This project is designed to compare the molecular genetics of prostate cancer development in two ethnic groups which show large differences in incidence and mortality. It is clear that African-American men are disproportionately affected by prostate cancer relative to Caucasian- American men. The reasons for the increased incidence and mortality of blacks have not been delineated, and the hypothesis to be tested in this project is that different genetic lesions occur in prostate tissue in blacks relative to white men. In order to test this hypothesis, we intend to screen DNA extracted from early lesions in both races and to compare the frequency, size, and location of alterations in the genome of these two populations. To perform a screen of a large number of molecular genetic sites we will use Comparative Genomic Hybridization (CGH), a technique developed in our Division of Molecular Cytometry, to map the sequence copy number of tumor DNA relative to normal, benign tissue DNA. This copy number map should delineate all regions in the prostate cancer tissue DNA where an abnormal number of copies are present. Recurrent loss of a region generally indicates the location of a tumor suppressor gene while recurrent amplification indicates the location of an activated oncogene. A comparative map of this nature will be generated for similar, early tumor stages and grades in the two races, so as to determine whether there exist unique prostate cancer induction sites within the genome of African-American. This same analytical procedure will be applied to benign tissue DNA from these same donors so as to analyze for significant copy number alterations that may be present prior to neoplasia. Epidemiological determination of possible inducing conditions in the donors of distinction also will be performed. Thus, smoking status, socio-economic factors, and history of medical care will be gathered and compared between the individuals who show any unique molecular genetic indicators. Identification of correlations between genetic and environmental effects with particular molecular genetic changes in blacks relative to whites may lead to clarification of the reasons for a large incidence and mortality difference between these two races.
| Kim, S H; Godfrey, T; Jensen, R H (1999) Whole genome amplification and molecular genetic analysis of DNA from paraffin-embedded prostate adenocarcinoma tumor tissue. J Urol 162:1512-8 |
