Genomic alterations in united states veterans with metastatic prostate cancer and self-reported agent orange exposure

You have accessJournal of UrologyCME1 Apr 2023PD21-09 GENOMIC ALTERATIONS IN UNITED STATES VETERANS WITH METASTATIC PROSTATE CANCER AND SELF-REPORTED AGENT ORANGE EXPOSURE JJ Zhang, Adam Weiner, Lorna Kwan, Sara Ahmed, Michael Kelley, Karim Chamie, Kara Maxwell, and Isla Garraway JJ ZhangJJ Zhang More articles by this author , Adam WeinerAdam Weiner More articles by this author , Lorna KwanLorna Kwan More articles by this author , Sara AhmedSara Ahmed More articles by this author , Michael KelleyMichael Kelley More articles by this author , Karim ChamieKarim Chamie More articles by this author , Kara MaxwellKara Maxwell More articles by this author , and Isla GarrawayIsla Garraway More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003287.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Agent Orange has been posited as an environmental risk factor for prostate cancer among United States Veterans. Prior studies have shown that Veterans with Agent Orange exposure are diagnosed at a younger age and at more advanced clinical stages. It is unknown if there are differences in somatic alterations among Veterans exposed to Agent Orange. METHODS: Genomic alterations were identified from clinical tumor testing conducted from 2019–2022 in a large cohort of Veterans with metastatic prostate cancer diagnosed from 2001–2022. Primary prostate and metastatic carcinoma tissue specimens were submitted for Foundation Medicine tumor-only sequencing. Baseline demographics, clinical, and genomic alterations data were stratified by Veteran self-reported exposure to Agent Orange in accordance with an Institutional Review Board approved protocol. RESULTS: Of the 2673 Veterans with metastatic prostate cancer who underwent tumor-only genomic testing, 629 reported exposure to Agent Orange (23.5%) and 2044 were not exposed. TMPRSS2-ERG fusions were more frequent in men who reported exposure to Agent Orange (35.1% vs 28.8%, p<0.01). Agent Orange exposure also correlated to higher rates of androgen receptor (AR) alterations (12.4% vs 9.5%, p=0.04) and FGFR1/2/3/4 alterations (3.3% vs 1.7%, p=0.01). On multivariable analysis, alterations in AR (OR 1.43, p=0.02), and FGFR1/2/3/4 (OR 1.84, p=0.03) remained more frequent in Veterans exposed to Agent Orange. As expected, age at prostate cancer diagnosis (OR 0.98, p<0.001) and Black/African-American race (OR 0.33, p<0.001) were associated with decreased odds of TMPRSS2-ERG alterations. In addition, current smoking status (OR 1.43, p=0.01) and rural environment (OR 1.33, p<0.01) were also associated with increased odds of a TMPRSS2-ERG fusion. There were no significant differences in alterations by Agent Orange exposure in TP53, CDK12, ERBB2, EGFR, BRCA, and genes implicated in the DNA damage response and repair (DDR), mismatch repair (MMR), and PTEN/PI3K/AKT pathways. CONCLUSIONS: Agent Orange exposure may contribute to tumor genomic alterations in AR and FGFR in prostate cancer. These findings hold potential prognostic and therapeutic implications for U.S. Veterans with metastatic prostate cancer. Source of Funding: NIH (K08CA215312, KNM; 5P50CA092131, R01 PAR-20-077, IPG); US DOD (W81XWH211075, IPG) Prostate Cancer Foundation (PCF17CHAL04, IPG; 20YOUNG02, KNM), Burroughs Wellcome Foundation (1017184, KNM); Basser Center for BRCA at UPENN (KNM); Jean Perkins Foundation (IPG), STOP Cancer Foundation (IPG) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e593 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information JJ Zhang More articles by this author Adam Weiner More articles by this author Lorna Kwan More articles by this author Sara Ahmed More articles by this author Michael Kelley More articles by this author Karim Chamie More articles by this author Kara Maxwell More articles by this author Isla Garraway More articles by this author Expand All Advertisement PDF downloadLoading ...