Collection of Prostate Cancer Families and Mapping Additional Hereditary Prostate Cancer Genes (HPC2, HPC3,...)
Annual rept. 1 Oct 1999-30 Sep 2000
JOHNS HOPKINS UNIV BALTIMORE MD SCHOOLOF MEDICINE
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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 HPCl locus at 1q24-25 as the first reported linkage in prostate cancer Smith et al., Science 2741371, 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. 20175, 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 propose to collect an additional 57 HPC families, each having over 4 individuals affected with prostate cancer. To date we have collected 53 of these families and we have carried out genotypic analysis of these and our existing families at a series of putative HPC loci, including loci implicated by other research groups on chromosomes 1 and 8. Novel loci have been implicated on both of these chromosomes. By accumulating linkage data on our complete set of over 170 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.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research