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Grant Details

Grant Number: 5RC2CA148085-02 Interpret this number
Primary Investigator: Haiman, Christopher
Organization: University Of Southern California
Project Title: Expanding Resources for Understanding the Genetic Basis for Prostate Cancer in Af
Fiscal Year: 2010


Abstract

DESCRIPTION (Provided by the applicant): Prostate cancer is one of the leading causes of morbidity and mortality among men. At the moment, we do not understand the underlying etiology, or why different groups, such as African Americans, have higher rates of disease. Risk factors for prostate cancer have remained elusive and aside from age, having a family history of the disease or African ancestry, until recently, no genetic or non-genetic (i.e., lifestyle) risk factors have been consistently demonstrated to contribute to variation in disease risk in the population. In this application, we propose to undertake a large-scale collaborative effort to uncover genetic predictors of prostate cancer in African American men. For this effort, we have assembled a multi-institutional team of investigators with experience in prostate cancer research in minority populations who are eager and willing to pool resources, specimens and data from their established studies, and to work closely together towards a common goal. To identify genetic factors that contribute to prostate cancer risk in African American men we propose to conduct a well-powered multi-stage genome-wide association study. We currently have funding (U01-NCI) to genotype 1,000,000 single nucleotide polymorphisms (SNPs) in 2,500 African American prostate cancer cases and 2,500 controls. We now propose to expand the size of stage 1 to 4,086 cases and 4,145 controls. In stage 2 we will perform follow-up genotyping of 1,500 SNPs that demonstrate significant main effects and interactions with known risk variants for prostate cancer (e.g. 8q24) in an additional 1,044 African American cases and 1,083 controls. In this study we will also assess the pan-ethnic effects of the variants identified in the African American scan, by replication testing in 600 prostate cancer cases and 1,050 controls from West Africa. In this dataset, we will also examine interactions between associated variants, environmental factors (thereby better defining the role of these factors) and disease severity. We expect this work to significantly advance knowledge of the etiology of prostate cancer and racial/ethnic disparities in prostate cancer risk, and to guide the development of future preventive, early detection, prognostic and even therapeutic measures. PUBLIC HEALTH RELEVANCE: The goal of this project is to identify common risk alleles for prostate cancer in African American men. For this effort, we have assembled a multi-institutional team of investigators with experience in prostate cancer research in minority populations who are eager and willing to pool resources, specimens and data from their established studies, and to work closely together towards a common goal. More specifically, we propose to conduct a multi-stage genome-wide association study of prostate cancer, which will include >5,500 African American cases and >5,100 African American male controls, to better define the subgroups of the African American population at greatest risk of developing this common cancer.



Publications

Novel colon cancer susceptibility variants identified from a genome-wide association study in African Americans.
Authors: Wang H. , Schmit S.L. , Haiman C.A. , Keku T.O. , Kato I. , Palmer J.R. , van den Berg D. , Wilkens L.R. , Burnett T. , Conti D.V. , et al. .
Source: International journal of cancer, 2017-06-15; 140(12), p. 2728-2733.
EPub date: 2017-03-28.
PMID: 28295283
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A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci.
Authors: Rand K.A. , Song C. , Dean E. , Serie D.J. , Curtin K. , Sheng X. , Hu D. , Huff C.A. , Bernal-Mizrachi L. , Tomasson M.H. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2016 12; 25(12), p. 1609-1618.
EPub date: 2016-09-01.
PMID: 27587788
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KAT2B polymorphism identified for drug abuse in African Americans with regulatory links to drug abuse pathways in human prefrontal cortex.
Authors: Johnson E.O. , Hancock D.B. , Levy J.L. , Gaddis N.C. , Page G.P. , Glasheen C. , Saccone N.L. , Bierut L.J. , Kral A.H. .
Source: Addiction biology, 2016 11; 21(6), p. 1217-1232.
EPub date: 2015-07-23.
PMID: 26202629
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Prostate Cancer Susceptibility in Men of African Ancestry at 8q24.
Authors: Han Y. , Rand K.A. , Hazelett D.J. , Ingles S.A. , Kittles R.A. , Strom S.S. , Rybicki B.A. , Nemesure B. , Isaacs W.B. , Stanford J.L. , et al. .
Source: Journal of the National Cancer Institute, 2016 Jul; 108(7), .
EPub date: 2016-01-27.
PMID: 26823525
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Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome.
Authors: Machiela M.J. , Zhou W. , Karlins E. , Sampson J.N. , Freedman N.D. , Yang Q. , Hicks B. , Dagnall C. , Hautman C. , Jacobs K.B. , et al. .
Source: Nature communications, 2016-06-13; 7, p. 11843.
EPub date: 2016-06-13.
PMID: 27291797
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Whole-exome sequencing of over 4100 men of African ancestry and prostate cancer risk.
Authors: Rand K.A. , Rohland N. , Tandon A. , Stram A. , Sheng X. , Do R. , Pasaniuc B. , Allen A. , Quinque D. , Mallick S. , et al. .
Source: Human molecular genetics, 2016-01-15; 25(2), p. 371-81.
EPub date: 2015-11-24.
PMID: 26604137
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The contribution of rare variation to prostate cancer heritability.
Authors: Mancuso N. , Rohland N. , Rand K.A. , Tandon A. , Allen A. , Quinque D. , Mallick S. , Li H. , Stram A. , Sheng X. , et al. .
Source: Nature genetics, 2016 Jan; 48(1), p. 30-5.
EPub date: 2015-11-16.
PMID: 26569126
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Replication of ZNF804A gene variant associations with risk of heroin addiction.
Authors: Hancock D.B. , Levy J.L. , Gaddis N.C. , Glasheen C. , Saccone N.L. , Page G.P. , Bierut L.J. , Kral A.H. , Johnson E.O. .
Source: Genes, brain, and behavior, 2015 Nov; 14(8), p. 635-40.
EPub date: 2015-10-20.
PMID: 26382569
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Integration of multiethnic fine-mapping and genomic annotation to prioritize candidate functional SNPs at prostate cancer susceptibility regions.
Authors: Han Y. , Hazelett D.J. , Wiklund F. , Schumacher F.R. , Stram D.O. , Berndt S.I. , Wang Z. , Rand K.A. , Hoover R.N. , Machiela M.J. , et al. .
Source: Human molecular genetics, 2015-10-01; 24(19), p. 5603-18.
EPub date: 2015-07-10.
PMID: 26162851
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Cis-Expression Quantitative Trait Loci Mapping Reveals Replicable Associations with Heroin Addiction in OPRM1.
Authors: Hancock D.B. , Levy J.L. , Gaddis N.C. , Glasheen C. , Saccone N.L. , Page G.P. , Hulse G.K. , Wildenauer D. , Kelty E.A. , Schwab S.G. , et al. .
Source: Biological psychiatry, 2015-10-01; 78(7), p. 474-84.
EPub date: 2015-01-29.
PMID: 25744370
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A large multiethnic genome-wide association study of prostate cancer identifies novel risk variants and substantial ethnic differences.
Authors: Hoffmann T.J. , Van Den Eeden S.K. , Sakoda L.C. , Jorgenson E. , Habel L.A. , Graff R.E. , Passarelli M.N. , Cario C.L. , Emami N.C. , Chao C.R. , et al. .
Source: Cancer discovery, 2015 Aug; 5(8), p. 878-91.
EPub date: 2015-06-01.
PMID: 26034056
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Generalizability of established prostate cancer risk variants in men of African ancestry.
Authors: Han Y. , Signorello L.B. , Strom S.S. , Kittles R.A. , Rybicki B.A. , Stanford J.L. , Goodman P.J. , Berndt S.I. , Carpten J. , Casey G. , et al. .
Source: International journal of cancer, 2015-03-01; 136(5), p. 1210-7.
EPub date: 2014-07-15.
PMID: 25044450
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Interaction between Red Meat Intake and NAT2 Genotype in Increasing the Risk of Colorectal Cancer in Japanese and African Americans.
Authors: Wang H. , Iwasaki M. , Haiman C.A. , Kono S. , Wilkens L.R. , Keku T.O. , Berndt S.I. , Tsugane S. , Le Marchand L. .
Source: PloS one, 2015; 10(12), p. e0144955.
EPub date: 2015-12-18.
PMID: 26683305
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Methodological Considerations in Estimation of Phenotype Heritability Using Genome-Wide SNP Data, Illustrated by an Analysis of the Heritability of Height in a Large Sample of African Ancestry Adults.
Authors: Chen F. , He J. , Zhang J. , Chen G.K. , Thomas V. , Ambrosone C.B. , Bandera E.V. , Berndt S.I. , Bernstein L. , Blot W.J. , et al. .
Source: PloS one, 2015; 10(6), p. e0131106.
EPub date: 2015-06-30.
PMID: 26125186
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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.
EPub date: 2014-09-14.
PMID: 25217961
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Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A.
Authors: Wang H. , Burnett T. , Kono S. , Haiman C.A. , Iwasaki M. , Wilkens L.R. , Loo L.W. , Van Den Berg D. , Kolonel L.N. , Henderson B.E. , et al. .
Source: Nature communications, 2014-08-08; 5, p. 4613.
EPub date: 2014-08-08.
PMID: 25105248
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Variants at IRX4 as prostate cancer expression quantitative trait loci.
Authors: Xu X. , Hussain W.M. , Vijai J. , Offit K. , Rubin M.A. , Demichelis F. , Klein R.J. .
Source: European journal of human genetics : EJHG, 2014 Apr; 22(4), p. 558-63.
EPub date: 2013-09-11.
PMID: 24022300
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A prostate cancer model build by a novel SVM-ID3 hybrid feature selection method using both genotyping and phenotype data from dbGaP.
Authors: Yücebaş S.C. , Aydın Son Y. .
Source: PloS one, 2014; 9(3), p. e91404.
EPub date: 2014-03-20.
PMID: 24651484
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A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry.
Authors: Monda K.L. , Chen G.K. , Taylor K.C. , Palmer C. , Edwards T.L. , Lange L.A. , Ng M.C. , Adeyemo A.A. , Allison M.A. , Bielak L.F. , et al. .
Source: Nature genetics, 2013 Jun; 45(6), p. 690-6.
EPub date: 2013-04-14.
PMID: 23583978
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Genome-wide testing of putative functional exonic variants in relationship with breast and prostate cancer risk in a multiethnic population.
Authors: Haiman C.A. , Han Y. , Feng Y. , Xia L. , Hsu C. , Sheng X. , Pooler L.C. , Patel Y. , Kolonel L.N. , Carter E. , et al. .
Source: PLoS genetics, 2013 Mar; 9(3), p. e1003419.
EPub date: 2013-03-28.
PMID: 23555315
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Genome-wide association of body fat distribution in African ancestry populations suggests new loci.
Authors: Liu C.T. , Monda K.L. , Taylor K.C. , Lange L. , Demerath E.W. , Palmas W. , Wojczynski M.K. , Ellis J.C. , Vitolins M.Z. , Liu S. , et al. .
Source: PLoS genetics, 2013; 9(8), p. e1003681.
EPub date: 2013-08-15.
PMID: 23966867
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Fine-mapping of IL16 gene and prostate cancer risk in African Americans.
Authors: Batai K. , Shah E. , Murphy A.B. , Newsome J. , Ruden M. , Ahaghotu C. , Kittles R.A. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2012 Nov; 21(11), p. 2059-68.
EPub date: 2012-08-24.
PMID: 22923025
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Detectable clonal mosaicism from birth to old age and its relationship to cancer.
Authors: Laurie C.C. , Laurie C.A. , Rice K. , Doheny K.F. , Zelnick L.R. , McHugh C.P. , Ling H. , Hetrick K.N. , Pugh E.W. , Amos C. , et al. .
Source: Nature genetics, 2012-05-06; 44(6), p. 642-50.
EPub date: 2012-05-06.
PMID: 22561516
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Identification, replication, and fine-mapping of Loci associated with adult height in individuals of african ancestry.
Authors: N'Diaye A. , Chen G.K. , Palmer C.D. , Ge B. , Tayo B. , Mathias R.A. , Ding J. , Nalls M.A. , Adeyemo A. , Adoue V. , et al. .
Source: PLoS genetics, 2011 Oct; 7(10), p. e1002298.
EPub date: 2011-10-06.
PMID: 21998595
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The landscape of recombination in African Americans.
Authors: Hinch A.G. , Tandon A. , Patterson N. , Song Y. , Rohland N. , Palmer C.D. , Chen G.K. , Wang K. , Buxbaum S.G. , Akylbekova E.L. , et al. .
Source: Nature, 2011-07-20; 476(7359), p. 170-5.
EPub date: 2011-07-20.
PMID: 21775986
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Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21.
Authors: Haiman C.A. , Chen G.K. , Blot W.J. , Strom S.S. , Berndt S.I. , Kittles R.A. , Rybicki B.A. , Isaacs W.B. , Ingles S.A. , Stanford J.L. , et al. .
Source: Nature genetics, 2011 Jun; 43(6), p. 570-3.
EPub date: 2011-05-22.
PMID: 21602798
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Characterizing genetic risk at known prostate cancer susceptibility loci in African Americans.
Authors: Haiman C.A. , Chen G.K. , Blot W.J. , Strom S.S. , Berndt S.I. , Kittles R.A. , Rybicki B.A. , Isaacs W.B. , Ingles S.A. , Stanford J.L. , et al. .
Source: PLoS genetics, 2011 May; 7(5), p. e1001387.
EPub date: 2011-05-26.
PMID: 21637779
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