"Cloning Genes for Susceptibility to Breast and Prostate Cancer"
Epidemiological and genetic data support the existence of genes that predispose jointly to breast and prostate cancer. The goal of this project is to build upon a recently completed genome wide scan of 254 high risk prostate cancer families, 67 of whom also have a first-degree realtive with breast cancer, to clone such susceptibility genes. We will first assign priorities for follow-up of initial linkage results by consideration of data derived from the entire data set, as well as stratified subsets of families grouped by age at onset, family history, and clinical features of disease. Once loci of interest are prioritized, we will define a minimum critical region for each by genotyping additional markers and identifying recombinants relative to markers and known genes. A physical map of BACs across regions of interest will be constructed using publicly available data, with gaps filled in my additional screening as needed. Final selection of candidate genes will be made using mapping, functional, and publicly available expression data. These genes will be analyzed for disease-associated mutations and polymorphisms, including SNPs, in the 254 family data set and, if appropriate, in a population-based cohort. The resulting data will provide information about the type and distribution of disease causing mutations in high-risk families and populations.
The proposed study is a new project of these mentors whose previous collaborations have focused on genetic mapping and candidate gene analysis. The dual environment provides a unique opportunity for integration of distinct approaches to finding putative cancer genes and deciphering their importance in high-risk families and the general population. In addition, it provides the trainee with a full set of tools for tackling similar problems, independently, in the future.