Collection of Prostate Cancer Families and Mapping Additional Hereditary Prostate Cancer Genes (HPC2, HPC3,...)

Abstract

Abstract : Segregation analyses of familial prostate cancer have provided evidence for the existence of dominantly-acting prostate cancer susceptibility alleles, with such genes being estimated to be responsible for about nine percent of all cases of prostate cancer in the U.S. These findings provided the basis for our genome wide scan for linkage in hereditary prostate cancer (HPC) families, leading to the identification of the HPC1 locus at 1q24-25 as the first reported linkage in prostate cancer (Smith et al., Science 274:1371, 1996). Since this finding multiple other HPC loci have been identified, including our finding of the HPCX locus at Xq27-28 (Xu et al. Nat. Gen. 20:175, 1998). These results emphasize the genetic heterogeneity that characterizes HPC. To increase the power of our family collection in an effort to deal with this heterogeneity, we have collected an additional 57 HPC families, each having over 4 individuals affected with prostate cancer. We have carried out genotypic analysis of our complete collection of 175 pedigrees at a series of putative HPC loci, including loci implicated by other research groups on chromosomes 1, 8, 20 and 17 (HPC2). While little evidence of linkage was found at this latter locus, novel loci were identified on both chromosomes 1 and 8. By accumulating linkage data on our complete set of HPC families, we are able to begin to understand and evaluate genetic heterogeneity of HPC, as well as to provide critical positional information for gene mapping and identification studies. Such studies are prerequisite to the development of genetic tests for determination of prostate cancer susceptibility.