Identification and confirmation of new genetic variants that explain the genetic susceptibility of prostate cancer
This study focuses on 120 families with hereditary prostate cancer (HPC).
Family studies, fine mapping of chromosomal regions identified in linkage studies
Most of the work is done within the ICPCG and currently we are conducting a genome wide scan of 70 Swedish HPC families using the Illumina Linkage SNP chip (7000 SNPs). We will analyze the Swedish families both separately and jointly with an additional 1,000 international HPC families. In addition we are planning fine mapping with micro-satellites and SNPs on chromosome 5q11.2 and 19p13.3 20 using all 120 families and the CAPS population.
Systematic analysis in of genetic variants in genes in selected for prostate cancer important biological pathways, for example inflammation and sex steroid hormones. Based on the systematic replication of reported genetic association, we have strong support for the importance of androgen pathway genes in prostate cancer etiology. Based on these results we are genotyping total 40 htSNPs in the AR, SDR5A2 and CYP17 genes in CAPS (5000 individuals). To further explore if genetic variation in hormone pathways is important in prostate cancer, using published information and bioinformatics to identify htSNPs, we will select htSNPs in about 70 genes (~750 SNPs total). These SNPs will be genotyped on the Illumina system in CAPS1. SNPs that are significant (p<0.05) in caps1 will be analyzed in caps2 in order to replicate our finding.
Genome Wide SNP Scan
Using Affymetrix 550K SNP chip in a multi-stage design. In collaboration with Dr Xu at Wake Forest, Dr Isaccs at Johns Hopkins and Dr Jeff Trent at TGEN (Az) we are planning a genome wide SNP scan using the CAPS population.