Racial differences in the androgen/androgen receptor pathway in prostate cancer

Pathologic and epidemiologic data suggest that while little racial variation exists in prostate cancer prevalence ("autopsy cancer"), striking racial variation exists for the clinically diagnosed form of the disease. A review of the available literature was performed to define whether racial differences in serum androgen levels or qualitative or quantitative differences in the androgen receptor were correlated with prostate cancer incidence or severity. Black men were found to be exposed to higher circulating testosterone levels from birth to about age 35 years. Such differences were not consistently noted among older men. Significant differences also were found for dihydrotestosterone metabolites among black, white, and Asian men. Unique racial genetic polymorphisms were noted for the gene for 5α-reductase type 2 among black and Asian men. Novel androgen receptor mutations recently have been described among Japanese, but not white, men with latent prostate cancer. Finally, androgen receptor gene polymorphisms leading to shorter or longer glutamine and glycine residues in the receptor protein are correlated with racial variation in the incidence and severity of prostate cancer. This same polymorphism also could explain racial variation in serum prostate-specific antigen levels. Collectively, these data strongly suggest racial differences within the androgen/androgen receptor pathway not only exist but could be one cause of clinically observed differences in the biology of prostate cancer among racial groups.