovascular role in blood clotting, increasing evidence points to their critical role in cancer progression and mortality. Our early findings indicate that the interactions of platelets and PCa cells are different in the African American population compared to the European American population. The objectives of this application is to study the interactions of platelets with PCa cells in the two populations, and how differences in these interactions may be contributing to PCa disparities in the African American population.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310409
Entities
People
- Norman Lee
Organizations
- George Washington University
- United States Army