Socio-demographic, clinical, and genetic predictors of low versus high Gleason score among men with prostate cancer in the Detroit Research on Cancer Survivorship (ROCS) cohort.

5092 Background: Black men with prostate cancer typically present with a higher Gleason Score (GS) and more aggressive disease than White men. The purpose of this project is to describe the relationship between socio-demographic, clinical and genomic variability with GS categories among 599 men with prostate cancer in the Detroit Research on Cancer Survivorship (ROCS) cohort. Methods: Detroit ROCS is a cohort of Black cancer survivors based in the Detroit Metropolitan area. Patient data was obtained from a self-administered questionnaire, cancer registry and biologic samples were collected through at home phlebotomy or mailed saliva kits. The primary analysis focused on clinical and genetic differences between men with GS ≤ 6 vs. ≥ 7. Germline data was compiled into the multi-ethnic genotyping array (MEGA) data panel and 21 genes were chosen for analysis (2,393 SNPS) based on their clinical applicability. Eight tools were used in ANNOtate VARiation (ANNOVAR) to determine whether a genetic variant was pathogenic. The determination of pathogenicity was defined by at least seven of the tools indicating variant pathogenicity. We assessed the rate of pathogenic variants for each GS category. Multivariable models of predictors of GS categories were conducted using logistic regression. Results: The categories across GS in the ROCS cohort included: ≤ 6 (21.2%), 3+4 (40.4%), 4+3 (20.2%) and ≥ 8 (18.2%). Variables associated with increased GS (≥ 7 vs. ≤ 6) included age (for each 10-year increase the OR was 1.71, 95% CI 1.26-2.34) and body mass index (for each 5 unit increase the OR was 1.27, 95% 1.06-1.54). Higher vs. lower education (some college education or higher vs less than or equal to a high school education) was associated with lower GS, OR 0.58, 95% CI 0.37-0.96. Out of a total of 2,393 SNPs analyzed, 880 (36.8%) were polymorphic, of which 684 had a minor allele frequency (MAF) >0.001, and 282 had a MAF >0.05. Overall, 16.2% of the men were carriers of a pathogenic variant, the most common of which were ATR (9.3%), FANCL (3.5%), and ATM (1.7). Men with GS 6 had a lower rate of pathogenic variants (8.7%), than those with GS 3+4 (18.2%), GS 4+3 (16.5%), and GS 8 (20.2%). Men with a pathogenic variant in ATR were 2.87 (95% CI 1.08- 7.65) times more likely to have GS ≥ 7 vs. ≤ 6. Higher GS was specifically associated with SNP rs33972295 in the ATR gene. Conclusions: The relationship between older age, higher BMI, and less educational background suggests that sociodemographic risk factors should be accounted for when assessing risk for higher grade prostate cancer. Identification of genomic differences associated with aggressive prostate cancer may provide insight into new targeted therapy options.