Prostate cancer susceptibility genes: many studies, many results, no answers

Since the first report of a genome-wide scan for hereditary prostate cancer (HPCA hereinafter) in 1996, several publications have presented data implicating various chromosomal regions by linkage analysis without any consequential identifications of the target genes. The most intensive attention has been focused on chromosome 1, and it has been proposed to contain at least three sub-chromosomal regions (HPC1, PCAP, CAPB) harboring putative prostate cancer susceptibility genes. Nevertheless, one susceptibility gene, ELAC2/HPC2 at chromosome 17, has now been identified. Yet it seems to have a questionable role in prostate cancer predisposition. HPCA susceptibility loci have become undeniable archenemies of prostate cancer investigators, as the results of candidate gene analyses have been bewilderingly inconclusive. Predisposition to prostate cancer is most likely to be caused by several genes, different models of Mendelian inheritance, incomplete penetrance and varying population ethnicity frequencies. We will review the current state of the HPCA field and discuss the difficulties associated with identifying prostate cancer susceptibility genes.