Genomic and Functional Analysis of UGT2B17 in Prostate Cells

North Carolina Central University, Durham NC

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Abstract

Prostate cancer is the second leading cause of death by cancer among males in the United States.[unreadable] Both genetic and environmental factors are likely to contribute to both the risk for development of the[unreadable] disease as well as the progression of the tumors once established. During the past funding cycle our[unreadable] group has made the novel observation that some individuals carry a deletion polymorphism of the[unreadable] gene, UGT2B17 that encodes an enzyme shown to be capable of inactivation of androgens. Our[unreadable] overall hypothesis underlying this project is that an individual carrying fewer than two copies of[unreadable] UGT2B17 would have higher tissue androgen levels because of decreased catabolism. Since[unreadable] androgens are well known as growth factors for prostate cells, we hypothesize that this deletion[unreadable] polymorphism would confer risk for development of prostate cancer. To begin to address this question[unreadable] we will carry out two different lines of investigation. First, in aim one and two, we propose to[unreadable] characterize the polymorphism present in the human population, defining the deletion event from which[unreadable] it arose and it current frequency in different human populations. Importantly, we determine whether[unreadable] this deletion is in linkage disequilibrium with polymorphisms in linked genes capable of metabolizing[unreadable] androgens. This will provide the groundwork for population studies determining association between[unreadable] the mutant UGT2B17 gene and incidence, severity and survival from prostate cancer. Secondly, we[unreadable] will establish the contribution of UGT2B17to the metabolism of androgens using a number of tissue[unreadable] culture cells lines manipulated to express different levels of this enzyme. This will provide functional[unreadable] bases for the genetic studies proposed.