DESCRIPTION (Adapted from investigator's abstract): Prostate cancer is
the most common cancer and the second leading cause of cancer deaths
among men in the United States. Approximately 334,500 men are diagnosed
every year. Despite advances in treatment and increased screening
efforts, about 41,800 men each year will go on to die of the disease.
This is similar to the number of women that die yearly from breast
cancer.
Epidemiological data support the hypothesis that strong familial
components are involved in the etiology of prostate cancer, particularly
in men diagnosed at young age or men with a family history of disease.
Mapping and eventual cloning of such genes is likely to provide insight
into the molecular mechanisms critical for prostate cancer
susceptibility, and provide knowledge about the molecular mechanisms of
prostate cancer initiation. This submission proposes to map prostate
cancer susceptibility genes by taking advantage of an ongoing effort to
collect high risk prostate cancer families that has been undertaken by
Seattle investigators. This effort has led to the identification of a
large number of high risk prostate cancer families and subsequent
collection of DNA samples, epidemiologic and clinical data, and family
history information from eligible families.
Specifically, the proposal is to 1) Genotype 250 high risk prostate
cancer families with 387 microsatellite-based genetic markers that span
the human genome at 10cM resolution. 2) Perform linkage and
nonparametric analysis to identify regions of the genome likely to
contain prostate cancer susceptibility genes using the above genotyping
data. This will involve stratifying families by a number of criteria for
which they have collected data, such as age of onset, tumor grade and
stage, PSA level, and occurrence and incidence of other cancers. 3)
Expand the analysis of a prostate cancer susceptibility gene at 1q24-25
from 49 to 250 high risk families. Particular emphasis will be placed
on heterogeneity analysis to best determine the subset of families for
which this locus is likely to be most significant. Finally, once regions
of the genome likely to contain prostate cancer susceptibility genes are
localized, they will refine the region of interest by analysis of
additional markers and identification of recombinants. These experiments
will provide a foundation for subsequent physical mapping efforts and
candidate cDNA analysis.
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- The DCCPS Team.
