Collection of Prostate Cancer Families and Mapping Additional Hereditary Prostate Cancer Genes (HPC2, HPC3,...)
Abstract
Our initial genome wide search for linkage in multiplex prostate cancer families implicated 1q24-25 as harboring a major prostate cancer susceptibility gene (HPC1), although there was significant evidence for locus heterogeneity and at least 5 other loci were implicated as the sites of HPC genes. Using families ascertained in Phase I of this project, an additional HPC locus located at Xq27-28 (HPCX) was identified. Furthermore we obtained strong preliminary evidence of an additional novel HPC locus on chromosome 8 that may account for up to 20% of all HPC families. To continue and extend these analyses towards the identification of the HPC genes on chromosomes X and 8, we proposed to narrow the gene-containing regions on Xq and 8p (from ^20 cM to 1-2 cM) using a variety of approaches including association studies in family and population based sample, and to assess candidate genes in regions delineated by these approaches by mutation screening. Our main focus has been on chromosome 8 where a number of candidate genes have been evaluated. Importantly, one gene, MSR1 at 8p22, was found to harbor clearly inactivating mutations, and other cancer-associated variants in HPC families and non-HPC cases. These results implicate for the first time genetic variation affecting macrophage function as an important determinant of inherited susceptibility for prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2003
- Accession Number
- ADA417342
Entities
People
- William B Isaacs
Organizations
- Johns Hopkins University