The molecular genetics of prostate cancer.

The molecular genetics of prostate cancer, the second most common cause of cancer-related death in men, is poorly understood. Inherited factors are believed to account for 42% of the risk of prostate cancer, and although multiple chromosomal loci of susceptibility have been identified, the target genes for these loci have not been well defined. Its heterogeneous nature suggests that the predisposition to prostate cancer may involve multiple genes and variable phenotypic expression. Genes that have been found to play a role in progression of prostate cancer include GSTP1 and PTEN, as well as the androgen receptor (AR) gene. Evidence suggests that the AR signaling pathway can be activated by other ligands when androgen levels are low. Recent findings have also implicated Kruppel-like factor 6 (KFL6), E-cadherin, the p40 subunit of eukaryotic translation initiation factor (eIF3-p40), and Elongin C, but confirmatory evidence is required to clarify the roles of these factors. Technologic advances, such as complementary DNA and tissue microarrays, have facilitated identification of genetic alterations and investigations of their function, but improved tools for searching and analyzing genes are still needed.