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Grant Details

Grant Number: 5R01CA067044-10 Interpret this number
Primary Investigator: Whittemore, Alice
Organization: Stanford University
Project Title: Genetic Epidemiology of Prostate Cancer
Fiscal Year: 2008
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Abstract

We have obtained pedigree data, blood and archived tissue from members of 98 families containing three or more confirmed cases of prostate cancer. We have typed these families for 437 autosomal markers and have analyzed the data for linkage. Although no single chromosomal region met the genome-wide criteria for statistically significant excess allele sharing, our strongest signal on the distal end of chromosome 19p has been replicated independently by a study of multiple-case prostate cancer families in Sweden (Wiklund et al. 2003). In this competing renewal application we request funds to test the hypothesis that region 19p13.3 harbors a prostate cancer susceptibility gene. Our objectives are to: 1) narrow the region by tripling the number of markers and perform linkage analysis to exclude subregions with low lod scores, using statistical methods that accommodate both individual-specific and family-specific covariates that may account for genetic heterogeneity across families; 2a) rank the 92 known genes and 61 transcripts of unknown genes in the (narrowed) region with respect to their potential involvement in prostate cancer, and 2b) identify polymorphisms in the more promising genes; 3a) investigate associations between prostate cancer risk and the variant alleles in the identified polymorphisms by genotyping 750 African-American and 750 Caucasian case-control pairs in a casecontrol study nested within the Hawaii/Los Angeles multiethnic cohort (MEC); 3b) when warranted, investigate the functional significance of these variants. The NCI-funded International Consortium for Prostate Cancer Genetics (ICPCG) is a resource of more than 1,500 multiple-case prostate cancer families. As members of the ICPCG, our long-term aim is to pursue with this group any promising leads identified in this project.

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Publications

Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families.
Authors: Bailey-Wilson JE, Childs EJ, Cropp CD, Schaid DJ, Xu J, Camp NJ, Cannon-Albright LA, Farnham JM, George A, Powell I, Carpten JD, Giles GG, Hopper JL, Severi G, English DR, Foulkes WD, Mæhle L, Møller P, Eeles R, Easton D, Guy M, Edwards S, Badzioch MD, Whittemore AS, Oakley-Girvan I, Hsieh CL, Dimitrov L, Stanford JL, Karyadi DM, Deutsch K, McIntosh L, Ostrander EA, Wiley KE, Isaacs SD, Walsh PC, Thibodeau SN, McDonnell SK, Hebbring S, Lange EM, Cooney KA, Tammela TL, Schleutker J, Maier C, Bochum S, Hoegel J, Grönberg H, Wiklund F, Emanuelsson M, Cancel-Tassin G, Valeri A, Cussenot O, Isaacs WB, International Consortium for Prostate Cancer Genetics
Source: BMC Med Genet, 2012 Jun 19;13, p. 46.
EPub date: 2012 Jun 19.
PMID: 22712434
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Chromosomes 4 and 8 implicated in a genome wide SNP linkage scan of 762 prostate cancer families collected by the ICPCG.
Authors: Lu L, Cancel-Tassin G, Valeri A, Cussenot O, Lange EM, Cooney KA, Farnham JM, Camp NJ, Cannon-Albright LA, Tammela TL, Schleutker J, Hoegel J, Herkommer K, Maier C, Vogel W, Wiklund F, Emanuelsson M, Grönberg H, Wiley KE, Isaacs SD, Walsh PC, Helfand BT, Kan D, Catalona WJ, Stanford JL, FitzGerald LM, Johanneson B, Deutsch K, McIntosh L, Ostrander EA, Thibodeau SN, McDonnell SK, Hebbring S, Schaid DJ, Whittemore AS, Oakley-Girvan I, Hsieh CL, Powell I, Bailey-Wilson JE, Cropp CD, Simpson C, Carpten JD, Seminara D, Zheng SL, Xu J, Giles GG, Severi G, Hopper JL, English DR, Foulkes WD, Maehle L, Moller P, Badzioch MD, Edwards S, Guy M, Eeles R, Easton D, Isaacs WB, International Consortium for Prostate Cancer Genetics
Source: Prostate, 2012 Mar;72(4), p. 410-26.
EPub date: 2011 Jul 11.
PMID: 21748754
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Multiple regions within 8q24 independently affect risk for prostate cancer.
Authors: Haiman CA, Patterson N, Freedman ML, Myers SR, Pike MC, Waliszewska A, Neubauer J, Tandon A, Schirmer C, McDonald GJ, Greenway SC, Stram DO, Le Marchand L, Kolonel LN, Frasco M, Wong D, Pooler LC, Ardlie K, Oakley-Girvan I, Whittemore AS, Cooney KA, John EM, Ingles SA, Altshuler D, Henderson BE, Reich D
Source: Nat Genet, 2007 May;39(5), p. 638-44.
EPub date: 2007 Apr 1.
PMID: 17401364
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Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men.
Authors: Freedman ML, Haiman CA, Patterson N, McDonald GJ, Tandon A, Waliszewska A, Penney K, Steen RG, Ardlie K, John EM, Oakley-Girvan I, Whittemore AS, Cooney KA, Ingles SA, Altshuler D, Henderson BE, Reich D
Source: Proc Natl Acad Sci U S A, 2006 Sep 19;103(38), p. 14068-73.
EPub date: 2006 Aug 31.
PMID: 16945910
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Pooled genome linkage scan of aggressive prostate cancer: results from the International Consortium for Prostate Cancer Genetics.
Authors: Schaid DJ, McDonnell SK, Zarfas KE, Cunningham JM, Hebbring S, Thibodeau SN, Eeles RA, Easton DF, Foulkes WD, Simard J, Giles GG, Hopper JL, Mahle L, Moller P, Badzioch M, Bishop DT, Evans C, Edwards S, Meitz J, Bullock S, Hope Q, Guy M, Hsieh CL, Halpern J, Balise RR, Oakley-Girvan I, Whittemore AS, Xu J, Dimitrov L, Chang BL, Adams TS, Turner AR, Meyers DA, Friedrichsen DM, Deutsch K, Kolb S, Janer M, Hood L, Ostrander EA, Stanford JL, Ewing CM, Gielzak M, Isaacs SD, Walsh PC, Wiley KE, Isaacs WB, Lange EM, Ho LA, Beebe-Dimmer JL, Wood DP, Cooney KA, Seminara D, Ikonen T, Baffoe-Bonnie A, Fredriksson H, Matikainen MP, Tammela TL, Bailey-Wilson J, Schleutker J, Maier C, Herkommer K, Hoegel JJ, Vogel W, Paiss T, Wiklund F, Emanuelsson M, Stenman E, Jonsson BA, Grönberg H, Camp NJ, Farnham J, Cannon-Albright LA, Catalona WJ, Suarez BK, Roehl KA
Source: Hum Genet, 2006 Nov;120(4), p. 471-85.
EPub date: 2006 Aug 25.
PMID: 16932970
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A combined genomewide linkage scan of 1,233 families for prostate cancer-susceptibility genes conducted by the international consortium for prostate cancer genetics.
Authors: Xu J, Dimitrov L, Chang BL, Adams TS, Turner AR, Meyers DA, Eeles RA, Easton DF, Foulkes WD, Simard J, Giles GG, Hopper JL, Mahle L, Moller P, Bishop T, Evans C, Edwards S, Meitz J, Bullock S, Hope Q, Hsieh CL, Halpern J, Balise RN, Oakley-Girvan I, Whittemore AS, Ewing CM, Gielzak M, Isaacs SD, Walsh PC, Wiley KE, Isaacs WB, Thibodeau SN, McDonnell SK, Cunningham JM, Zarfas KE, Hebbring S, Schaid DJ, Friedrichsen DM, Deutsch K, Kolb S, Badzioch M, Jarvik GP, Janer M, Hood L, Ostrander EA, Stanford JL, Lange EM, Beebe-Dimmer JL, Mohai CE, Cooney KA, Ikonen T, Baffoe-Bonnie A, Fredriksson H, Matikainen MP, Tammela TLj, Bailey-Wilson J, Schleutker J, Maier C, Herkommer K, Hoegel JJ, Vogel W, Paiss T, Wiklund F, Emanuelsson M, Stenman E, Jonsson BA, Gronberg H, Camp NJ, Farnham J, Cannon-Albright LA, Seminara D, ACTANE Consortium
Source: Am J Hum Genet, 2005 Aug;77(2), p. 219-29.
EPub date: 2005 Jun 29.
PMID: 15988677
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No evidence of linkage for chromosome 1q42.2-43 in prostate cancer.
Authors: Whittemore AS, Lin IG, Oakley-Girvan I, Gallagher RP, Halpern J, Kolonel LN, Wu AH, Hsieh CL
Source: Am J Hum Genet, 1999 Jul;65(1), p. 254-6.
PMID: 10364541
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