Biomarkers predict aggressive prostate cancer in African Americans

African American men may develop a more aggressive type of prostate cancer that is distinctly different on a genomic level from prostate cancer in American men of European descent. African American men are also twice as likely to die from it.

Because of this disparity, researchers at four North American medical centers assessed various biomarkers to evaluate whether (and which) genetic and biologic factors affect the pathogenesis and progression of prostate cancer. Their findings are published in the Journal of Clinical Oncology.

“This study, this line of research, is about finding better and more appropriate therapies for African American men,” says the corresponding author of the study, Kosj Yamoah, MD, PhD, chief resident in the Department of Radiation Oncology at the Sidney Kimmel Cancer Center at Thomas Jefferson University in Philadelphia, PA. “The first step is to figure out how prostate cancer is different and more aggressive at the genomic level.”

To do so, the researchers reviewed the literature to find 20 validated biomarkers that are functionally associated with prostate cancer initiation and progression. These included prostate cancer markers and genes involved in hormone receptor function and cell metabolism. They then examined the clinical records of 154 African American and 243 European American prostate cancer patients from four medical centers. The researchers matched the disease characteristics of these patients using the Cancer of the Prostate Risk Assessment postsurgical score (CAPRA-S), which predicts disease severity and risk of recurrence after surgical removal of the prostate. They analyzed these data to look for interaction between ethnicity and the 20 biomarkers in order to predict clinicopathologic outcomes.

Of the biomarkers they examined, 6 of them (ERG, AMACR, SPINK1, NKX3-1, GOLM1, and androgen receptor) showed statistically significant differential expression in African American men compared with European American men. Some of the biomarkers (AMACR, ERG, FOXP1, GSTP1, NKX3-1, and RB1) predicted risk of pathologic T3 disease in an ethnicity-dependent manner. Other biomarkers (GOLM1, SRD5A2, and MKi67) predicted clinical outcomes, including 3-year biochemical recurrence and metastasis at 5 years.

Most significantly, the researchers found that a greater proportion of African American men than European American men (51% vs 35%) had a subtype described as triple-negative disease, which is characterized by little or no ERG, ETS, and SPINK1 biomarkers.

“Much of what we understand in terms of the genetics of prostate cancer to date has been based on clinical trials in Caucasian men,” Dr. Yamoah said. “However, the data here suggest that a subset of African American men may have a type of prostate cancer that arises from molecular pathways that are distinctly different from those of European American men.”

The next steps are to “refine the biomarkers that will capture these differences and develop approaches that help reduce the disparities in outcomes that we see,” said Dr. Yamoah. “This, and our previous work in this area, shows that some African American men with prostate cancer might have a better shot at survival if they are treated with a different approach than standard of care.”