Prostate cancer is the most commonly occurring cancer in men of African descent in the US. Even though African American men have the highest prostate cancer rate in the world, there is relatively little information available about the etiologic factors that may explain these rates. Despite the knowledge that prostate cancer occurs at high rates in men of African descent in the Americas, very little data is available regarding the epidemiology of prostate cancer in native African men, even though prostate cancer seems to be prevalent in that population. The objective of the present study is to examine the role of genes that regulate the disposition of testosterone in prostate cancer etiology, and to evaluate whether these genes explain, in part, ethnic differences in prostate cancer rates. These genes include the cytochromes P450, CYP3A4 and CYP19, 5alpha-reductase II (SRD5A2), androgen receptor (AR), and the type II 3beta-hydroxy-steroid dehydrogenase (HSD3b2). All of these genes are involved in the downstream metabolism of testosterone, and thus focus our hypotheses on a relevant, defined set of metabolic pathways. The primary goals of this application are to 1) develop prostate cancer research infrastructure in Senegal, and 2) test feasibility of data collection for use in future studies of prostate cancer in West Africa.
Three specific aims are proposed here to focus these goals.
In Specific Aim 1, we will undertake multi-ethnic genotype to evaluate differences in the distribution of candidate genotypes in Senegales, US Caucasian, and African American controls.
In Specific Aim 2, we will develop a hospital-based prostate tumor registry at the Hopital General de Grand Yoff in Dakar, and describe the prostate cancer cases diagnosed at this hospital over a three-year period. Finally, in Specific Aim 3, we propose to evaluate whether there is a relationship between candidate genotypes and characteristics of prostate tumors in Senegalese men using a case-case study design, and compare these results with African American and US Caucasian men. In order to address these specific aims, we will identify a sample of incident prostate cancer cases and controls from Senegal, and make comparisons among these groups. 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. The information collected in Dakar will be compared against an ongoing study of prostate cancer in US Caucasian and African American men (""""""""Molecular Epidemiology of Prostate Cancer"""""""", funded by R01-CA85074, Timothy Rebbeck, Principal Investigator). The resources and data generated through this application will be used to establish additional studies of prostate cancer and potentially other cancers in Senegal including molecular epidemiological case-control studies of prostate cancer etiology. An understanding of the complex interplay of genetic variability at multiple loci and of environmental agents may improve our understanding of ethnic differences in prostate cancer etiology and risk prediction.
