The goal of this proposal is to identify and characterize prostate cancer susceptibility loci. In order to accomplish this task we will: 1) ascertain and collect DNA samples from large prostate cancer kindreds, 2) test each kindred for linkage to candidate regions for prostate cancer susceptibility loci, 3) perform a genomic search for prostate cancer susceptibility loci for kindreds unlinked to candidate loci, 4) create a fine structure map around the susceptibility loci identified, and 5) characterize the abnormal phenotype of individuals with linked susceptibilities. The unique characteristics of the Utah population for genetic analysis will be an essential asset. Utah currently has the most informative set of breast cancer kindreds (in terms of LOD score) in the entire community; and a similar mapping study in 10 Utah kindreds identified the 9p melanoma susceptibility locus (Cannon-Albright et al., 1992). We will ascertain and study large Utah kindreds likely to carry prostate cancer susceptibility loci, analyze them for linkage with candidate loci; and screen them with a series of short tandem repeat markers (STRs) to identify possible susceptibility loci in a general linkage search. For newly identified prostate cancer susceptibility loci, we will identify key recombinants in these large kindreds and use them to create a fine structure map around the susceptibility locus. When necessary, new STR markers will be developed to aid in this effort. Both affected and unaffected carriers of an inherited susceptibility will be identified through linkage analysis. We will use these gene carriers to characterize the phenotypic effect of each identified prostate cancer susceptibility locus. Actual cloning of any susceptibility genes identified is anticipated to be funded separately.
| Tavtigian, S V; Simard, J; Teng, D H et al. (2001) A candidate prostate cancer susceptibility gene at chromosome 17p. Nat Genet 27:172-80 |
| Verhagen, P C; Zhu, X L; Rohr, L R et al. (2000) Microdissection, DOP-PCR, and comparative genomic hybridization of paraffin-embedded familial prostate cancers. Cancer Genet Cytogenet 122:43-8 |
| Neuhausen, S L; Farnham, J M; Kort, E et al. (1999) Prostate cancer susceptibility locus HPC1 in Utah high-risk pedigrees. Hum Mol Genet 8:2437-42 |
| Neuhausen, S L; Skolnick, M H; Cannon-Albright, L (1997) Familial prostate cancer studies in Utah. Br J Urol 79 Suppl 1:15-20 |
