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Prostate cancer is the most commonly occurring cancer in U.S. men. African American men have the highest prostate cancer incidence in the world, and significantly higher prostate cancer mortality than U.S. Caucasians. There is relatively little information available about the factors that may explain the disparity in outcomes related to prostate cancer across ethnicity. The objective of the present study is to examine the role of genes and screening behaviors in explaining differences in prostate cancer outcomes African Americans and U.S. Caucasians. These candidate genes include those that regulate androgen metabolism (and thus may affect growth and differentiation of prostate tumors) as well as immunomodulatory genes (that may affect the body's response to the present of a tumor).

In Specific Aim 1, we will systematically evaluate the relationship of candidate genes with characteristics of prostate tumors at the time of diagnosis (e.g., histopathological characteristics and prostate specific antigen levels), and compare these relationships between African American and Caucasian men. In Specific Aim 2, we propose to follow men who have undergone prostatectomy for treatment of their prostate cancer to determine whether genotypes and other factors predict biochemical relapse-free survival, and again compare these relationships between African American and Caucasian men. In Specific Aim 3, we propose to extend the analyses in Specific Aims 1 and 2 to consider the interaction of these predictors with prostate cancer screening practices to determine whether biological factors interact with behavioral (screening) factors to influence prostate cancer outcomes, and to compare these relationships between African American and Caucasian men.

In order to address these hypotheses, we will undertake a study using an existing subject accrual system to identify a sample of 1000 incident prostate cancer cases who have undergone prostatectomy for the treatment of their cancer. Half of these will be African American and half will be Caucasian. Risk factor information will be obtained from a questionnaire interview, a biosample containing DNA will be collected using a non-invasive cheek swab method, and pathology information will be collected using a standardized medical record abstraction approach. Systematic follow-up of these men will be undertaken to ascertain their clinical status. We hypothesize that an understanding of the complex interplay of screening behaviors and genetic variability may identify the caseu of disparities in prostate cancer outcomes by ethnicity, and be used to more effectively apply prostate cancer prevention and control strategies.

Key personnel

Name Organization Role on the project

Timothy R. Rebbeck, Ph.D. University of Pennsylvania Prinicipal Investigator

S. Bruce Malkowicz, M.D. University of Pennsylvania Co-investigator

Anne-Marie Martin, Ph.D. Pennsylvania Hospital Co-investigator