LOCALIZATION OF SUSCEPTIBILITY LOCI IN PROSTATE CANCER

Project: Research project

Project Details

Description

DESCRIPTION (Adapted from investigator's abstract): Prostate cancer is one of
the most common malignancies of males in western countries, accounting for 36
percent of all male cancers and 13 percent of male cancer-related deaths. In
spite of the magnitude of the problem which this malignancy presents, an
understanding of the molecular mechanisms underlying susceptibility remains
elusive. Complex segregation analyses suggest the existence of dominant
high-penetrant susceptibility alleles, which may account for up to 10 percent
of all prostate cancer. During this past grant period, the applicant has
performed a genome-wide scan on 163 kindreds with three or more affected men
with prostate cancer, as well as analyzed several chromosomal regions reported
by others to demonstrate linkage. By the end of the current grant period, they
will have completed the genome-wide scan of their families. Although linkage
analysis of hereditary prostate cancer (HPC) is complicated by a number of
barriers, including potentially extensive genetic heterogeneity, high phenocopy
rates, and lack of fully informative pedigrees, a number of research groups
(including the Mayo Clinic) have implicated four loci (three on chromosome 1
and one on the X chromosome) as harboring HPC genes. Additionally, the P.I. has
demonstrated linkage to an unreported region on chromosome 20, at 20q13. In
spite of the progress made, these five loci still account for less than half of
the HPC cases. With the completion of the genome-wide scan, as well as the
completion of similar analyses from other groups, it is likely that other
chromosomal regions will be identified. It is noticed that none of the putative
susceptibility genes from these regions have been identified. Thus, the P.I.
proposed the following specific aims: 1) Complete the statistical analysis of
the genome-wide scan and identify additional regions of linkage for more
detailed analyses; 2) Define the narrowest genetic and physical interval for
those regions demonstrating the strongest evidence of linkage in the Mayo
families; 3) Identify candidate genes that map to these region(s), especially
to chromosome 20ql3; and 4) Analyze and characterize genes from the regions of
interest for their involvement in hereditary prostate cancer. The potential
impact of the discoveries of cancer susceptibility genes on cancer prevention
and early detection, leading to increased likelihood of cure is great. In the
case of prostate cancer, it is clear that early, localized disease is highly
curable.
StatusFinished
Effective start/end date12/26/9611/30/07

ASJC

  • Medicine(all)