Biomarker Predicts Aggressive Prostate Cancer in African American Men

Researchers have identified a subset of six biomarkers that together may predict the risk of more aggressive prostate cancer among African American men. The results may partly explain the biological basis for the differences in outcomes between African American and European American prostate cancer patients.

The study is the largest prostate cancer predictive biomarker analysis in African American men to date, according to the study authors led by Kosj Yamoah, MD, PhD, a resident at Thomas Jefferson University Hospital in Philadelphia. The study results were published in the Journal of Clinical Oncology.

African American men have a greater incidence of prostate cancer and greater mortality compared with their European descent counterparts in the United States. Both genetic susceptibility and differences in socioeconomics have been linked to these disparities.

Because differences in the aggressiveness of disease at diagnosis have been noted between the two, Yamoah, along with Edward M. Schaeffer, MD, PhD, director of the prostate cancer program at the James Buchanan Brady Urological Institute at Johns Hopkins School of Medicine, and colleagues, reasoned that there may be a biological difference in prostate cancer development between the two groups.

If validated in future studies, the six biomarkers identified could be used to predict the risk of ethnicity-dependent clinical outcomes. According to the study authors, the biomarkers may also partly explain why African Americans are more likely to have faster-progressing prostate cancer that can lead to decreased survival.

Through a comprehensive literature search, the researchers identified 20 biomarkers that have been linked to tumor aggressiveness or pathogenesis. Then, using a retrospective matched cohort, they assessed the expression levels of these 20 genes in tumor biopsy samples. Patients who underwent a radical prostatectomy and lymph node dissection at four institutions between 1987 and 2012 were included-154 African American patients and 243 European American patients.

Six of these genes showed a statistically significant difference in expression between the two groups-ERG (P < .001), AMACR (P < .001), SPINK1 (P = .001), NKX3-1 (P = .03), GOLM1 (P = .03), and androgen receptor (P = .04).

Moreover, dysfunction or loss-of-function mutations in each of these genes-AMACR (P = .036), ERG (P = .036), FOXP1 (P = .041), GSTP1 (P = .049), NKX3-1 (P = .025), and RB1 (P = .037)-predicted risk of pathologic T3 disease that was specific to ethnicity.

“These data suggest that prostate cancer may arise from different tumor progenitors and/or distinct molecular pathways in European American men compared with African American men,” wrote the authors in their discussion.

Of four prognostic biomarker signatures, including three commercially available ones used in clinical practice, none exhibited ethnicity-specific predictive value.

“The ability to identify a subset of African American men who harbor aggressive disease will enable clinicians to more accurately risk stratify these patients for appropriate treatment recommendations that improve disease control and ultimately reduce the disparities in outcomes in this patient population,” concluded the study authors.