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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29CA073270-03
Application #
2733323
Study Section
Special Emphasis Panel (ZRG7-STA (01))
Program Officer
Erickson, Burdette (BUD) W
Project Start
1996-07-01
Project End
2001-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Fijal, Bonnie A; Idury, Ramana M; Witte, John S (2002) Analysis of mutational spectra: locating hotspots and clusters of mutations using recursive segmentation. Stat Med 21:1867-85
Thomas, Duncan C; Witte, John S (2002) Point: population stratification: a problem for case-control studies of candidate-gene associations? Cancer Epidemiol Biomarkers Prev 11:505-12
Fijal, B A; Kim, L L; Buxbaum, S G et al. (2001) Predicting quantitative trait levels by modeling SNP interaction. Genet Epidemiol 21 Suppl 1:S608-13
Kim, L L; Fijal, B A; Witte, J S (2001) Hierarchical modeling of the relation between sequence variants and a quantitative trait: addressing multiple comparison and population stratification issues. Genet Epidemiol 21 Suppl 1:S668-73
Witte, J S; Elston, R C; Cardon, L R (2000) On the relative sample size required for multiple comparisons. Stat Med 19:369-72
Fijal, B A; Hall, J M; Witte, J S (2000) Clinical trials in the genomic era: effects of protective genotypes on sample size and duration of trial. Control Clin Trials 21:20-Jul
Witte, J S; Greenland, S; Kim, L L et al. (2000) Multilevel modeling in epidemiology with GLIMMIX. Epidemiology 11:684-8
Witte, J S; Goddard, K A; Conti, D V et al. (2000) Genomewide scan for prostate cancer-aggressiveness loci. Am J Hum Genet 67:92-9
Goddard, K A; Hopkins, P J; Hall, J M et al. (2000) Linkage disequilibrium and allele-frequency distributions for 114 single-nucleotide polymorphisms in five populations. Am J Hum Genet 66:216-34
Witte, J S; Carlin, J B; Hopper, J L (1999) Likelihood-based approach to estimating twin concordance for dichotomous traits. Genet Epidemiol 16:290-304

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