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Grant Details

Grant Number: 5R01CA078836-07 Interpret this number
Primary Investigator: Nelson, Peter
Organization: Fred Hutchinson Cancer Research Center
Project Title: Genetics of Prostate Cancer Susceptibility
Fiscal Year: 2005


DESCRIPTION (provided by applicant): Prostate cancer is the most common cancer and the second leading cause of cancer deaths among men in the U.S. Epidemiological data and segregation analyses support the hypothesis that genetic components contribute strongly to susceptibility, particularly in men diagnosed at younger ages or men with a family history of disease. We have conducted a genome-wide scan of 254 high-risk prostate cancer families collected, characterized, and genotyped largely in the past 3 years. We now propose to utilize the resulting data to identify putative susceptibility genes through the following aims. Initially, we will assign priorities for follow-up of provocative regions by refined mapping. Analyses derived from the entire data set as well as stratified subsets of families grouped by age at onset, family history, and clinical features of disease will be considered. Regions for which the most compelling and consistent data are observed using a set of stated criteria will be selected for detailed follow-up and verification. Once loci of interest are prioritized, we will define a minimum critical region for each by genotyping additional markers and identifying recombinants relative to markers and known genes. A physical map of BACs across regions of interest will be constructed using publicly available data, with gaps filled In by additional screening and sequencing as needed. Oligoarrays of exons across the minimum region will then be constructed and probed with mRNA isolated from both normal prostate and tumor to identify genes from the region of interest. Additional information will likely be derived from analysis of tumors from putatively linked families on the same oligoarrays. Final selection of candidate genes will be made using array data, functional information, and publicly available expression data. Full-length cDNA clones will be isolated and sequenced as needed. These genes, together with any identified by other investigators, will be fully analyzed for disease-associated mutations and polymorphisms, including SNPs, in the 254 family data set. The resulting data will provide information about the type and distribution of mutations in high-risk families as well as provide useful information for understanding genetic heterogeneity of prostate cancer.


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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.
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Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for Prostate Cancer Genetics using novel sumLINK and sumLOD analyses.
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Identification and characterization of novel SNPs in CHEK2 in Ashkenazi Jewish men with prostate cancer.
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Searching for epistasis and linkage heterogeneity by correlations of pedigree-specific linkage scores.
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Fine mapping of familial prostate cancer families narrows the interval for a susceptibility locus on chromosome 22q12.3 to 1.36 Mb.
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Genome-wide linkage scan of prostate cancer Gleason score and confirmation of chromosome 19q.
Authors: Schaid D.J. , Stanford J.L. , McDonnell S.K. , Suuriniemi M. , McIntosh L. , Karyadi D.M. , Carlson E.E. , Deutsch K. , Janer M. , Hood L. , et al. .
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Affected relative pairs and simultaneous search for two-locus linkage in the presence of epistasis.
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Compelling evidence for a prostate cancer gene at 22q12.3 by the International Consortium for Prostate Cancer Genetics.
Authors: Camp N.J. , Cannon-Albright L.A. , Farnham J.M. , Baffoe-Bonnie A.B. , George A. , Powell I. , Bailey-Wilson J.E. , Carpten J.D. , Giles G.G. , Hopper J.L. , et al. .
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Suggestive genetic linkage to chromosome 11p11.2-q12.2 in hereditary prostate cancer families with primary kidney cancer.
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PMID: 17372923
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Genetic background influences murine prostate gene expression: implications for cancer phenotypes.
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Genetic susceptibility to aggressive prostate cancer.
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Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2006 Oct; 15(10), p. 1761-4.
PMID: 17035380
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Prostate cancer and genetic susceptibility: a genome scan incorporating disease aggressiveness.
Authors: Stanford J.L. , McDonnell S.K. , Friedrichsen D.M. , Carlson E.E. , Kolb S. , Deutsch K. , Janer M. , Hood L. , Ostrander E.A. , Schaid D.J. .
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Met160Val polymorphism in the TRMPSS2 gene and risk of prostate cancer in a population-based case-control study.
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Identification of a prostate cancer susceptibility locus on chromosome 7q11-21 in Jewish families.
Authors: Friedrichsen D.M. , Stanford J.L. , Isaacs S.D. , Janer M. , Chang B.L. , Deutsch K. , Gillanders E. , Kolb S. , Wiley K.E. , Badzioch M.D. , et al. .
Source: Proceedings of the National Academy of Sciences of the United States of America, 2004-02-17; 101(7), p. 1939-44.
EPub date: 2004-02-09.
PMID: 14769943
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Genomic scan of 254 hereditary prostate cancer families.
Authors: Janer M. , Friedrichsen D.M. , Stanford J.L. , Badzioch M.D. , Kolb S. , Deutsch K. , Peters M.A. , Goode E.L. , Welti R. , DeFrance H.B. , et al. .
Source: The Prostate, 2003-12-01; 57(4), p. 309-19.
PMID: 14601027
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Oligogenic segregation analysis of hereditary prostate cancer pedigrees: evidence for multiple loci affecting age at onset.
Authors: Conlon E.M. , Goode E.L. , Gibbs M. , Stanford J.L. , Badzioch M. , Janer M. , Kolb S. , Hood L. , Ostrander E.A. , Jarvik G.P. , et al. .
Source: International journal of cancer, 2003-07-10; 105(5), p. 630-5.
PMID: 12740911
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Germline mutations in the p73 gene do not predispose to familial prostate-brain cancer.
Authors: Peters M.A. , Janer M. , Kolb S. , Jarvik G.P. , Ostrander E.A. , Stanford J.L. .
Source: The Prostate, 2001-09-15; 48(4), p. 292-6.
PMID: 11536309
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Clinical characteristics of prostate cancer in an analysis of linkage to four putative susceptibility loci.
Authors: Goode E.L. , Stanford J.L. , Peters M.A. , Janer M. , Gibbs M. , Kolb S. , Badzioch M.D. , Hood L. , Ostrander E.A. , Jarvik G.P. .
Source: Clinical cancer research : an official journal of the American Association for Cancer Research, 2001 Sep; 7(9), p. 2739-49.
PMID: 11555587
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Genetic linkage analysis of prostate cancer families to Xq27-28.
Authors: Peters M.A. , Jarvik G.P. , Janer M. , Chakrabarti L. , Kolb S. , Goode E.L. , Gibbs M. , DuBois C.C. , Schuster E.F. , Hood L. , et al. .
Source: Human heredity, 2001; 51(1-2), p. 107-13.
PMID: 11096277
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A genomic scan of families with prostate cancer identifies multiple regions of interest.
Authors: Gibbs M. , Stanford J.L. , Jarvik G.P. , Janer M. , Badzioch M. , Peters M.A. , Goode E.L. , Kolb S. , Chakrabarti L. , Shook M. , et al. .
Source: American journal of human genetics, 2000 Jul; 67(1), p. 100-9.
EPub date: 2000-05-19.
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