||5R01CA084989-04 Interpret this number
||Wayne State University
||Polymorphisms in Prostate Cancer Carcinogenesis
DESCRIPTION (Adapted from applicant's abstract): Incidence and mortality rates
for prostate cancer among African-American men in Detroit are among the highest
in the world. The extraordinary impact of this disease on our community has led
to the development of several large NIH funded research studies of prostate
cancer. Two of these studies focus on the etiology of prostate cancer. One, a
study of the frequency and extent of prostatic intraepithelial neoplasia and
latent prostate cancer at autopsy of sudden death victims, documents
frequencies of the earliest microscopic precursors of prostate cancer. The
second, a population-based case-control study, characterizes determinants of
clinical disease. The autopsy study includes over 600 subjects cases and the
case-control study over 700 cases and an equivalent number of controls. Both
include a high proportion of African-American men. Although extensive, these
studies do not address the role of genetic susceptibility in the etiology of
prostate cancer. Recent studies reporting associations between genetic
polymorphisms and prostate cancer risk provide important opportunities for
determining the etiology of prostate cancer using the data and tissue resources
from our ongoing studies. The polymorphisms include factors governing the
biological effects of androgens, (polymorphisms in the androgen receptor gene
itself and enzymes determining the synthesis and degradation of active forms of
testosterone) and the biological effectiveness of vitamin D (polymorphisms in
the receptor). Analysis of specimens from our ongoing studies will allow
investigations of the impact of these polymorphisms on both the earliest
detectable phase of prostate cancer in the autopsy study and its progression to
clinical disease in the case-control study. Our analysis will emphasize
comparisons of findings for African-American and Caucasian males from the same
community. This project will provide a valuable opportunity to define the role
of the individual effects and the interplay of androgens, vitamin D, and race
in the etiology of prostate cancer, and to distinguish their effects on its
preclinical initiation and progression to clinical disease.
Impact of a genetic variant in CYP3A4 on risk and clinical presentation of prostate cancer among white and African-American men.
Bangsi D, Zhou J, Sun Y, Patel NP, Darga LL, Heilbrun LK, Powell IJ, Severson RK, Everson RB
Urol Oncol, 2006 Jan-Feb;24(1), p. 21-7.
Common EGFR mutations conferring sensitivity to gefitinib in lung adenocarcinoma are not prevalent in human malignant mesothelioma.
Cortese JF, Gowda AL, Wali A, Eliason JF, Pass HI, Everson RB
Int J Cancer, 2006 Jan 15;118(2), p. 521-2.
The impact of CAG repeats in exon 1 of the androgen receptor on disease progression after prostatectomy.
Powell IJ, Land SJ, Dey J, Heilbrun LK, Hughes MR, Sakr W, Everson RB
Cancer, 2005 Feb 1;103(3), p. 528-37.
CYP3A4 genetic variant and disease-free survival among white and black men after radical prostatectomy.
Powell IJ, Zhou J, Sun Y, Sakr WA, Patel NP, Heilbrun LK, Everson RB
J Urol, 2004 Nov;172(5 Pt 1), p. 1848-52.