Germline alterations among Hispanic men with prostate cancer

10534 Background: With the growing indications for germline testing in prostate cancer (PCa), there is accumulating evidence that African American and Hispanic men with PCa are significantly under-tested compared to non-Hispanic white (NHW) men. Given this, little is known about the pathogenic germline variant landscape in Hispanic men with PCa. Methods: This was a retrospective cohort analysis of 17,256 men with PCa who underwent diagnostic germline testing through a commercial laboratory (Invitae) from 2015-2020. Self-identified Hispanic and NHW men were selected for comparative analysis. The primary endpoint was the rate of pathogenic/likely pathogenic (PLP) germline alterations in Hispanic men among 25 genes associated with PCa. Secondary endpoints included comparison of PLP rates in Hispanic vs NHW men, the rate of specific PLP alterations, and the rate of variants of uncertain significance (VUS). Fisher’s exact test was used to compare germline alteration rates for significance. Results: We identified 508 Hispanic and 12,542 NHW men with PCa who underwent testing during the study period. Median age at the time of testing was 69 vs 67 years in Hispanic vs NHW cohorts. A family history of PCa was reported in 21.1% (N=108) vs 27.3% (N=3428) in the Hispanic vs NHW cohorts, respectively (p=0.002). The PLP alteration rate was 7.1% in the Hispanic cohort and this rate was numerically lower but not significantly different when compared to the NHW cohort (9.7%) (p=0.058). A significantly higher rate of VUS was seen in the Hispanic cohort (Table). The four most frequently detected genes with PLP alterations in both cohorts were ATM, BRCA1, BRCA2, and CHEK2. Only the rate of CHEK2 alterations was significantly different between cohorts among all 25 genes analyzed (Table). Conclusions: In this analysis, the PLP alteration rate among Hispanic men was 7.1%, a much higher rate than has been previously reported, and the germline genomic landscape was similar to that of NHW men. The VUS rate was significantly higher among Hispanic men, a known consequence of under-testing among minority populations.These data support germline testing in Hispanic men with prostate cancer and emphasize the importance of improving testing rates.[Table: see text]