Identification of Novel, Inherited Genetic Markers for Aggressive PCa in European and African Americans Using Whole Genome Sequencing
Annual rept. 22 Aug 2011-21 Aug 2012
WAKE FOREST UNIV WINSTON-SALEM NC SCHOOL OF HEALTH SCIENCES
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Prostate cancer PCa is the most common cancer and the second leading cause of cancer death among men in the United States. While most prostate cancer PCa patients have an indolent form of the disease that may not even require treatment, about 10-15 of PCa patients have an aggressive form that may progress to metastases and death thus requiring intensive treatment. Several clinical variables such as PSA levels, Gleason grade, and TNM stage are good predictors for disease with poor clinical outcomes however, their predictive performance needs to be improved. Our inability to reliably distinguish between these two forms of PCa, early on in the course of the disease has resulted in the over-treatment of many and under treatment of some. The identification of additional markers, including genetic variants will improve our ability to distinguish aggressive from indolent forms of PCa and to better understand the racial disparity of PCa that exists between EAs and AAs. In this DOD proposal, we hypothesized that multiple rare sequence variants in the genome may increase aggressive PCa risk. Through a genome-wide search of rare variants based on an existing population from Johns Hopkins Hospital JHH of 400 aggressive PCa and 400 indolent PCa using Illumina Human Exome BeadChip, we identified several rare variants that are significantly associated with aggressive PCa development in EA or AA populations. The implicated rare variants will be followed in additional populations.
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