Pd56-01 Comparative Genomic Analysis of 1,043 African American and Non-african American Prostate Cancers: a Report From the Decipher Grid Collaborative
Year: 2018
Type: article
Study design: Observational Study
Abstract: INTRODUCTION AND OBJECTIVES: Racial disparities in prostate cancer incidence and mortality are well known.Here we present initial results from the largest study of race and prostate cancer genomics.METHODS: We obtained de-identified genome-wide expression profiles from clinical use of the Decipher RP test in 9,953 men from the GRID registry database.Physician reported patient race was annotated according to US Census Bureau categories as one of Black/African-American, White (non-Hispanic), White (Hispanic), Asian or Other (American Indian, Native Alaskan or Hawaiian/Pacific Islander).Multivariable logistic regression odds ratio (OR) analysis was used to assess the association of 82 GRID signatures with African-American (AAM) as compared to non-African American (non-AAM) race status.RESULTS: A subset of 1,043 men had known race status in the GRID including 529 African American (51%), 23 Asian (2%), 14 White (Hispanic) (1%), 472 White (Non-Hispanic) (45%) and 5 Other.The median age at surgery was 63 years (range, 41-81 years).AAM tended to be younger (p<0.004), had higher median preoperative PSA (p<0.001),lower Grade Group disease (p¼0.04),higher rates of positive margins (p<0.001) and bladder neck invasion (p¼0.01) as compared to non-AAM men.Decipher risk categories were not significantly different between the groups (p¼0.6).Non-AAM men had more ERG (40% vs 23%, p<0.001) and ETS (10% vs 6%, p¼0.02) expression, whereas AAM had more Triple Negative (48% vs 39%, p<0.005) and SPINK1 (23% vs 11%, p<0.001) molecular subtype tumors.After adjusting for clinical and pathological risk features in multivariable analysis, AAM were less likely to be PAM50 Luminal (A or B, OR: 0.58, p¼0.01), more Basal-like (OR: 2.1, p<0.001), had lower Androgen Receptor activity (OR: 2.1, p¼0.01) and high POR-TOS radiation response (OR: 2.2, p¼0.01).AAM cancers were associated with higher levels of cancer pathway genes sets such as immune response (TNFA signaling via NFKB, interferon alpha, gamma response), apoptosis, hypoxia, reactive oxygen species, K-Ras and p53 signaling, whereas non-AAM tumors were associated with higher levels of fatty acid metabolism, glycolysis, Myc targets, mitotic spindle, DNA repair, PI3K via AKT/mTOR and WNT via beta catenin signaling.CONCLUSIONS: Significant biological differences in prostate cancer appear to be dependent in part upon a man 0 s racial ancestry.Here we demonstrate the value of genomic data collected in the GRID database from clinical use of the Decipher test and from collaboration among its users.Additional ancestry and race data should be collected from African American as well as other racial groups to further study its impact on heterogeneity of prostate cancer and potential implications for treatment in the future.
Source: The Journal of Urology
Authors: Walter Rayford, Jordan Alger, Mandeep Takhar, Jennifer Jordan, Kamlesh Yadav, Mohammed Alshalalfa, Darlene Dai, Nick Fishbane, Takara Scott, Jill Collins, Britney Bender, Mohsen Ahmed, Jonathan Lehrer, Nicholas Erho, Elai Davicioni, Mark D. Greenberger, Randy Bradley, Wei Phin Tan, Justin Watson, Mathew Beamer, Lambros Stamatakis, Darrell J Carmen, Kosj Yamoah, Jonathan Hwang, Leslie A. Deane, Ashutosh Tewari
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2795784261