Molecular Mechanisms Underlying Prostate Cancer Disparities (GENCADE)

Molecular Mechanisms Underlying Prostate Cancer Disparities.

The purpose of this study is to further elucidate the molecular mechanisms underlying prostate cancer disparities. In previous work the investigators have identified a set of differentially deregulated genes in African American versus Caucasian American prostate cancer. Based on these findings, they hypothesize that they will be able to validate these targets, originally identified in the previous work conducted at The George Washington University Medical Center, in an independent Duke University Medical Center cohort of prostate cancer specimens. In addition, the investigators hypothesize that they will be able to discover novel targets in the Duke University Medical Center cohort of prostate cancer specimens because of regional differences.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Device: Biopsy or prostatectomy

Detailed Description

Individual patient African American and Caucasian American prostate biopsy cores or surgical specimens will be obtained from the following procedures: transrectal ultrasound biopsy of the prostate (TRUSBxP), MR fusion biopsy, intra-operatively (IO) at the time of prostatectomy. Using cellular DNA and RNA, isolated from prostate cancer and patient-matched normal prostate biopsy cores or surgical specimens, the investigators will perform ancestral genotyping, exon arrays, targeted RNA sequencing, and epigenetic analyses. As controls, blood will also be collected. Genomic data from blood and tumor tissue will be compared.

• Study Type: Observational
• Enrollment (Actual): 226

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

The study population includes African American and Caucasian American patients (self-reported) undergoing clinically indicated diagnostic biopsies for a suspected prostate malignancy or intra-operative biopsies of patients undergoing clinically indicated prostatectomy for a confirmed prostate cancer.

Description

Inclusion Criteria:

• Suspected malignancy of prostate cancer
• Self-reported race of African American or Caucasian American
• Age >/= 18 years
• Able to read, understand and sign an informed consent document

Exclusion Criteria:

• Collected tumor tissue is inadequate for DNA and RNA analysis and/or is not positive for adenocarcinoma of the prostate.
• Patients with prior systemic therapy will not be eligible for the study, i.e. radiation or chemo or immunotherapy.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Caucasian; Caucasian subjects having a biopsy or prostatectomy.	Device: Biopsy or prostatectomy
African American; African American subjects having a biopsy or prostatectomy.	Device: Biopsy or prostatectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of high and low expression of identified gene targets in Caucasian and African American specimens	Total RNA will be interrogated for mRNA expression patterns with the Affymetrix Human Exon 1.0 ST GeneChip. Microarray data will be normalized by quantile normalization with background correction. Targeted RNA sequencing of the previously identified genetic factors specific to African American prostate cancer will confirm altered expression and alternative splicing in these deregulated genes. The Agilent Technologies SureSelect RNA Custom Capture Kit will capture and sequence transcripts. Epigenetic analyses of the genetic factors specific to African American prostate cancer will identify DNA methylation and histone modification patterns in these deregulated genes. The Sequenom EpiTYPER will screen for differential methylation and methylation differences will be quantified using pyrosequencing. Differential histone modification patterns will be explored. Analysis will be performed on 33 prostate cancer biopsy specimens from each of 6 groups stratified by race and Gleason grade.	up to 2 years

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Steven Patierno, PhD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2014
• Primary Completion (Actual): October 14, 2019
• Study Completion (Actual): October 14, 2019

Study Registration Dates

• First Submitted: June 12, 2014
• First Submitted That Met QC Criteria: August 29, 2014
• First Posted (Estimate): September 1, 2014

Study Record Updates

• Last Update Posted (Actual): November 13, 2020
• Last Update Submitted That Met QC Criteria: November 11, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: prostate cancer; prostate biopsy; prostatectomy
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: Pro00053535

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No