A Precision Medicine Study of How Inflammation May Underlie the Excessive Burden of Prostate Cancer in Men of African Ancestry
Abstract
Not all segments of the U.S. population have equally benefited from the advances in our knowledge and treatment of cancer. As one example, men of African descent continue to experience a disproportionately high prostate cancer mortality. We and others described differences in tumor biology and chronic inflammation between African American and European American prostate cancer patients. We also found that the anti-inflammatory drug, aspirin, reduces the risk of aggressive prostate cancer and disease recurrence in African American men. The findings indicate that African American prostate cancer patients may have an increased occurrence of an inflammation that is associated with their disease and promotes disease progression. Chronic inflammation has been described as a prostate cancer risk factor that is related to a more aggressive disease. Yet very few studies have assessed the origin and disease-promoting effects of a systemic inflammation when prostate cancer develops among high-risk men. For example, is the observed inflammation a tumor-specific event or is it a systemic inflammation, and how does it affect disease progression in African American men? Moreover, inherited and lifestyle factors may increase the risk of a systemic inflammation in these men. Based on this information, we set out to investigate whether a systemic inflammatory process defined by elevated immune-inflammation markers is related to African ancestry or other genetic factors, lifestyle factors, and aggressive disease. We will also analyze the tumor biology of these men to obtain an understanding of the causes (e.g., acquired mutations versus lifestyle) and effects of the immune-inflammation signature in these tumors. We will analyze blood samples and DNA from the National Cancer Institute (NCI) Maryland Prostate Cancer Case-Control Study and the NCI Ghana Prostate Study, totaling 1,500 cases and 1,500 controls and bringing together 900 African American, 900 European American, and 1,200 African men. Clinical information has been collected for all cases. We will measure 92 immune-inflammation markers, as well as additional markers related to infection and inflammation signaling in blood samples from these men. We will also obtain information about their omega-3 fatty acid levels, which are essential fatty acids and antioxidants, from measurements, as well as data about their lifestyles from completed questionnaires, enabling us to conduct a comprehensive investigation of systemic inflammation and its relationship to a man’s ancestry, lifestyle, and prostate cancer risks. Moreover, we will perform a genetic analysis to evaluate the genetic basis of differences in immune-inflammation markers among men with prostate cancer and men without the disease. Lastly, our proposal will examine both tumors and blood from 50 African American, 50 European American, and 150 Nigerian men. Here, we will study differences in inflammation status and tumor biology between these men to determine how these differences may relate to genetic changes in these tumors. Our study will be the first to explore the relationship between systemic/chronic inflammation, ancestry, and tumor biology as a cause of prostate cancer progression in men of African descent. Creating an awareness of how the interaction between chronic inflammation and tumor biology affects prostate cancer progression in a high-risk population like African American men offers the opportunity to develop improved prevention and therapeutic strategies to decrease the disease burden among all men. As an immediate impact of our study, clinicians could be encouraged to recommend the use of anti-inflammatory drugs, a low-cost treatment with potentially high benefit, to African American men who either have developed prostate cancer or are at a high risk for the disease to reduce the risk of an aggressive or recurrent disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810589
Entities
People
- Clayton Yates
Organizations
- Tuskegee University
- United States Army