Prostate cancer is the second leading cause of death by cancer among males in the United States.? Both genetic and environmental factors are likely to contribute to both the risk for development of the? disease as well as the progression of the tumors once established. During the past funding cycle our? group has made the novel observation that some individuals carry a deletion polymorphism of the? gene, UGT2B17 that encodes an enzyme shown to be capable of inactivation of androgens. Our? overall hypothesis underlying this project is that an individual carrying fewer than two copies of? UGT2B17 would have higher tissue androgen levels because of decreased catabolism. Since? androgens are well known as growth factors for prostate cells, we hypothesize that this deletion? polymorphism would confer risk for development of prostate cancer. To begin to address this question? we will carry out two different lines of investigation. First, in aim one and two, we propose to? characterize the polymorphism present in the human population, defining the deletion event from which? it arose and it current frequency in different human populations. Importantly, we determine whether? this deletion is in linkage disequilibrium with polymorphisms in linked genes capable of metabolizing? androgens. This will provide the groundwork for population studies determining association between? the mutant UGT2B17 gene and incidence, severity and survival from prostate cancer. Secondly, we? will establish the contribution of UGT2B17to the metabolism of androgens using a number of tissue? culture cells lines manipulated to express different levels of this enzyme. This will provide functional? bases for the genetic studies proposed.
| Grant, Delores J; Hoyo, Cathrine; Oliver, Shannon D et al. (2013) Association of uridine diphosphate-glucuronosyltransferase 2B gene variants with serum glucuronide levels and prostate cancer risk. Genet Test Mol Biomarkers 17:3-9 |
| Vidal, Adriana C; Tucker, Cocoa; Schildkraut, Joellen M et al. (2013) Novel associations of UDP-glucuronosyltransferase 2B gene variants with prostate cancer risk in a multiethnic study. BMC Cancer 13:556 |
| Pointer, Mildred A; Daumerie, Geraldine; Bridges, LaKessha et al. (2012) Physiological stress increases renal injury in eNOS-knockout mice. Hypertens Res 35:318-24 |
| Vidal, Adriana C; Grant, Delores J; Williams, Christina D et al. (2012) Associations between Intake of Folate, Methionine, and Vitamins B-12, B-6 and Prostate Cancer Risk in American Veterans. J Cancer Epidemiol 2012:957467 |
| Daumerie, Geraldine; Bridges, Lakeesha; Yancey, Sadiqa et al. (2010) The effect of salt on renal damage in eNOS-deficient mice. Hypertens Res 33:170-6 |
| Carney, Skyla T; Lloyd, Michael L; MacKinnon, Shanta E et al. (2009) Cannabinoid regulation of nitric oxide synthase I (nNOS) in neuronal cells. J Neuroimmune Pharmacol 4:338-49 |
| Gerald, Tonya M; Howlett, Allyn C; Ward, Gregg R et al. (2008) Gene expression of opioid and dopamine systems in mouse striatum: effects of CB1 receptors, age and sex. Psychopharmacology (Berl) 198:497-508 |
| Jones, Jenelle D; Carney, Skyla T; Vrana, Kent E et al. (2008) Cannabinoid receptor-mediated translocation of NO-sensitive guanylyl cyclase and production of cyclic GMP in neuronal cells. Neuropharmacology 54:23-30 |
| Howlett, Allyn C; Mukhopadhyay, Somnath; Norford, Derek C (2006) Endocannabinoids and reactive nitrogen and oxygen species in neuropathologies. J Neuroimmune Pharmacol 1:305-16 |
| Wilson 3rd, Willie; Pardo-Manuel de Villena, Fernando; Lyn-Cook, Beverly D et al. (2004) Characterization of a common deletion polymorphism of the UGT2B17 gene linked to UGT2B15. Genomics 84:707-14 |
