Self-Identified African Americans and prostate cancer risk: West African genetic ancestry is associated with prostate cancer diagnosis and with higher Gleason sum on biopsy.

Concerns about overtreatment of clinically indolent prostate cancer (PrCa) have led to recommendations that men who are diagnosed with low-risk PrCa be managed by active surveillance (AS) rather than immediate definitive treatment. However the risk of underestimating the aggressiveness of a patient's PrCa can be a significant source of anxiety and a barrier to patient acceptance of AS. The uncertainty is particularly keen for African American (AA) men who are about 1.7 times more likely to be diagnosed with PrCa than European American (EA) men and about 2.4 times more likely to die of this disease. The AA population, as many other populations in the Americas, is genetically heterogeneous with varying degrees of admixture from West Africans (WAs), Europeans, and Native Americans (NAs). Recommendations for PrCa screening and management rarely consider potential differences in risk within the AA population. We compared WA genetic ancestry in AA men undergoing standard prostate biopsy who were diagnosed with no cancer, low-grade PrCa (Gleason Sum 6), or higher grade PrCa (Gleason Sum 7-10). We found that WA genetic ancestry was significantly higher in men who were diagnosed with PrCa on biopsy, compared to men who were cancer-negative, and highest in men who were diagnosed with higher grade PrCa (Gleason Sum 7-10). Incorporating WA ancestry into the guidelines for making decisions about when to obtain a biopsy and whether to choose AS may allow AA men to personalize their approach to PrCa screening and management.

Epigenetic risk score improves prostate cancer risk assessment.

BACKGROUND: Early detection of aggressive prostate cancer (PCa) remains crucial for effective treatment of patients. However, PCa screening remains controversial due to a high rate of overdiagnosis and overtreatment. To better reconcile both objectives, more effective methods for assessing disease severity at the time of diagnosis are needed. METHODS: The relationship between DNA-methylation and high-grade PCa was examined in a cohort of 102 prospectively enrolled men who received standard 12-core prostate biopsies. EpiScore, an algorithm that quantifies the relative DNA methylation intensities of GSTP1, RASSF1, and APC in prostate biopsy tissue, was evaluated as a method to compensate for biopsy under-sampling and improve risk stratification at the time of diagnosis. RESULTS: DNA-methylation intensities of GSTP1, RASSF1, and APC were higher in biopsy cores from men diagnosed with GS ≥ 7 cancer compared to men with diagnosed GS 6 disease. This was confirmed by EpiScore, which was significantly higher for subjects with high-grade biopsies and higher NCCN risk categories (both P < 0.001). In patients diagnosed with GS ≥ 7, increased levels of DNA-methylation were present, not only in the high-grade biopsy cores, but also in other cores with no or low-grade disease (P < 0.001). By combining EpiScore with traditional clinical risk factors into a logistic regression model, the prediction of high GS reached an AUC of 0.82 (95%CI: 0.73-0.91) with EpiScore, DRE, and atypical histological findings as most important contributors. CONCLUSIONS: In men diagnosed with PCa, DNA-methylation profiling can detect under-sampled high-risk PCa in prostate biopsy specimens through a field effect. Predictive accuracy increased when EpiScore was combined with other clinical risk factors. These results suggest that EpiScore could aid in the detection of occult high-grade disease at the time of diagnosis, thereby improving the selection of candidates for Active Surveillance.