Grant Details
Grant Number: |
1R01CA128813-01A2 Interpret this number |
Primary Investigator: |
Park, Jong |
Organization: |
H. Lee Moffitt Cancer Ctr & Res Inst |
Project Title: |
Genetic & Epigenetic Analysis of Angiogenesis Genes in Recurrent Prostate Cancer |
Fiscal Year: |
2008 |
Abstract
DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.
Publications
NON-ADDITIVE EFFECTS OF COMMON GENETIC VARIANTS HAVE A NEGLIGENT CONTRIBUTION TO CANCER HERITABILITY.
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, Harrison T.A.
, Henning B.
, Turman C.
, Kraft P.
, Lindström S.
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Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2024-07-17 00:00:00.0; , .
EPub date: 2024-07-17 00:00:00.0.
PMID: 39018351
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Identification of blood protein biomarkers associated with prostate cancer risk using genetic prediction models: analysis of over 140,000 subjects.
Authors: Zhong H.
, Zhu J.
, Liu S.
, Ghoneim D.H.
, Surendran P.
, Liu T.
, Fahle S.
, Butterworth A.
, Ashad Alam M.
, Deng H.W.
, et al.
.
Source: Human Molecular Genetics, 2023-11-03 00:00:00.0; 32(22), p. 3181-3193.
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A saturated map of common genetic variants associated with human height.
Authors: Yengo L.
, Vedantam S.
, Marouli E.
, Sidorenko J.
, Bartell E.
, Sakaue S.
, Graff M.
, Eliasen A.U.
, Jiang Y.
, Raghavan S.
, et al.
.
Source: Nature, 2022 Oct; 610(7933), p. 704-712.
EPub date: 2022-10-12 00:00:00.0.
PMID: 36224396
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Novel strategy for disease risk prediction incorporating predicted gene expression and DNA methylation data: a multi-phased study of prostate cancer.
Authors: Wu C.
, Zhu J.
, King A.
, Tong X.
, Lu Q.
, Park J.Y.
, Wang L.
, Gao G.
, Deng H.W.
, Yang Y.
, et al.
.
Source: Cancer Communications (london, England), 2021-09-14 00:00:00.0; , .
EPub date: 2021-09-14 00:00:00.0.
PMID: 34520132
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A transcriptome-wide association study identifies novel candidate susceptibility genes for prostate cancer risk.
Authors: Liu D.
, Zhu J.
, Zhou D.
, Nikas E.G.
, Mitanis N.T.
, Sun Y.
, Wu C.
, Mancuso N.
, Cox N.J.
, Wang L.
, et al.
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Source: International Journal Of Cancer, 2021-09-14 00:00:00.0; , .
EPub date: 2021-09-14 00:00:00.0.
PMID: 34520569
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KLK3 SNP-SNP interactions for prediction of prostate cancer aggressiveness.
Authors: Lin H.Y.
, Huang P.Y.
, Cheng C.H.
, Tung H.Y.
, Fang Z.
, Berglund A.E.
, Chen A.
, French-Kwawu J.
, Harris D.
, Pow-Sang J.
, et al.
.
Source: Scientific Reports, 2021-04-29 00:00:00.0; 11(1), p. 9264.
EPub date: 2021-04-29 00:00:00.0.
PMID: 33927218
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Commercial Gene Expression Tests for Prostate Cancer Prognosis Provide Paradoxical Estimates of Race-Specific Risk.
Authors: Creed J.H.
, Berglund A.E.
, Rounbehler R.J.
, Awasthi S.
, Cleveland J.L.
, Park J.Y.
, Yamoah K.
, Gerke T.A.
.
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2020 01; 29(1), p. 246-253.
EPub date: 2019-11-22 00:00:00.0.
PMID: 31757784
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Tristetraprolin Is a Prognostic Biomarker for Poor Outcomes among Patients with Low-Grade Prostate Cancer.
Authors: Rounbehler R.J.
, Berglund A.E.
, Gerke T.
, Takhar M.M.
, Awasthi S.
, Li W.
, Davicioni E.
, Erho N.G.
, Ross A.E.
, Schaeffer E.M.
, et al.
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Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2018-08-14 00:00:00.0; , .
EPub date: 2018-08-14 00:00:00.0.
PMID: 30108099
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Snp Interaction Pattern Identifier (sipi): An Intensive Search For Snp-snp Interaction Patterns
Authors: Lin H.Y.
, Chen D.T.
, Huang P.Y.
, Liu Y.H.
, Ochoa A.
, Zabaleta J.
, Mercante D.E.
, Fang Z.
, Sellers T.A.
, Pow-Sang J.M.
, et al.
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Source: Bioinformatics (oxford, England), 2017-03-15 00:00:00.0; 33(6), p. 822-833.
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Can we eliminate neoadjuvant chemoradiotherapy in favor of neoadjuvant multiagent chemotherapy for select stage II/III rectal adenocarcinomas: Analysis of the National Cancer Data base.
Authors: Cassidy R.J.
, Liu Y.
, Patel K.
, Zhong J.
, Steuer C.E.
, Kooby D.A.
, Russell M.C.
, Gillespie T.W.
, Landry J.C.
.
Source: Cancer, 2017-03-01 00:00:00.0; 123(5), p. 783-793.
EPub date: 2016-10-25 00:00:00.0.
PMID: 27780316
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Rhcg And Tcaf1 Promoter Hypermethylation Predicts Biochemical Recurrence In Prostate Cancer Patients Treated By Radical Prostatectomy
Authors: Strand S.H.
, Switnicki M.
, Moller M.
, Haldrup C.
, Storebjerg T.M.
, Hedegaard J.
, Nordentoft I.
, Hoyer S.
, Borre M.
, Pedersen J.S.
, et al.
.
Source: Oncotarget, 2017-01-24 00:00:00.0; 8(4), p. 5774-5788.
PMID: 28052017
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PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS.
Authors: Southey M.C.
, Goldgar D.E.
, Winqvist R.
, Pylkäs K.
, Couch F.
, Tischkowitz M.
, Foulkes W.D.
, Dennis J.
, Michailidou K.
, van Rensburg E.J.
, et al.
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Source: Journal Of Medical Genetics, 2016 Dec; 53(12), p. 800-811.
PMID: 27595995
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Coexpression and expression quantitative trait loci analyses of the angiogenesis gene-gene interaction network in prostate cancer.
Authors: Lin H.Y.
, Cheng C.H.
, Chen D.T.
, Chen Y.A.
, Park J.Y.
.
Source: Translational Cancer Research, 2016 Oct; 5(Suppl 5), p. S951-S963.
PMID: 28664150
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Mir-1207-3p Is A Novel Prognostic Biomarker Of Prostate Cancer
Authors: Das D.K.
, Osborne J.R.
, Lin H.Y.
, Park J.Y.
, Ogunwobi O.O.
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Source: Translational Oncology, 2016 Jun; 9(3), p. 236-41.
PMID: 27267842
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Gene and pathway level analyses of germline DNA-repair gene variants and prostate cancer susceptibility using the iCOGS-genotyping array.
Authors: Saunders E.J.
, Dadaev T.
, Leongamornlert D.A.
, Al Olama A.A.
, Benlloch S.
, Giles G.G.
, Wiklund F.
, Gronberg H.
, Haiman C.A.
, Schleutker J.
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Source: British Journal Of Cancer, 2016-04-12 00:00:00.0; 114(8), p. 945-52.
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Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation.
Authors: Gusev A.
, Shi H.
, Kichaev G.
, Pomerantz M.
, Li F.
, Long H.W.
, Ingles S.A.
, Kittles R.A.
, Strom S.S.
, Rybicki B.A.
, et al.
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Source: Nature Communications, 2016-04-07 00:00:00.0; 7, p. 10979.
EPub date: 2016-04-07 00:00:00.0.
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Genome-wide association study of prostate cancer-specific survival.
Authors: Szulkin R.
, Karlsson R.
, Whitington T.
, Aly M.
, Gronberg H.
, Eeles R.A.
, Easton D.F.
, Kote-Jarai Z.
, Al Olama A.A.
, Benlloch S.
, et al.
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Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2015 Nov; 24(11), p. 1796-800.
EPub date: 2015-08-25 00:00:00.0.
PMID: 26307654
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A Large-Scale Analysis of Genetic Variants within Putative miRNA Binding Sites in Prostate Cancer.
Authors: Stegeman S.
, Amankwah E.
, Klein K.
, O'Mara T.A.
, Kim D.
, Lin H.Y.
, Permuth-Wey J.
, Sellers T.A.
, Srinivasan S.
, Eeles R.
, et al.
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Source: Cancer Discovery, 2015 Apr; 5(4), p. 368-79.
PMID: 25691096
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A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.
Authors: Al Olama A.A.
, Kote-Jarai Z.
, Berndt S.I.
, Conti D.V.
, Schumacher F.
, Han Y.
, Benlloch S.
, Hazelett D.J.
, Wang Z.
, Saunders E.
, et al.
.
Source: Nature Genetics, 2014 Oct; 46(10), p. 1103-9.
PMID: 25217961
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Global transcriptome analysis of formalin-fixed prostate cancer specimens identifies biomarkers of disease recurrence.
Authors: Long Q.
, Xu J.
, Osunkoya A.O.
, Sannigrahi S.
, Johnson B.A.
, Zhou W.
, Gillespie T.
, Park J.Y.
, Nam R.K.
, Sugar L.
, et al.
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Source: Cancer Research, 2014-06-15 00:00:00.0; 74(12), p. 3228-37.
EPub date: 2014-06-15 00:00:00.0.
PMID: 24713434
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Role Of P73 Dinucleotide Polymorphism In Prostate Cancer And P73 Protein Isoform Balance
Authors: Carastro L.M.
, Lin H.Y.
, Park H.Y.
, Kim D.
, Radlein S.
, Hampton K.K.
, Hakam A.
, Zachariah B.
, Pow-Sang J.
, Park J.Y.
.
Source: Prostate Cancer, 2014; 2014, p. 129582.
PMID: 25097786
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Chek2 (¿) 1100delc Mutation And Risk Of Prostate Cancer
Authors: Hale V.
, Weischer M.
, Park J.Y.
.
Source: Prostate Cancer, 2014; 2014, p. 294575.
PMID: 25431674
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miR-21, miR-221 and miR-222 expression and prostate cancer recurrence among obese and non-obese cases.
Authors: Amankwah E.K.
, Anegbe E.
, Park H.
, Pow-Sang J.
, Hakam A.
, Park J.Y.
.
Source: Asian Journal Of Andrology, 2013 Mar; 15(2), p. 226-30.
PMID: 23353719
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A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease.
Authors: Amin Al Olama A.
, Kote-Jarai Z.
, Schumacher F.R.
, Wiklund F.
, Berndt S.I.
, Benlloch S.
, Giles G.G.
, Severi G.
, Neal D.E.
, Hamdy F.C.
, et al.
.
Source: Human Molecular Genetics, 2013-01-15 00:00:00.0; 22(2), p. 408-15.
EPub date: 2013-01-15 00:00:00.0.
PMID: 23065704
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Global patterns of prostate cancer incidence, aggressiveness, and mortality in men of african descent.
Authors: Rebbeck T.R.
, Devesa S.S.
, Chang B.L.
, Bunker C.H.
, Cheng I.
, Cooney K.
, Eeles R.
, Fernandez P.
, Giri V.N.
, Gueye S.M.
, et al.
.
Source: Prostate Cancer, 2013; 2013, p. 560857.
PMID: 23476788
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SNP-SNP interaction network in angiogenesis genes associated with prostate cancer aggressiveness.
Authors: Lin H.Y.
, Amankwah E.K.
, Tseng T.S.
, Qu X.
, Chen D.T.
, Park J.Y.
.
Source: Plos One, 2013; 8(4), p. e59688.
PMID: 23593148
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Variation In Hnf1b And Obesity May Influence Prostate Cancer Risk In African American Men: A Pilot Study
Authors: Chornokur G.
, Amankwah E.K.
, Davis S.N.
, Phelan C.M.
, Park J.Y.
, Pow-Sang J.
, Kumar N.B.
.
Source: Prostate Cancer, 2013; 2013, p. 384594.
PMID: 24386569
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Genetic predictors of fatigue in prostate cancer patients treated with androgen deprivation therapy: preliminary findings.
Authors: Jim H.S.
, Park J.Y.
, Permuth-Wey J.
, Rincon M.A.
, Phillips K.M.
, Small B.J.
, Jacobsen P.B.
.
Source: Brain, Behavior, And Immunity, 2012 Oct; 26(7), p. 1030-6.
PMID: 22475653
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Gene variants in the angiogenesis pathway and prostate cancer.
Authors: Amankwah E.K.
, Sellers T.A.
, Park J.Y.
.
Source: Carcinogenesis, 2012 Jul; 33(7), p. 1259-69.
PMID: 22523086
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TRM: a powerful two-stage machine learning approach for identifying SNP-SNP interactions.
Authors: Lin H.Y.
, Chen Y.A.
, Tsai Y.Y.
, Qu X.
, Tseng T.S.
, Park J.Y.
.
Source: Annals Of Human Genetics, 2012 Jan; 76(1), p. 53-62.
PMID: 22150548
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DNA methylation in promoter region as biomarkers in prostate cancer.
Authors: Yang M.
, Park J.Y.
.
Source: Methods In Molecular Biology (clifton, N.j.), 2012; 863, p. 67-109.
PMID: 22359288
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Protein expressions and genetic variations of SLC5A8 in prostate cancer risk and aggressiveness.
Authors: Lin H.Y.
, Park H.Y.
, Radlein S.
, Mahajan N.P.
, Sellers T.A.
, Zachariah B.
, Pow-Sang J.
, Coppola D.
, Ganapathy V.
, Park J.Y.
.
Source: Urology, 2011 Oct; 78(4), p. 971.e1-9.
PMID: 21802122
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Multi-institutional prostate cancer study of genetic susceptibility in populations of African descent.
Authors: Taioli E.
, Flores-Obando R.E.
, Agalliu I.
, Blanchet P.
, Bunker C.H.
, Ferrell R.E.
, Jackson M.
, Kidd L.C.
, Kolb S.
, Lavender N.A.
, et al.
.
Source: Carcinogenesis, 2011 Sep; 32(9), p. 1361-5.
PMID: 21705483
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Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study.
Authors: Kote-Jarai Z.
, Olama A.A.
, Giles G.G.
, Severi G.
, Schleutker J.
, Weischer M.
, Campa D.
, Riboli E.
, Key T.
, Gronberg H.
, et al.
.
Source: Nature Genetics, 2011-07-10 00:00:00.0; 43(8), p. 785-91.
EPub date: 2011-07-10 00:00:00.0.
PMID: 21743467
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Prostate cancer predisposition loci and risk of metastatic disease and prostate cancer recurrence.
Authors: Ahn J.
, Kibel A.S.
, Park J.Y.
, Rebbeck T.R.
, Rennert H.
, Stanford J.L.
, Ostrander E.A.
, Chanock S.
, Wang M.H.
, Mittal R.D.
, et al.
.
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2011-03-01 00:00:00.0; 17(5), p. 1075-81.
EPub date: 2011-03-01 00:00:00.0.
PMID: 21343373
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Validation of genome-wide prostate cancer associations in men of African descent.
Authors: Chang B.L.
, Spangler E.
, Gallagher S.
, Haiman C.A.
, Henderson B.
, Isaacs W.
, Benford M.L.
, Kidd L.R.
, Cooney K.
, Strom S.
, et al.
.
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2011 Jan; 20(1), p. 23-32.
PMID: 21071540
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Promoter hypermethylation in prostate cancer.
Authors: Park J.Y.
.
Source: Cancer Control : Journal Of The Moffitt Cancer Center, 2010 Oct; 17(4), p. 245-55.
PMID: 20861812
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Identification of seven new prostate cancer susceptibility loci through a genome-wide association study.
Authors: Eeles R.A.
, Kote-Jarai Z.
, Al Olama A.A.
, Giles G.G.
, Guy M.
, Severi G.
, Muir K.
, Hopper J.L.
, Henderson B.E.
, Haiman C.A.
, et al.
.
Source: Nature Genetics, 2009 Oct; 41(10), p. 1116-21.
PMID: 19767753
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Single nucleotide polymorphisms in DNA repair genes and prostate cancer risk.
Authors: Park J.Y.
, Huang Y.
, Sellers T.A.
.
Source: Methods In Molecular Biology (clifton, N.j.), 2009; 471, p. 361-85.
PMID: 19109789
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