Presentation Authors: Sandra Gaston*, Boston, MA, Rick Kittles, Duarte, CA, Soroush Rais-Bahrami, Peter Kolettis, James Bryant, Jeffrey Nix, Birmingham, AL, Mark DeGuenther, George Adams, Homewood, AL, Ebony Shah, Indianapolis, IN, James Kearns, Ravi Chinsky, Kerry Dehimer, Norma Terrin, Hong Chang, Boston, MA, William Grizzle, Birmingham, AL
Introduction: Concerns about overtreatment of clinically indolent prostate cancer (PrCa) have led to recommendations for less screening, fewer biopsies, and the management of low-risk PrCa by active surveillance rather than immediate definitive treatment. However the risk of missing or failing to treat an aggressive prostate PrCa can be a significant source of anxiety. The uncertainty is particularly keen for African American (AA) men who are about 1.7 times more likely to be diagnosed with PrCa and about 2.4 times more likely to die of this disease. Many studies show that genetic factors play a role in the increased risk of PrCa in AA. The AA population, as many other populations in the Americas, is genetically heterogeneous with varying degrees of admixture from West Africans, Europeans and Native Americans. Recommendations for PrCa screening and management rarely consider potential differences in risk within the AA population.
Methods: 96 consecutive eligible self-identified AA men were prospectively enrolled in this study. We compared West African (WA) genetic ancestry in the men who were diagnosed with no cancer, low grade PrCa (Gleason Sum 6) or higher grade PrCa (GS 7-10) on a stand-of-care systematic prostate biopsy. Each man's WA, European and Native American ancestry was estimated by DNA testing using a panel of 105 ancestry informative markers (single nucleotide polymorphisms).
Results: We found that WA genetic ancestry was significantly higher in AA men who were diagnosed with PrCa on biopsy, compared to AA men who were cancer negative, and was highest in AA men who were diagnosed with higher grade PrCa (GS 7-10). We evaluated % WA ancestry as a predictor of GS 7-10 cancer both as a single variable and in combination with other variables used clinically to make decisions about whether a patient should undergo prostate biopsy. For prediction of any cancer on biopsy, addition of WA genetic ancestry to a base model that includes age, PSA and prostate volume increases the model R square by 75% with P = 0.0245. For predicting GS 7-10 cancer, addition of WA ancestry to the base model improves R square by 72% with P = 0.0238. Thus when considered in combination with age, PSA and prostate size, % WA ancestry remained a strong predictor of both PrCa diagnosis and GS 7-10 cancer on biopsy.
Conclusions: Incorporating West African ancestry into the guidelines for making decisions about when to obtain a biopsy and whether to choose active surveillance may allow AA men to personalize their approach to prostate cancer screening and management.
Source of Funding: Department of Defense Prostate Cancer Research Program: W8XWH-10-1-0543 (William E. Grizzle, PI) and W81XWH-10-1-0544 (Sandra M. Gaston, PI)