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Grant Details

Grant Number: 5R29CA073270-05 Interpret this number
Primary Investigator: Witte, John
Organization: Case Western Reserve University
Project Title: Hierarchical Modeling in Cancer Research
Fiscal Year: 2000
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Abstract

DESCRIPTION: Extensions of the methods of hierarchical modelling and analysis are proposed through application to data sets in four different areas of study: relationship of genetic mutations to breast and ovarian cancer; diet and the development of colorectal adenomatous polyps; exposure to low levels of ionizing radiation and cancer; and relationship between chemical exposures and cancer in humans and the same exposures and cancer in animal test species. In each case data sets are available to the investigator. The method depends on expressing the target parameters to be estimated as functions of more basic parameters so that these postulated relationships can be used to "incorporate similarities" among the target parameters so as to obtain "more plausible and stable estimates" of their effects. The extensions to the methods depend to some extent on the various data sets but include multistage modeling of the relationship between the target parameters and the more basic parameters, by grouping them or by adding a further level of them and by grouping the dependent binary variables where several of them are involved, e.g. different sites of disease. A variety of checks on sensitivity and performance is planned for each of the four areas of study, including checks on different choices of the parameters in the higher models and simulation of the results, using the basic data sets as guides to "true" structure.

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Publications

Analysis of mutational spectra: locating hotspots and clusters of mutations using recursive segmentation.
Authors: Fijal B.A. , Idury R.M. , Witte J.S. .
Source: Statistics in medicine, 2002-07-15; 21(13), p. 1867-85.
PMID: 12111894
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Point: population stratification: a problem for case-control studies of candidate-gene associations?
Authors: Thomas D.C. , Witte J.S. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2002 Jun; 11(6), p. 505-12.
PMID: 12050090
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Hierarchical modeling of the relation between sequence variants and a quantitative trait: addressing multiple comparison and population stratification issues.
Authors: Kim L.L. , Fijal B.A. , Witte J.S. .
Source: Genetic epidemiology, 2001; 21 Suppl 1, p. S668-73.
PMID: 11793759
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Predicting quantitative trait levels by modeling SNP interaction.
Authors: Fijal B.A. , Kim L.L. , Buxbaum S.G. , Witte J.S. .
Source: Genetic epidemiology, 2001; 21 Suppl 1, p. S608-13.
PMID: 11793747
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Multilevel modeling in epidemiology with GLIMMIX.
Authors: Witte J.S. , Greenland S. , Kim L.L. , Arab L. .
Source: Epidemiology (Cambridge, Mass.), 2000 Nov; 11(6), p. 684-8.
PMID: 11055630
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Genomewide scan for prostate cancer-aggressiveness loci.
Authors: Witte J.S. , Goddard K.A. , Conti D.V. , Elston R.C. , Lin J. , Suarez B.K. , Broman K.W. , Burmester J.K. , Weber J.L. , Catalona W.J. .
Source: American journal of human genetics, 2000 Jul; 67(1), p. 92-9.
EPub date: 2000-05-24.
PMID: 10825281
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On the relative sample size required for multiple comparisons.
Authors: Witte J.S. , Elston R.C. , Cardon L.R. .
Source: Statistics in medicine, 2000-02-15; 19(3), p. 369-72.
PMID: 10649302
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Clinical trials in the genomic era: effects of protective genotypes on sample size and duration of trial.
Authors: Fijal B.A. , Hall J.M. , Witte J.S. .
Source: Controlled clinical trials, 2000 Feb; 21(1), p. 7-20.
PMID: 10660000
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Linkage disequilibrium and allele-frequency distributions for 114 single-nucleotide polymorphisms in five populations.
Authors: Goddard K.A. , Hopkins P.J. , Hall J.M. , Witte J.S. .
Source: American journal of human genetics, 2000 Jan; 66(1), p. 216-34.
PMID: 10631153
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Genetic mapping of complex traits.
Authors: Olson J.M. , Witte J.S. , Elston R.C. .
Source: Statistics in medicine, 1999-11-15; 18(21), p. 2961-81.
PMID: 10523753
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Asymptotic bias and efficiency in case-control studies of candidate genes and gene-environment interactions: basic family designs.
Authors: Witte J.S. , Gauderman W.J. , Thomas D.C. .
Source: American journal of epidemiology, 1999-04-15; 149(8), p. 693-705.
PMID: 10206618
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Family-based association studies.
Authors: Gauderman W.J. , Witte J.S. , Thomas D.C. .
Source: Journal of the National Cancer Institute. Monographs, 1999; (26), p. 31-7.
PMID: 10854483
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Likelihood-based approach to estimating twin concordance for dichotomous traits.
Authors: Witte J.S. , Carlin J.B. , Hopper J.L. .
Source: Genetic epidemiology, 1999; 16(3), p. 290-304.
PMID: 10096691
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Software for hierarchical modeling of epidemiologic data.
Authors: Witte J.S. , Greenland S. , Kim L.L. .
Source: Epidemiology (Cambridge, Mass.), 1998 Sep; 9(5), p. 563-6.
PMID: 9730038
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Evaluating the performance of a genetic test using information from previous studies in place of a gold standard.
Authors: Fijal B.A. , Witte J.S. .
Source: Medical care, 1998 Aug; 36(8 Suppl), p. AS46-56.
PMID: 9708582
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A nested approach to evaluating dose-response and trend.
Authors: Witte J.S. , Greenland S. .
Source: Annals of epidemiology, 1997 Apr; 7(3), p. 188-93.
PMID: 9141641
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Genetic analysis with hierarchical models.
Authors: Witte J.S. .
Source: Genetic epidemiology, 1997; 14(6), p. 1137-42.
PMID: 9433637
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