Grant Details
Grant Number: |
3R01CA085914-02S1 Interpret this number |
Primary Investigator: |
Schwartz, Stephen |
Organization: |
Fred Hutchinson Cancer Research Center |
Project Title: |
Molecular Epidemiology of Testicular Carcinoma |
Fiscal Year: |
2002 |
Abstract
DESCRIPTION (Adapted from the Applicant's Abstract): The incidence of
testicular germ cell carcinoma (TGCC), the most common malignancy developing in
young men, has increased several-fold since the 1950s. Despite three decades of
research in human populations, the etiology of TGCC remains obscure and our
knowledge of risk factors is limited largely to demographic characteristics and
a history of undescended testes. Clinical, non-human experimental, and
epidemiologic studies of TGCC have provided evidence that exposure to abnormal
levels of steroid hormones, either in utero, perinatally, and/or early in life,
may be a key etiologic factor for TGCC. Epidemiologic support of this
hypothesis, however, has been inconsistent, a phenomena attributable at least
in part to the limited ability of interview and medical record data to capture
the relevant exposures. Recent progress in identifying polymorphisms in genes
contributing to endogenous steroid hormone metabolism presents an opportunity
to expand beyond the scope of prior epidemiologic studies by addressing the
hypothesized hormonal etiology of TGCC at the molecular genetic level.
Specifically, we propose to test the hypothesis that inherited variation in
genes involved in stimulating testicular steroidogenesis, synthesizing and
metabolizing testosterone, and androgen signaling, is related to the risk of
developing TGCC.
A population-based case-control study will be conducted. Cases will be
approximately 280 incident cases of TGCC diagnosed between October 1998 and
September 2003 and who are residents of a three county metropolitan region in
western Washington State. Demographically similar controls (n=840) will be
ascertained from the general population using random digit telephone dialing.
Cases and controls will be interviewed in-person regarding medical and
lifestyle histories. A venous blood sample will be obtained from all consenting
participants and peripheral leukocytes isolated and stored. Genomic DNA
extracted from leukocytes will be tested for variants in the following genes
involved in 1) the stimulation of testicular steroidogenesis (Luteinizing
Hormone and Insulin-Like Growth Factor-1), 2) the synthesis and metabolism of
testosterone (Cytochrome p450 11a [CYP11a], CYP17, 3Beta-Hydroxysteroid
Dehydrogenase Type II, CYP3A4, and UDP-Glucuronosyltransferase 2B15), and 3)
testosterone signaling (Androgen Receptor). Cases and controls will be compared
with respect to the prevalence of putative "high risk" genotypes and alleles
for each gene. The sample size also will provide sufficient statistical power
to identify interaction between high-risk genotypes. The findings from this
study therefore will add new information regarding the epidemiology and
etiology of TGCC, and will serve as a resource for future investigations of
genetic associations.
Publications
None. See parent grant details.