Prostate is the most common site of cancer in men in the United States. Most prostate cancers progress relatively slowly and stay confined within the prostate. However, some cases grow aggressively and metastasize to other parts of the body. The most important clinical challenge in the treatment of the disease is the not knowing which of these two clinical forms a patient is presenting with. This is critically important information given the significant morbidity associated with treatment interventions and could eventually help distinguish men who need intensive treatment from those who may be better served by watchful waiting. Currently, the level of serum PSA, clinical stage and Gleason score are used to estimate prognosis and inform treatment modalities. Although they are very useful, additional biomarkers may help to better predict the outcome of prostate cancer. Carefully designed molecular epidemiologic studies can contribute in this arena. Although the significance of angiogenesis in prostate cancer is demonstrated by its correlation with clinical features, such as clinical stage, Gleason scores, progression, metastasis and survival, relatively few studies have assessed the role of genes involved in the angiogenesis pathway with recurrence of prostate cancer. Research to identify the specific genes and genetic variants relevant to angiogenesis risk remain largely unexplored. Part of the reason why candidate gene studies have been inconclusive may be that a major source of genetic regulation has been ignored: gene silencing through DNA methylation. Our hypothesis is that genetic and epigenetic individual variation in genes involved in the angiogenesis pathway is associated with recurrence of prostate cancer. The ultimate goal of this study is to identify biomarkers that can be used at the time of diagnosis to predict prognosis and improve clinical treatment decision making. The proposed study involves (1) construction of a historical cohort of prostate cancer cases (n=~1300) treated with radical prostatectomy at the H. Lee Moffitt Cancer Center between 1987 and 2003, (2) evaluating the association between 802 SNPs in 52 genes involved in angiogenesis with risk of recurrent prostate cancer, (3) evaluating the association between DNA methylation in the promoter regions of angiogenesis genes and risk for recurrence of prostate cancer and (4) testing the combined effects of inherited and acquired genetic changes in the candidate genes on disease aggressiveness.
These studies will provide key information regarding the potential effect of epigenetic genetic variations on prostate cancer recurrence. The combination of the individual's epigenetic and genetic profile and a current prediction model can possibly estimate a more accurate recurrence risk of the prostate cancer patients. This model can be extremely useful for a strategy of prostate cancer treatment.
|Lin, Hui-Yi; Chen, Dung-Tsa; Huang, Po-Yu et al. (2017) SNP interaction pattern identifier (SIPI): an intensive search for SNP-SNP interaction patterns. Bioinformatics 33:822-833|
|Strand, Siri H; Switnicki, Michal; Moller, Mia et al. (2017) RHCG and TCAF1 promoter hypermethylation predicts biochemical recurrence in prostate cancer patients treated by radical prostatectomy. Oncotarget 8:5774-5788|
|Saunders, Edward J; Dadaev, Tokhir; Leongamornlert, Daniel A et al. (2016) Gene and pathway level analyses of germline DNA-repair gene variants and prostate cancer susceptibility using the iCOGS-genotyping array. Br J Cancer 114:945-52|
|Das, Dibash K; Osborne, Joseph R; Lin, Hui-Yi et al. (2016) miR-1207-3p Is a Novel Prognostic Biomarker of Prostate Cancer. Transl Oncol 9:236-41|
|Lin, Hui-Yi; Cheng, Chia-Ho; Chen, Dung-Tsa et al. (2016) Coexpression and expression quantitative trait loci analyses of the angiogenesis gene-gene interaction network in prostate cancer. Transl Cancer Res 5:S951-S963|
|Gusev, Alexander; Shi, Huwenbo; Kichaev, Gleb et al. (2016) Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation. Nat Commun 7:10979|
|Stegeman, Shane; Amankwah, Ernest; Klein, Kerenaftali et al. (2015) A Large-Scale Analysis of Genetic Variants within Putative miRNA Binding Sites in Prostate Cancer. Cancer Discov 5:368-79|
|Long, Qi; Xu, Jianpeng; Osunkoya, Adeboye O et al. (2014) Global transcriptome analysis of formalin-fixed prostate cancer specimens identifies biomarkers of disease recurrence. Cancer Res 74:3228-37|
|Al Olama, Ali Amin; Kote-Jarai, Zsofia; Berndt, Sonja I et al. (2014) A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. Nat Genet 46:1103-9|
|Amankwah, Ernest K; Anegbe, Evelyn; Park, Hyun et al. (2013) miR-21, miR-221 and miR-222 expression and prostate cancer recurrence among obese and non-obese cases. Asian J Androl 15:226-30|
Showing the most recent 10 out of 25 publications