PD11-12 IDENTIFICATION OF GENES ASSOCIATED WITH THE RISK OF REQUIRING BPH SURGERY

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology (PD11)1 Sep 2021PD11-12 IDENTIFICATION OF GENES ASSOCIATED WITH THE RISK OF REQUIRING BPH SURGERY Samuel Antoine, Alan Makedon, and Granville Lloyd Samuel AntoineSamuel Antoine More articles by this author , Alan MakedonAlan Makedon More articles by this author , and Granville LloydGranville Lloyd More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001986.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) have high prevalence and increasingly large societal burden. The pathogenesis of BPH remains unclear but heritable factors have been shown to significantly influence prostate volume and increase the chances of requiring surgery. This study aimed to assess the presence of genomic differences in men that require BPH surgery when compared to men that do not. METHODS: We evaluated single-nucleotide polymorphism (SNP) based heritability of BPH and conducted a genome-wide association study (GWAS) of BPH surgery risk using cases and controls. Scrubbed data was obtained from the University of Colorado Biobank and exempt from IRB approval. Using SAIGE v0.39, 103,154 LD-pruned SNPs of MAF ≥0.01 across 33,864 samples were used to generate kinship estimations with relatedness cutoff of 0.0625. Significance of p=10-5 was used to identify relevant SNPs. These then were used to identify associated genes using SeattleSeq (University of Washington). RESULTS: 33,864 total patients were considered, and after selection for male gender and age 50 or greater, patients with any diagnosis of prostate or bladder cancer were excluded. Patients with only one visit were excluded. Patients were screened for presence or absence of BPH surgical or minimally invasive procedure, and men who had required a procedure (transurethral resection or laser vaporization; simple prostatectomy) were compared to men that did not. No thermal ablation or prostatic lift patients were present in this sample. 149 cases and 6,204 controls were analyzed. GWAS analysis revealed 131 SNPs (on/near 25 genes, p ≤10-5) that predicted need for BPH treatment. Genes associated with a p ≤10-6 include DOCK4, a cytokinesis gene; MRAP, a melanocortin receptor-interacting protein; and NCOA3, a hormone receptor coactivator (Table 1). CONCLUSIONS: We have identified genes significantly associated with severe LUTS/BPH requiring surgical treatment. These findings suggest a significant heritable component of LUTS/BPH. These genes may provide targets for future research, treatments or development of a polygenic risk score to identify those at risk for progression to medical/surgical treatment. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e202-e202 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Samuel Antoine More articles by this author Alan Makedon More articles by this author Granville Lloyd More articles by this author Expand All Advertisement Loading ...