Prostate cancer (CAP) is the most frequently diagnosed solid tumor and the second leading cause of cancer deaths among U.S. men. Despite the substantial morbidity and mortality associated with CaP, limited attention has been focused on elucidation of factors that predict clinical disease progression or mortality. Environmental and genetic factors may play a role in the development of aggressive, life-threatening CaP. We hypothesize that variant alleles in genes involved in the androgen/growth factor/antioxidant pathways confer a higher risk for disease progression and mortality. Specifically, we propose to genotype a population-based cohort of CaP patients to address the following hypotheses: 1) Heterozygotes and homozygotes for the valine allele (V89L) in the SRD5A2 gene have an increased risk of prostate cancer progression and mortality; 2) Heterozygotes and homozygotes for the threonine allele (A49T) in the SRD5A2 gene have an increased risk of prostate cancer progression and mortality; 3) Homozygosity for the C allele (polymorphism -202) in the insulin-like growth factor-binding protein-3 (IGFBP-3) gene is associated with an increased risk of prostate cancer progression and mortality; 4) Homozygosity for the A allele (polymorphism -9) in the MnSOD gene is associated with an increased risk of prostate cancer progression and mortality. The study will take advantage of extensive interview and clinical data previously collected on 753 CaP patients diagnosed between 1993-1996 and followed for 10-13 years (through 2006). Stored genomic DNA (n625) will be used for genetic analysis of these patients. Follow-up patient surveys, physician surveys, medical record reviews, and linkage with the Seattle SEER cancer registry will be used to identify patients with disease progression or death (all cause, prostate cancer-specific). Cox proportional hazards models will be used to assess genotype-Cap outcomes. As secondary aims, we will: 1) assess each measure of clinical progression (symptomatic, radiologic, biochemical) by genotype; 2) assess whether clinical or pathologic tumor characteristics at diagnosis vary by genotype; and, 3) utilize the ost/lifestyle/environmental data to examine whether Cap outcomes vary by factors such as family history of prostate cancer, body mass index, or dietary intake. This study may identify genetic variants that are useful for the stratification of Cap patients into high-risk progression/mortality subgroups who may thus benefit from aggressive therapy and clinical trials of new adjuvant therapies. Results may also increase our understanding of the underlying molecular biology and genetic epidemiology of this common, life-threatening disease.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
1P50CA097186-01
Application #
6671813
Study Section
Special Emphasis Panel (ZCA1)
Project Start
2002-09-19
Project End
2007-04-30
Budget Start
Budget End
Support Year
1
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109
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