The greater Baltimore area in Maryland has a large population of African-Americans and European-Americans, which makes this area most suitable to investigate differences in the exposure to prostate cancer risk factors among these two population groups. We designed a study that will use an integrated molecular epidemiology and translational research approach to examine causes for the excessive burden of prostate cancer among African-American men, including the study of tumor biological differences between African-American and European-American patients, supported by the collection of blood, urine, tissue samples, and survey data. Other epidemiological studies of prostate cancer have been established in recent years; however, only a few of these studies address the need for health disparity research and will have the opportunity to collect fresh-frozen tumor specimens from case subjects. Our study was implemented in two phases. The first phase, which started in April of 2005, constituted a pilot study to evaluate recruitment procedures. This phase was successful and the full study was initiated with minor changes to the protocol in April of 2006. The full study was completed in 2015 [976 cases (489 African-American and 487 European-American) and 1033 population-based controls (491 African-American and 542 European-American)]. We collected blood and urine from all individuals and paraffin-embedded and fresh-frozen tissue specimens form 135 prostatectomy surgeries. Cases are from two Baltimore hospitals, the Veterans Affairs Medical Center and the University of Maryland Medical Center. Cases have pathologically confirmed prostate cancer. The population-based controls were identified through the Maryland Department of Motor Vehicles database, and were frequency-matched by age and race to cases. The study involved the administration of a survey and collection of blood and urine from all study subjects. Fresh-frozen tumor specimens were obtained from cancer patients if they were available after prostatectomy. Our survey evaluates tobacco use, medication use, occupational history, diet, medical and sexual history, familial cancer history, and socioeconomic status. This case-control study was supported by an epidemiological infrastructure that has been developed for the NCI Maryland lung cancer case-control study. The lung cancer study is ongoing, and the controls that were recruited for the prostate cancer study are joint controls with the lung cancer study. Hence, population-based male controls had double eligibility for the concurrent lung and prostate cancer studies. To achieve an age and race matching of cases and controls in the prostate study, we will over-sample for male controls in the lung cancer study. The prostate cancer case-control study and the ongoing lung study at http://home.ccr.cancer.gov/GEMES/index.html. The website also describes the policy for collaborations involving data sharing. Our study is aimed at identifying differences in risk factor exposure and tumor biology between African-American and European-American men. We will test the hypothesis that environmental and genetic factors and their interactions contribute to the existing prostate cancer health disparity among African-Americans and European-Americans. Molecular work will be used to examine race/ethnic differences in tumor biology. Current activities in this study include the collection of additional data from pathology and medical records to have clinicopathology for all cases and information on disease recurrence as available. We are also obtaining survival data from the National Death Index. In collaboration with Rick Kittles at the University of Arizona, we typed 864 cases and all controls for ancestry marker to obtain proportions of West African, Caucasian, and Native American ancestry in these men. The analysis of survey data is in progress.