Racial Differences in Systemic and Prostatic Inflammation
Abstract
Black men have a 67% higher prostate cancer risk than white men and over twice the mortality. While in general, black men have reduced access to care, within an equal access setting, we found they had higher grade disease at diagnosis and higher risk of cancer recurrence after surgery. These findings suggest underlying biological differences between black and white men. Recent data suggest differences in how the immune system and tumor interact may contribute to the more aggressive disease among black men. It has been postulated inflammation promotes prostate cancer development. Indeed, we and others found aspirin and non-steroidal anti-inflammatory drugs (e.g., ibuprofen) were linked with lower prostate cancer risk. However, the link between inflammation and prostate cancer is more complex. We previously studied PSA (prostate-specific antigen) levels in healthy men (a potential sign of prostate cancer), and found that while some inflammatory markers were linked with higher PSA levels, others were linked with lower PSA levels suggesting certain inflammatory markers may be linked with lower prostate cancer risk. Consistent with this, we studied men who all had prostate biopsies showing no cancer enrolled on a trial for a drug to prevent prostate cancer. Acute and chronic inflammation in the biopsy slides was present, respectively, in 15% and 77% of the negative biopsies. Presence of either was linked with a 35%-40% lower risk of prostate cancer on a study-mandated biopsy two years later. The challenge is that while many studies look at "inflammation," few dig deep and study the cell types that make up "inflammation" and when they do, results are interesting. For example, macrophages, a type of white blood cell, can be divided into M1 and M2. A study found M1 macrophages were more often present in early-stage prostate cancer, while M2 cells were more common in advanced disease, suggesting inflammation may promote or prevent prostate cancer, depending on the cell type analyzed. Intriguingly, there are data to suggest immune function is different in black and white men. First, black men have higher levels of a certain type of white blood cell (lymphocytes) but lower levels of other white blood cells (neutrophils). Second, in our study of negative prostate biopsies, black men had less inflammation in their prostates than white men. Third, when the tumor is examined, two studies both showed that prostate cancers in black men express higher levels of inflammatory-related genes compared to tumors in white men. Collectively, these studies suggest (1) inflammation may be linked with prostate cancer with some factors increasing risk and others lowering risk and (2) there are differences in inflammation between black and white men. This gives rise to our hypothesis that (1) various inflammatory components can be pro- or anti-prostate cancer and (2) black men have more pro- and less anti-prostate cancer inflammation, suggesting dysregulated inflammation in black men, which contributes to the greater risk of aggressive prostate cancer in black men. For the first time, we propose to perform an in-depth analysis of blood and tissue inflammatory markers and characterize the specific cell types present in the prostates of men with and without prostate cancer. All of this will be done using samples from 800 men who are either black or white men (400 of each race) to compare results between races. From this, we will be able to provide a detailed understanding of which inflammatory markers are linked with greater risk of prostate cancer particularly aggressive prostate cancer and which are linked with lower risk. We will also be able to assess whether black men had more pro-cancer inflammation and less anti-cancer inflammation relative to white men. Finally, as we have a lot of data on these men, we will be able to assess whether any differences by race are due to genetic factors (percent African-ancestry), dietar
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610750
Entities
People
- Stephen J. Freedland
Organizations
- Cedars-Sinai Medical Center
- United States Army