Cladistic Association Analysis of Genetic Effects on Prostate Cancer in African Americans

摘要

The goals of this project are to (1) provide a formal evaluation of variation at three candidate gene regions for prostate cancer (the androgen receptor gene, 5alpha-reductase type 2 gene, and the chromosome X region Xq27- 28) in 2,000 clinically evaluated unrelated men, and (2) exploit the evolutionary history of haplotypes in order to determine if haplotypic differences account for phenotypic variation in prostate cancer, prostate specific antigen (PSA) levels and disease progression. To date we have collected blood and clinical data from about 1700 unrelated men with and without prostate cancer. Molecular genotyping of three polymorphisms within the androgen receptor has been performed in 1700 individuals and three polymorphism within the 5alpha- reductase type 2 gene in about 1100 of the subjects. In addition, five microsatellites have been typed within the candidate gene region in and around Xq27-28 for all subjects. Preliminary analyses reveal significant linkage disequilibrium between the androgen receptor markers in African Americans and suggest a strong correlation between specific androgen receptor haplotypes and prostate cancer. The other two gene regions have yet to be analysed for association with prostate cancer.