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Grant Details

Grant Number: 5R01CA129684-04 Interpret this number
Primary Investigator: Xu, Jianfeng
Organization: Wake Forest University Health Sciences
Project Title: Confirmation of Snps Associated with Aggressive PCA in a GWA Study
Fiscal Year: 2011
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Abstract

DESCRIPTION (provided by applicant): Title: Confirmation of SNPs Associated with Aggressive PCa in a GWA study A genetic predisposition to prostate cancer (PCa) is well established and is the strongest among all common cancers. Inherited sequence variants in a number of genes, each conferring a moderate risk, are believed to collectively underlie the genetic predisposition. To systematically identify these risk variants, we have initiated an ambitious genome-wide association (GWA) study that includes several large and well characterized study populations in Sweden and Johns Hopkins Hospital, totaling > 10,000 cases and controls. Thus far, we have completed the 1st stage of this proposed GWA by studying 550K SNPs, including 20K nonsynonymous SNPs, among 500 aggressive cases and 500 controls from a Swedish population (CAPS). To further improve the power of identifying moderate risk SNPs, we propose a study to considerably increase the sample size for a GWA and systematically follow-up a large number of SNPs among independent study populations. We propose four specific aims to test the hypothesis that inherited sequence variants in the genome may increase or modify PCa risk. Aim 1) As the 2nd stage, we will genotype 500K SNPs and a subset of 50K supplement SNPs among an additional 800 aggressive PCa cases and 800 controls from Sweden. A joint association analysis among subjects in stages 1 & 2 will be performed to select SNPs for further confirmation. Aim 2) As the 3rd stage, we will test for PCa associations for the ~6,500 SNPs among an additional 2,000 aggressive PCa cases and 1,000 controls from Johns Hopkins Hospital. A combined analysis will be performed for these SNPs among all available subjects to identify SNPs that reach genome-wide significance level. Aim 3) Perform a fine mapping analysis at genomic regions surrounding the genome-wide significant SNPs to identify variants that are most strongly associated with PCa risk among all 3,300 aggressive PCa cases and 2,300 controls. Aim 4) Assess association of the PCa risk variants with the disease progression among 5,000 cases with extensive follow-up information from a Swedish Nationwide Follow-Up study of Localized PCa (FU-study) and 500 matched-pairs of progressors and non-progressors from Johns Hopkins Hospital. The identification of PCa risk variants may impact the understanding, prevention, diagnosis, and treatment of this disease.

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Publications

The Xu's chart for prostate biopsy: a visual presentation of the added value of biomarkers to prostate-specific antigen for estimating detection rates of prostate cancer.
Authors: Xu J
Source: Asian J Androl, 2014 Jul-Aug;16(4), p. 536-40.
PMID: 24625885
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Evaluation of reported prostate cancer risk-associated SNPs from genome-wide association studies of various racial populations in Chinese men.
Authors: Na R, Liu F, Zhang P, Ye D, Xu C, Shao Q, Qi J, Wang X, Chen Z, Wang M, He D, Wang Z, Zhou F, Yuan J, Gao X, Wei Q, Yang J, Jiao Y, Ou-Yang J, Zhu Y, Wu Q, Chen H, Lu D, Shi R, Lin X, Jiang H, Wang Z, Jiang D, Sun J, Zheng SL, Ding Q, Mo Z, Sun Y, Xu J
Source: Prostate, 2013 Nov;73(15), p. 1623-35.
EPub date: 2013 Sep 9.
PMID: 24038036
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Plateau effect of prostate cancer risk-associated SNPs in discriminating prostate biopsy outcomes.
Authors: Ren S, Xu J, Zhou T, Jiang H, Chen H, Liu F, Na R, Zhang L, Wu Y, Sun J, Yang B, Gao X, Zheng SL, Xu C, Ding Q, Sun Y
Source: Prostate, 2013 Dec;73(16), p. 1824-35.
EPub date: 2013 Aug 26.
PMID: 24037738
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Prediction of prostate cancer from prostate biopsy in Chinese men using a genetic score derived from 24 prostate cancer risk-associated SNPs.
Authors: Jiang H, Liu F, Wang Z, Na R, Zhang L, Wu Y, Zheng J, Lin X, Jiang D, Sun J, Zheng SL, Ding Q, Xu J
Source: Prostate, 2013 Nov;73(15), p. 1651-9.
EPub date: 2013 Jul 18.
PMID: 23868750
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HOXB13 is a susceptibility gene for prostate cancer: results from the International Consortium for Prostate Cancer Genetics (ICPCG).
Authors: Xu J, Lange EM, Lu L, Zheng SL, Wang Z, Thibodeau SN, Cannon-Albright LA, Teerlink CC, Camp NJ, Johnson AM, Zuhlke KA, Stanford JL, Ostrander EA, Wiley KE, Isaacs SD, Walsh PC, Maier C, Luedeke M, Vogel W, Schleutker J, Wahlfors T, Tammela T, Schaid D, McDonnell SK, DeRycke MS, Cancel-Tassin G, Cussenot O, Wiklund F, Grönberg H, Eeles R, Easton D, Kote-Jarai Z, Whittemore AS, Hsieh CL, Giles GG, Hopper JL, Severi G, Catalona WJ, Mandal D, Ledet E, Foulkes WD, Hamel N, Mahle L, Moller P, Powell I, Bailey-Wilson JE, Carpten JD, Seminara D, Cooney KA, Isaacs WB, International Consortium for Prostate Cancer Genetics
Source: Hum Genet, 2013 Jan;132(1), p. 5-14.
EPub date: 2012 Oct 12.
PMID: 23064873
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Genome-wide association study in Chinese men identifies two new prostate cancer risk loci at 9q31.2 and 19q13.4.
Authors: Xu J, Mo Z, Ye D, Wang M, Liu F, Jin G, Xu C, Wang X, Shao Q, Chen Z, Tao Z, Qi J, Zhou F, Wang Z, Fu Y, He D, Wei Q, Guo J, Wu D, Gao X, Yuan J, Wang G, Xu Y, Wang G, Yao H, Dong P, Jiao Y, Shen M, Yang J, Ou-Yang J, Jiang H, Zhu Y, Ren S, Zhang Z, Yin C, Gao X, Dai B, Hu Z, Yang Y, Wu Q, Chen H, Peng P, Zheng Y, Zheng X, Xiang Y, Long J, Gong J, Na R, Lin X, Yu H, Wang Z, Tao S, Feng J, Sun J, Liu W, Hsing A, Rao J, Ding Q, Wiklund F, Gronberg H, Shu XO, Zheng W, Shen H, Jin L, Shi R, Lu D, Zhang X, Sun J, Zheng SL, Sun Y
Source: Nat Genet, 2012 Nov;44(11), p. 1231-5.
EPub date: 2012 Sep 30.
PMID: 23023329
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A novel germline mutation in HOXB13 is associated with prostate cancer risk in Chinese men.
Authors: Lin X, Qu L, Chen Z, Xu C, Ye D, Shao Q, Wang X, Qi J, Chen Z, Zhou F, Wang M, Wang Z, He D, Wu D, Gao X, Yuan J, Wang G, Xu Y, Wang G, Dong P, Jiao Y, Yang J, Ou-Yang J, Jiang H, Zhu Y, Ren S, Zhang Z, Yin C, Wu Q, Zheng Y, Turner AR, Tao S, Na R, Ding Q, Lu D, Shi R, Sun J, Liu F, Zheng SL, Mo Z, Sun Y, Xu J
Source: Prostate, 2013 Jan;73(2), p. 169-75.
EPub date: 2012 Jun 21.
PMID: 22718278
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Using graded response model for the prediction of prostate cancer risk.
Authors: Chen SH, Ip EH, Xu J, Sun J, Hsu FC
Source: Hum Genet, 2012 Aug;131(8), p. 1327-36.
EPub date: 2012 Mar 30.
PMID: 22461065
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Genome-wide two-locus epistasis scans in prostate cancer using two European populations.
Authors: Tao S, Feng J, Webster T, Jin G, Hsu FC, Chen SH, Kim ST, Wang Z, Zhang Z, Zheng SL, Isaacs WB, Xu J, Sun J
Source: Hum Genet, 2012 Jul;131(7), p. 1225-34.
EPub date: 2012 Feb 26.
PMID: 22367438
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A genome-wide search for loci interacting with known prostate cancer risk-associated genetic variants.
Authors: Tao S, Wang Z, Feng J, Hsu FC, Jin G, Kim ST, Zhang Z, Gronberg H, Zheng LS, Isaacs WB, Xu J, Sun J
Source: Carcinogenesis, 2012 Mar;33(3), p. 598-603.
EPub date: 2012 Jan 4.
PMID: 22219177
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Validation of prostate cancer risk-related loci identified from genome-wide association studies using family-based association analysis: evidence from the International Consortium for Prostate Cancer Genetics (ICPCG).
Authors: Jin G, Lu L, Cooney KA, Ray AM, Zuhlke KA, Lange EM, Cannon-Albright LA, Camp NJ, Teerlink CC, Fitzgerald LM, Stanford JL, Wiley KE, Isaacs SD, Walsh PC, Foulkes WD, Giles GG, Hopper JL, Severi G, Eeles R, Easton D, Kote-Jarai Z, Guy M, Rinckleb A, Maier C, Vogel W, Cancel-Tassin G, Egrot C, Cussenot O, Thibodeau SN, McDonnell SK, Schaid DJ, Wiklund F, Grönberg H, Emanuelsson M, Whittemore AS, Oakley-Girvan I, Hsieh CL, Wahlfors T, Tammela T, Schleutker J, Catalona WJ, Zheng SL, Ostrander EA, Isaacs WB, Xu J, International Consortium for Prostate Cancer Genetics
Source: Hum Genet, 2012 Jul;131(7), p. 1095-103.
EPub date: 2011 Dec 25.
PMID: 22198737
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Replication and cumulative effects of GWAS-identified genetic variations for prostate cancer in Asians: a case-control study in the ChinaPCa consortium.
Authors: Wang M, Liu F, Hsing AW, Wang X, Shao Q, Qi J, Ye Y, Wang Z, Chen H, Gao X, Wang G, Chu LW, Ding Q, OuYang J, Gao X, Huang Y, Chen Y, Gao YT, Zhang ZF, Rao J, Shi R, Wu Q, Zhang Y, Jiang H, Zheng J, Hu Y, Guo L, Lin X, Tao S, Jin G, Sun J, Lu D, Zheng SL, Sun Y, Mo Z, Yin C, Zhang Z, Xu J
Source: Carcinogenesis, 2012 Feb;33(2), p. 356-60.
EPub date: 2011 Nov 23.
PMID: 22114074
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A genome-wide survey over the ChIP-on-chip identified androgen receptor-binding genomic regions identifies a novel prostate cancer susceptibility locus at 12q13.13.
Authors: Feng J, Sun J, Kim ST, Lu Y, Wang Z, Zhang Z, Gronberg H, Isaacs WB, Zheng SL, Xu J
Source: Cancer Epidemiol Biomarkers Prev, 2011 Nov;20(11), p. 2396-403.
EPub date: 2011 Sep 29.
PMID: 21960693
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Human polymorphisms at long non-coding RNAs (lncRNAs) and association with prostate cancer risk.
Authors: Jin G, Sun J, Isaacs SD, Wiley KE, Kim ST, Chu LW, Zhang Z, Zhao H, Zheng SL, Isaacs WB, Xu J
Source: Carcinogenesis, 2011 Nov;32(11), p. 1655-9.
EPub date: 2011 Aug 19.
PMID: 21856995
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Genetic variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes are prognostic markers of prostate cancer-specific mortality.
Authors: Lin DW, FitzGerald LM, Fu R, Kwon EM, Zheng SL, Kolb S, Wiklund F, Stattin P, Isaacs WB, Xu J, Ostrander EA, Feng Z, Grönberg H, Stanford JL
Source: Cancer Epidemiol Biomarkers Prev, 2011 Sep;20(9), p. 1928-36.
EPub date: 2011 Aug 16.
PMID: 21846818
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Predictive performance of prostate cancer risk in Chinese men using 33 reported prostate cancer risk-associated SNPs.
Authors: Zheng J, Liu F, Lin X, Wang X, Ding Q, Jiang H, Chen H, Lu D, Jin G, Hsing AW, Shao Q, Qi J, Ye Y, Wang Z, Gao X, Wang G, Chu LW, Ouyang J, Huang Y, Chen Y, Gao Y, Shi R, Wu Q, Wang M, Zhang Z, Hu Y, Sun J, Zheng SL, Gao X, Xu C, Mo Z, Sun Y, Xu J
Source: Prostate, 2012 Apr;72(5), p. 577-83.
EPub date: 2011 Jul 27.
PMID: 21796652
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Systematic confirmation study of reported prostate cancer risk-associated single nucleotide polymorphisms in Chinese men.
Authors: Liu F, Hsing AW, Wang X, Shao Q, Qi J, Ye Y, Wang Z, Chen H, Gao X, Wang G, Chu LW, Ding Q, OuYang J, Gao X, Huang Y, Chen Y, Gao YT, Zhang ZF, Rao J, Shi R, Wu Q, Wang M, Zhang Z, Zhang Y, Jiang H, Zheng J, Hu Y, Guo L, Lin X, Tao S, Jin G, Sun J, Lu D, Zheng SL, Sun Y, Mo Z, Xu J
Source: Cancer Sci, 2011 Oct;102(10), p. 1916-20.
EPub date: 2011 Aug 10.
PMID: 21756274
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Association of prostate cancer risk with SNPs in regions containing androgen receptor binding sites captured by ChIP-On-chip analyses.
Authors: Lu Y, Sun J, Kader AK, Kim ST, Kim JW, Liu W, Sun J, Lu D, Feng J, Zhu Y, Jin T, Zhang Z, Dimitrov L, Lowey J, Campbell K, Suh E, Duggan D, Carpten J, Trent JM, Gronberg H, Zheng SL, Isaacs WB, Xu J
Source: Prostate, 2012 Mar;72(4), p. 376-85.
EPub date: 2011 Jun 10.
PMID: 21671247
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Large-scale fine mapping of the HNF1B locus and prostate cancer risk.
Authors: Berndt SI, Sampson J, Yeager M, Jacobs KB, Wang Z, Hutchinson A, Chung C, Orr N, Wacholder S, Chatterjee N, Yu K, Kraft P, Feigelson HS, Thun MJ, Diver WR, Albanes D, Virtamo J, Weinstein S, Schumacher FR, Cancel-Tassin G, Cussenot O, Valeri A, Andriole GL, Crawford ED, Haiman C, Henderson B, Kolonel L, Le Marchand L, Siddiq A, Riboli E, Travis RC, Kaaks R, Isaacs W, Isaacs S, Wiley KE, Gronberg H, Wiklund F, Stattin P, Xu J, Zheng SL, Sun J, Vatten LJ, Hveem K, Njølstad I, Gerhard DS, Tucker M, Hayes RB, Hoover RN, Fraumeni JF Jr, Hunter DJ, Thomas G, Chanock SJ
Source: Hum Mol Genet, 2011 Aug 15;20(16), p. 3322-9.
EPub date: 2011 May 16.
PMID: 21576123
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