Grant Details
Grant Number: |
3R01CA068581-04S1 Interpret this number |
Primary Investigator: |
Reichardt, Juergen |
Organization: |
University Of Southern California |
Project Title: |
5alpha Reductase Genotype, Race and Prostate Cancer Risk |
Fiscal Year: |
1998 |
Abstract
Prostate cancer is diagnosed in almost 200,000 men every year in the US
and accounts for about 38,000 annual deaths. In this application, we
intend to take a molecular epidemiologic approach to examining our central
hypothesis that risk of prostate cancer is substantially influenced by
specific genotypes in the human 5alpha-reductase type II (SRD5A2) gene.
We propose to investigate the following seven specific aims with molecular
genetic and epidemiologic tools: 1) To determine the relationship between
the SRD5A2 gene and prostate cancer by genotyping a particular polymorphic
DNA marker [TA short tandem repeat (TA-STR)] in the SRD5A2 gene in men
with prostate cancer and matched controls from African-American and White
men at widely different risks of prostate cancer. 2) To characterize DNA
sequence variations in the SRD5A2 gene that predispose men to prostate
cancer by sequencing DNA from a small number of African-American and White
men with prostate cancer, who carry the high risk SRD5A2 genotypes
identified in (1), and so to determine the precise nature of the germline
DNA alterations predisposing to prostate cancer. 3) To characterize DNA
sequence variations in the SRD5A2 gene that may protect Asian men from
prostate cancer by sequencing DNA from a small number of normal (control)
Asian men who have low levels of dihydrotestosterone (DHT), and so to
determine the germline DNA alterations which may be protective against
prostate cancer. 4) To determine the biochemical properties (enzyme
activity) of each sequence variation identified in (2) and (3). This will
distinguish irrelevant polymorphisms from actual activity altering
mutations. 5) To determine the relationship between the SRD5A2 gene and
prostate cancer by genotyping [using the relevant sequence variations
identified in (4)] the SRD5A2 gene in three racial-ethnic groups [Asian-
Americans (defined here as Chinese- and Japanese-Americans), African-
Americans and Whites] of prostate cancer cases and matched controls. 6) To
utilize the results on the strength of the associations identified in (5)
and the prevalence of these alleles in the three racial-ethnic groups, to
estimate the contribution of SRD5A2 genotype in explaining the variation
in prostate cancer risk among these three groups of men at widely
differing risk of prostate cancer. 7) To further characterize the
involvement of the SRD5A2 gene in prostate cancer by defining somatic
mutations in this gene.
Publications
None. See parent grant details.