|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|
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.
Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A.
Authors: Wang H, Burnett T, Kono S, Haiman CA, Iwasaki M, Wilkens LR, Loo LW, Van Den Berg D, Kolonel LN, Henderson BE, Keku TO, Sandler RS, Signorello LB, Blot WJ, Newcomb PA, Pande M, Amos CI, West DW, Bézieau S, Berndt SI, Zanke BW, Hsu L, Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), Lindor NM, Haile RW, Hopper JL, Jenkins MA, Gallinger S, Casey G, Colon Cancer Family Registry (CCFR), Stenzel SL, Schumacher FR, Peters U, Gruber SB, Colorectal Transdisciplinary Study (CORECT), Tsugane S, Stram DO, Le Marchand L
Source: Nat Commun, 2014 Aug 8;5, p. 4613.
EPub date: 2014 Aug 8.
Generalizability of established prostate cancer risk variants in men of African ancestry.
Authors: Han Y, Signorello LB, Strom SS, Kittles RA, Rybicki BA, Stanford JL, Goodman PJ, Berndt SI, Carpten J, Casey G, Chu L, Conti DV, Rand KA, Diver WR, Hennis AJ, John EM, Kibel AS, Klein EA, Kolb S, Marchand LL, Leske MC, Murphy AB, Neslund-Dudas C, Park JY, Pettaway C, Rebbeck TR, Gapstur SM, Zheng SL, Wu SY, Witte JS, Xu J, Isaacs W, Ingles SA, Hsing A, The PRACTICAL Consortium, The ELLIPSE GAME-ON Consortium, Easton DF, Eeles RA, Schumacher FR, Chanock S, Nemesure B, Blot WJ, Stram DO, Henderson BE, Haiman CA
Source: Int J Cancer, 2014 Jul 8;null, p. null.
EPub date: 2014 Jul 8.
Variants at IRX4 as prostate cancer expression quantitative trait loci.
Authors: Xu X, Hussain WM, Vijai J, Offit K, Rubin MA, Demichelis F, Klein RJ
Source: Eur J Hum Genet, 2014 Apr;22(4), p. 558-63.
EPub date: 2013 Sep 11.
Genome-wide association of body fat distribution in African ancestry populations suggests new loci.
Authors: Liu CT, Monda KL, Taylor KC, Lange L, Demerath EW, Palmas W, Wojczynski MK, Ellis JC, Vitolins MZ, Liu S, Papanicolaou GJ, Irvin MR, Xue L, Griffin PJ, Nalls MA, Adeyemo A, Liu J, Li G, Ruiz-Narvaez EA, Chen WM, Chen F, Henderson BE, Millikan RC, Ambrosone CB, Strom SS, Guo X, Andrews JS, Sun YV, Mosley TH, Yanek LR, Shriner D, Haritunians T, Rotter JI, Speliotes EK, Smith M, Rosenberg L, Mychaleckyj J, Nayak U, Spruill I, Garvey WT, Pettaway C, Nyante S, Bandera EV, Britton AF, Zonderman AB, Rasmussen-Torvik LJ, Chen YD, Ding J, Lohman K, Kritchevsky SB, Zhao W, Peyser PA, Kardia SL, Kabagambe E, Broeckel U, Chen G, Zhou J, Wassertheil-Smoller S, Neuhouser ML, Rampersaud E, Psaty B, Kooperberg C, Manson JE, Kuller LH, Ochs-Balcom HM, Johnson KC, Sucheston L, Ordovas JM, Palmer JR, Haiman CA, McKnight B, Howard BV, Becker DM, Bielak LF, Liu Y, Allison MA, Grant SF, Burke GL, Patel SR, Schreiner PJ, Borecki IB, Evans MK, Taylor H, Sale MM, Howard V, Carlson CS, Rotimi CN, Cushman M, Harris TB, Reiner AP, Cupples LA, North KE, Fox CS
Source: PLoS Genet, 2013;9(8), p. e1003681.
EPub date: 2013 Aug 15.
A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry.
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Source: Nat Genet, 2013 Jun;45(6), p. 690-6.
EPub date: 2013 Apr 14.
Genome-wide testing of putative functional exonic variants in relationship with breast and prostate cancer risk in a multiethnic population.
Authors: Haiman CA, Han Y, Feng Y, Xia L, Hsu C, Sheng X, Pooler LC, Patel Y, Kolonel LN, Carter E, Park K, Le Marchand L, Van Den Berg D, Henderson BE, Stram DO
Source: PLoS Genet, 2013 Mar;9(3), p. e1003419.
EPub date: 2013 Mar 28.
Fine-mapping of IL16 gene and prostate cancer risk in African Americans.
Authors: Batai K, Shah E, Murphy AB, Newsome J, Ruden M, Ahaghotu C, Kittles RA
Source: Cancer Epidemiol Biomarkers Prev, 2012 Nov;21(11), p. 2059-68.
EPub date: 2012 Aug 24.
Detectable clonal mosaicism from birth to old age and its relationship to cancer.
Authors: Laurie CC, Laurie CA, Rice K, Doheny KF, Zelnick LR, McHugh CP, Ling H, Hetrick KN, Pugh EW, Amos C, Wei Q, Wang LE, Lee JE, Barnes KC, Hansel NN, Mathias R, Daley D, Beaty TH, Scott AF, Ruczinski I, Scharpf RB, Bierut LJ, Hartz SM, Landi MT, Freedman ND, Goldin LR, Ginsburg D, Li J, Desch KC, Strom SS, Blot WJ, Signorello LB, Ingles SA, Chanock SJ, Berndt SI, Le Marchand L, Henderson BE, Monroe KR, Heit JA, de Andrade M, Armasu SM, Regnier C, Lowe WL, Hayes MG, Marazita ML, Feingold E, Murray JC, Melbye M, Feenstra B, Kang JH, Wiggs JL, Jarvik GP, McDavid AN, Seshan VE, Mirel DB, Crenshaw A, Sharopova N, Wise A, Shen J, Crosslin DR, Levine DM, Zheng X, Udren JI, Bennett S, Nelson SC, Gogarten SM, Conomos MP, Heagerty P, Manolio T, Pasquale LR, Haiman CA, Caporaso N, Weir BS
Source: Nat Genet, 2012 May 6;44(6), p. 642-50.
EPub date: 2012 May 6.
Identification, replication, and fine-mapping of Loci associated with adult height in individuals of african ancestry.
Authors: N'Diaye A, Chen GK, Palmer CD, Ge B, Tayo B, Mathias RA, Ding J, Nalls MA, Adeyemo A, Adoue V, Ambrosone CB, Atwood L, Bandera EV, Becker LC, Berndt SI, Bernstein L, Blot WJ, Boerwinkle E, Britton A, Casey G, Chanock SJ, Demerath E, Deming SL, Diver WR, Fox C, Harris TB, Hernandez DG, Hu JJ, Ingles SA, John EM, Johnson C, Keating B, Kittles RA, Kolonel LN, Kritchevsky SB, Le Marchand L, Lohman K, Liu J, Millikan RC, Murphy A, Musani S, Neslund-Dudas C, North KE, Nyante S, Ogunniyi A, Ostrander EA, Papanicolaou G, Patel S, Pettaway CA, Press MF, Redline S, Rodriguez-Gil JL, Rotimi C, Rybicki BA, Salako B, Schreiner PJ, Signorello LB, Singleton AB, Stanford JL, Stram AH, Stram DO, Strom SS, Suktitipat B, Thun MJ, Witte JS, Yanek LR, Ziegler RG, Zheng W, Zhu X, Zmuda JM, Zonderman AB, Evans MK, Liu Y, Becker DM, Cooper RS, Pastinen T, Henderson BE, Hirschhorn JN, Lettre G, Haiman CA
Source: PLoS Genet, 2011 Oct;7(10), p. e1002298.
EPub date: 2011 Oct 6.
The landscape of recombination in African Americans.
Authors: Hinch AG, Tandon A, Patterson N, Song Y, Rohland N, Palmer CD, Chen GK, Wang K, Buxbaum SG, Akylbekova EL, Aldrich MC, Ambrosone CB, Amos C, Bandera EV, Berndt SI, Bernstein L, Blot WJ, Bock CH, Boerwinkle E, Cai Q, Caporaso N, Casey G, Cupples LA, Deming SL, Diver WR, Divers J, Fornage M, Gillanders EM, Glessner J, Harris CC, Hu JJ, Ingles SA, Isaacs W, John EM, Kao WH, Keating B, Kittles RA, Kolonel LN, Larkin E, Le Marchand L, McNeill LH, Millikan RC, Murphy A, Musani S, Neslund-Dudas C, Nyante S, Papanicolaou GJ, Press MF, Psaty BM, Reiner AP, Rich SS, Rodriguez-Gil JL, Rotter JI, Rybicki BA, Schwartz AG, Signorello LB, Spitz M, Strom SS, Thun MJ, Tucker MA, Wang Z, Wiencke JK, Witte JS, Wrensch M, Wu X, Yamamura Y, Zanetti KA, Zheng W, Ziegler RG, Zhu X, Redline S, Hirschhorn JN, Henderson BE, Taylor HA Jr, Price AL, Hakonarson H, Chanock SJ, Haiman CA, Wilson JG, Reich D, Myers SR
Source: Nature, 2011 Jul 20;476(7359), p. 170-5.
EPub date: 2011 Jul 20.
Characterizing genetic risk at known prostate cancer susceptibility loci in African Americans.
Authors: Haiman CA, Chen GK, Blot WJ, Strom SS, Berndt SI, Kittles RA, Rybicki BA, Isaacs WB, Ingles SA, Stanford JL, Diver WR, Witte JS, Chanock SJ, Kolb S, Signorello LB, Yamamura Y, Neslund-Dudas C, Thun MJ, Murphy A, Casey G, Sheng X, Wan P, Pooler LC, Monroe KR, Waters KM, Le Marchand L, Kolonel LN, Stram DO, Henderson BE
Source: PLoS Genet, 2011 May;7(5), p. e1001387.
EPub date: 2011 May 26.
Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21.
Authors: Haiman CA, Chen GK, Blot WJ, Strom SS, Berndt SI, Kittles RA, Rybicki BA, Isaacs WB, Ingles SA, Stanford JL, Diver WR, Witte JS, Hsing AW, Nemesure B, Rebbeck TR, Cooney KA, Xu J, Kibel AS, Hu JJ, John EM, Gueye SM, Watya S, Signorello LB, Hayes RB, Wang Z, Yeboah E, Tettey Y, Cai Q, Kolb S, Ostrander EA, Zeigler-Johnson C, Yamamura Y, Neslund-Dudas C, Haslag-Minoff J, Wu W, Thomas V, Allen GO, Murphy A, Chang BL, Zheng SL, Leske MC, Wu SY, Ray AM, Hennis AJ, Thun MJ, Carpten J, Casey G, Carter EN, Duarte ER, Xia LY, Sheng X, Wan P, Pooler LC, Cheng I, Monroe KR, Schumacher F, Le Marchand L, Kolonel LN, Chanock SJ, Van Den Berg D, Stram DO, Henderson BE
Source: Nat Genet, 2011 Jun;43(6), p. 570-3.
EPub date: 2011 May 22.
Tollip, a negative regulator of TLR-signalling, is encoded by twin genes in salmonid fish.
Authors: Rebl A, Hřyheim B, Fischer U, Köllner B, Siegl E, Seyfert HM
Source: Fish Shellfish Immunol, 2008 Jul;25(1-2), p. 153-62.
EPub date: 2008 Apr 13.