A large-scale genetic association study of prostate cancer in a multi-ethnic population

Prostate cancer is a serious public health problem in the United States and abroad. Despite decades of research, the etiology remains elusive, however several characteristics of the disease are well known. There is distinct racial/ethnic variation in risk of prostate cancer, risk increases with age, androgen ablation therapy is an effective treatment for advanced prostate cancer, and rats develop prostate cancer after administration of testosterone.; Given the apparent role of androgens and the interesting racial/ethnic variation in risk, the role of single nucleotide polymorphisms (SNPs) in genes involved in androgen metabolism in the prostate was studied in relation to prostate cancer risk in African-American, Japanese-American, Latino, and White men. The three genes studied in this dissertation were SRD5A2, HSD3B1, and AR.; There was an apparent increased risk of advanced prostate cancer associated with the T allele of the A49T SNP in the SRD5A2 gene in African-American and Latino men, but not in Japanese-American and White men. There was no association between the V89L SNP in the SRD5A2 gene and risk of prostate cancer in any of the four ethnic groups studied.; There was an increased risk of advanced prostate cancer associated with the LL genotype of the F286L SNP of HSD3B1 in African-American men. The LL genotype was not present at an appreciable frequency in the other racial/ethnic groups.; A total of eleven SNPs in the AR gene were studied using both a single SNP analysis and a haplotype analysis. Although there did not appear to be a strong association with prostate cancer risk, the haplotype diversity was interesting. Although a total 2,048 haplotypes were possible (211), only nineteen were observed, and only ten at a frequency of one percent or greater. The Japanese-American group had only one haplotype whereas the African-Americans showed the greatest diversity.; Several candidate SNPs in genes involved in androgen metabolism in the prostate have been identified as potentially associated with prostate cancer risk in the multi-ethnic population studied. Additional studies are recommended to confirm these findings.