Metabolomic and Methylation Pathways Associated with Black-White Disparity in Lethal Prostate Cancer
Abstract
African American men (AA) have long been known to have higher occurrence and death from prostate cancer (PCa), and this disparity continues to the present. AA men have a 75% higher rate of developing PCa and are twice as likely to die from it as European American (EA) men. The stark fact is that the twofold higher death rate for AA men has been apparent for at least 50 years, yet we still don’t understand the biological underpinnings for the PCa disparity. The disparity is likely to be the result of many factors, including nonbiological factors, such as access to medical care, education level, income; exposure and lifestyle factors such as diet, obesity, physical activity, and environmental exposures; and biological factors such as genetics and metabolism. Many research studies have shown that even after taking account of differences in the non-biological factors, the disparity in PCa death remains, suggesting that important biological factors remain to be identified. Considerable research has identified differences between AA and EA men with PCa in the genetic characteristics and the products of genetic activity, i.e., RNA and proteins. However, those characteristics don’t tell us enough about what is actually happening in the prostate cancer cells, which is where the biological machinery affecting the cancer’s behavior takes place. A potential way to gain further knowledge that may take us closer to the mechanisms affecting PCa in AA and EA men is to analyze the metabolomics of these two groups. Metabolomics is the study of patterns of metabolites in tissues and body fluids. Because metabolites reflect the biological activities taking place in the cells they may provide us with more direct information about differences in prostate tumors arising in AA and EA men. One important aspect of metabolomics is as a regulator of epigenetic activity. Epigenetics refers to modification of the activity of genes when one or more methyl groups – a small chemical compound of carbon and hydrogen – either bind to or are removed from areas in genes that can turn the genes on or off. These methyl groups are derived from specific metabolites. Because of the close interaction between metabolomics and epigenetics, our objective is to evaluate differences in metabolomics and epigenetic patterns in AA and EA men, half of whom will have developed biochemical recurrence after prostatectomy (BCR; rise in PSA indicating cancer remains), and half of whom will not have developed BCR. We will measure metabolomics and epigenetic patterns in prostatic fluid, which is secreted by the prostate from the ducts where prostate tumors actually begin. Because this fluid is closer to the biology of the prostate than other accessible body fluids like blood or urine, it should provide stronger signals of the biology in AA and EA men. Because BCR is the first sign that a man may not have been cured by his prostatectomy, it is a precursor indicating the man is at increased risk for metastasis and death. By studying the metabolomics and epigenetic differences that may contribute to the higher PCa death rates in AA men, we are addressing one of the FY20 PCRP Health Disparity Award Focus Areas: biological contributors, such as genetic and genomic differences, which can be associated with disparate outcomes in patient populations. Metabolomics can be viewed as the end product of a biological chain of events: genes are transcribed to messenger RNA, which in turn provides the genetic code to build proteins, which are broken down into amino acids, which form metabolites, which then affect the functioning of cells. Thus, identifying differences in metabolomics and epigenetics patterns associated with increased BCR in AA men may, in the short term (next 3–5 years), provide new hypotheses for the racial disparity in PCR death. A key advantage is that patterns of metabolomics and epigenetic activity can be modified. Diet, physical activity, and some com
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110373
Entities
People
- Bruce J Trock
Organizations
- Johns Hopkins University
- United States Army