MP60-06 PROSTATE: INCORPORATING GENETIC ANCESTRY IN PROSTATE CANCER RISK SCORES FOR MEN OF AFRICAN DESCENT

Abstract

You have accessJournal of UrologyProstate Cancer: Markers (MP60)1 Sep 2021MP60-06 PROSTATE: INCORPORATING GENETIC ANCESTRY IN PROSTATE CANCER RISK SCORES FOR MEN OF AFRICAN DESCENT Joshua Linscott, Meghana Pagadala, Hannah Carter, Matthew Hayn, Moritz Hansen, Jesse Sammon, Karim Kader, and Stephen Ryan Joshua LinscottJoshua Linscott More articles by this author , Meghana PagadalaMeghana Pagadala More articles by this author , Hannah CarterHannah Carter More articles by this author , Matthew HaynMatthew Hayn More articles by this author , Moritz HansenMoritz Hansen More articles by this author , Jesse SammonJesse Sammon More articles by this author , Karim KaderKarim Kader More articles by this author , and Stephen RyanStephen Ryan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002095.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer (PrCa) is the most heritable of the solid organ malignancies. In addition, incidence and aggressive phenotypes are higher in African American men. Prior research into genetic heritability has focused on ancestry as defined by the patient. We explored ancestral genetic backgrounds with forensic genetic tools to define and develop a polygenic risk score (PRS) in African Americans. METHODS: Single nucleotide polymorphisms (SNPs) were imputed from a PrCa case-control study of >99,000 men (ELLIPSE) using the Michigan Imputation Server, 1000 Genomes Project, Eaglev2.3. Ancestral likelihood ratios were calculated by Forensic Research Reference on Genetics (FROG)-kb based on a previously described 55-SNP panel and define genetically separate African and European cohorts. GWAS was performed to identify PrCa risk SNPs and PRSice 2.3.1 to develop a PRS. An 80:20 split training:testing groups was used with AUC and ROC analysis. RESULTS: FROG-kb identified 4,507 and 5,334 individuals of African and European ancestry, respectively (Figure 1). In the African group, 6 SNPs reached significance, 1 on chromosome 1, 4 on chromosome 8, and 1 on chromosome 11. Four SNPs unique to African ancestry, were used to create a PRS. Individually, family history (FH), age, and PRS achieved AUCs of 0.56, 0.54, and 0.60 respectively. Combined PRS, FH, and Age improved AUC to 0.64 (Figure 2). CONCLUSIONS: A 55-SNP panel identified genetic ancestral groups for GWAS analysis, which defined 4 PrCa associated SNPs specific to African genetic inheritance. The resulting PRS predicted PrCa better than FH and Age in African American men. A combined model performs similar to previously published studies in European cohorts. Here we have achieved comparable AUC using only 4 SNPs, in a group at higher risk for aggressive PrCa. Source of Funding: none © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1043-e1043 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joshua Linscott More articles by this author Meghana Pagadala More articles by this author Hannah Carter More articles by this author Matthew Hayn More articles by this author Moritz Hansen More articles by this author Jesse Sammon More articles by this author Karim Kader More articles by this author Stephen Ryan More articles by this author Expand All Advertisement Loading ...