Prostate cancer is a common but complex disease with a number of unresolved issues surrounding its natural history. These include concerns with screening, detection, and treatment, and reflect the substantial heterogeneity in prostate tumors: some will remain latent and have little impact on morbidity, whereas others progress rapidly in a potentially lethal manner. Genetic factors likely underlie some of these differences, and we propose a comprehensive evaluation of the genetic basis of prostate cancer risk and progression in a large, well-characterized study population. In particular, we will investigate rar functional variants across the exome and common SNPs across the genome. Our sample encompasses 8,078 prostate cancer cases and 8,078 age and ethnicity matched controls nested within the Kaiser / USCF Research Program on Genes, Environment and Health cohort. This population has existing genome-wide SNP measures, and uniformly collected clinical information on prostate cancer screening, diagnoses, and progression. We plan to type the new exome array on the cases and controls to assess the functional variants in protein coding regions across the human genome. With these data we will address our hypothesis that these genetic factors can be used to predict-and underlie an increasing proportion of the variation in-prostate cancer risk and progression. This project provides an efficient and innovative opportunity to obtain a comprehensive understanding of how these factors impact the natural history of prostate cancer. Our findings should supply important insights into the underlying mechanism of disease, with the ultimate goal of helping to improve screening and treatment for prostate cancer.

Public Health Relevance

Prostate cancer is one of the most common and clearly genetic cancers, but finding the mechanisms underlying the natural history of this disease has proven difficult. Our efforts toward deciphering the genetic basis of prostate cancer will help improve screening, treatment, and our understanding of this disease, all important goals of the overall National Cancer Institute's Mission. These advances will improve the overall health of men, providing much needed information about individual and population-level risks of prostate cancer development and progression.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA088164-12A1
Application #
8519926
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Elena, Joanne W
Project Start
2000-09-01
Project End
2016-06-30
Budget Start
2013-07-15
Budget End
2014-06-30
Support Year
12
Fiscal Year
2013
Total Cost
$523,491
Indirect Cost
$102,058
Name
University of California San Francisco
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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