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National Institutes of Health: National Cancer Institute: Division of Cancer Control and Population Sciences
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

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 E.M. , Cooney K.A. , Farnham J.M. , Camp N.J. , Cannon-Albright L.A. , Tammela T.L. , et al. .
Source: The Prostate, 2012 Mar; 72(4), p. 410-26.
PMID: 21748754
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Analysis Of Xq27-28 Linkage In The International Consortium For Prostate Cancer Genetics (icpcg) Families
Authors: Bailey-Wilson J.E. , Childs E.J. , Cropp C.D. , Schaid D.J. , Xu J. , Camp N.J. , Cannon-Albright L.A. , Farnham J.M. , George A. , Powell I. , et al. .
Source: Bmc Medical Genetics, 2012; 13, p. 46.
PMID: 22712434
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Multiple Regions Within 8q24 Independently Affect Risk For Prostate Cancer
Authors: Haiman C.A. , Patterson N. , Freedman M.L. , Myers S.R. , Pike M.C. , Waliszewska A. , Neubauer J. , Tandon A. , Schirmer C. , McDonald G.J. , et al. .
Source: Nature Genetics, 2007 May; 39(5), p. 638-44.
PMID: 17401364
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Pooled Genome Linkage Scan Of Aggressive Prostate Cancer: Results From The International Consortium For Prostate Cancer Genetics
Authors: Schaid D.J. , McDonnell S.K. , Zarfas K.E. , Cunningham J.M. , Hebbring S. , Thibodeau S.N. , Eeles R.A. , Easton D.F. , Foulkes W.D. , Simard J. , et al. .
Source: Human Genetics, 2006 Nov; 120(4), p. 471-85.
PMID: 16932970
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Admixture Mapping Identifies 8q24 As A Prostate Cancer Risk Locus In African-american Men
Authors: Freedman M.L. , Haiman C.A. , Patterson N. , McDonald G.J. , Tandon A. , Waliszewska A. , Penney K. , Steen R.G. , Ardlie K. , John E.M. , et al. .
Source: Proceedings Of The National Academy Of Sciences Of The United States Of America, 2006-09-19 00:00:00.0; 103(38), p. 14068-73.
PMID: 16945910
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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 B.L. , Adams T.S. , Turner A.R. , Meyers D.A. , Eeles R.A. , Easton D.F. , Foulkes W.D. , Simard J. , et al. .
Source: American Journal Of Human Genetics, 2005 Aug; 77(2), p. 219-29.
PMID: 15988677
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No Evidence Of Linkage For Chromosome 1q42.2-43 In Prostate Cancer
Authors: Whittemore A.S. , Lin I.G. , Oakley-Girvan I. , Gallagher R.P. , Halpern J. , Kolonel L.N. , Wu A.H. , Hsieh C.L. .
Source: American Journal Of Human Genetics, 1999 Jul; 65(1), p. 254-6.
PMID: 10364541
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