We propose to establish a multidisciplinary team of epidemiologists, statisticians, basic scientists and clinician scientists to promote and pursue thorough identification and characterization of genomic loci associated with prostate cancer. ELLIPSE (ELucidating Loci Involved in Prostate cancer SuscEptibility) is a translational grant comprised of three highly integrated projects. Project 1 aims to take advantage of existing and shortly to be completed GWAS of prostate cancer in European, African American, Latino and Japanese populations to discover novel risk loci, and to rigorously replicate these associations in large existing consortia of prostate cases and controls (PRACTICAL, BPC3, and MADCaP). A major focus of this expanded effort is to identify loci that may selectively be associated with advanced disease and variants that contribute to ethnic difference in disease risk. Selective fine mapping of risk loci will also be performed to comprehensively characterize the relevant allelic locus, utilizing all available data on common variants from Hapmap, selective sequencing efforts, and from the 1000 Genome Project. Project 2 is focused on understanding the gene(s) that the non-protein coding risk variants are acting through. Two hypotheses will be systematically explored using a wide variety of established and emerging techniques: the risk loci harbor as yet undetected transcripts (either coding or non-coding) and the risk loci are regulatory elements. Finally, in Project 3 we propose to investigate the potential of this new knowledge on the genetic basis of prostate cancer susceptibility to enhance risk assessment, through gene-gene and gene-environment interactions, and importantly, to provide the potential for novel clinical practices through impacts on cancer diagnosis and treatment, or newer cancer prevention strategies. The overarching goal is to discover the pathways that drive prostate cancer pathogenesis and to assess their role in clinical decision making.

Public Health Relevance

The discovery of novel risk alleles for prostate cancer will provide new insights into biological pathways that are important in the development of prostate cancer, particularly aggressive disease. This insight into prostate cancer biology will disclose novel targets for chemopreventive and therapeutic interventions and may reveal approaches to primary prevention.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19CA148537-02
Application #
8110487
Study Section
Special Emphasis Panel (ZCA1-SRLB-4 (J1))
Program Officer
Gillanders, Elizabeth
Project Start
2010-07-13
Project End
2014-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
2
Fiscal Year
2011
Total Cost
$2,539,039
Indirect Cost
Name
University of Southern California
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
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