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

Grant Number: 5R01CA094069-10 Interpret this number
Primary Investigator: Whittemore, Alice
Organization: Stanford University
Project Title: "Statistical Methods for Genetic Epidemiology"
Fiscal Year: 2011
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Abstract

DESCRIPTION (provided by applicant): The availability of high-dimensional single-nucleotide (SNP) data for large samples of individuals with and without disease presents unprecedented opportunities for genetic epidemiologists, but also many statistical challenges. Our ability to bring these opportunities to fruition depends on the development and application of sound and innovative statistical methods. Areas of particularly great need include methods for dealing with multiple hypothesis-testing problems (multiple comparison issues), and methods for combining data from multiple sources to achieve sharper inferences (data synthesis issues). The goals of this research are to develop new or improved methods for addressing these issues, and to apply them to data on cancers of the breast, ovary and prostate. To accomplish these goals, the investigators will build on more than 15 years of previous work. Specifically, in 1988 the National Cancer Institute (NCI) awarded an Outstanding Investigator Grant (OIG) to the Principle Investigator for the development and application of new and improved statistical methods for use in epidemiological research. In 1995 this grant was renewed until NCI terminated the program in 2001. The research was then funded by R01 CA94069 for the period January 2002 to December 2006. This competing renewal application requests funds to continue this work and to apply it to new areas of emerging importance. The specific aims are fourfold: 1) to evaluate new and existing methods for controlling confounding and tail count variability in case-control genome-wide association (GWA) studies; 2) to evaluate risks associated with missense mutations of unknown significance in genes of established disease relevance; 3) to combine multiple independent sources of data in assessing the joint carcinogenic effects of groups of genes; and 4) to integrate data on tumor and patient characteristics for improved assessment of phenotype-specific etiology. We will evaluate the new methods by simulations, and we will illustrate them by application to existing data on cancers of the breast, ovary and prostate, and emerging data from GWA studies of breast and prostate cancer. The existing data have been collected either by the investigators and the consultants to this project, or as part of three collaborations in which the investigators participate: the Breast Cancer Family Registry (Breast-CFR), the Ovarian Cancer Association Consortium (OCAC), and the International Consortium for Prostate Cancer Genetics (ICPCG). In summary, we need sound, reliable methods for analyzing the vast amounts of emerging genetic data from individuals with and without a given type of cancer. The goals of this research are to develop such methods, and thereby to help generate new knowledge useful for cancer prevention and treatment.

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Publications

Optimal Designs For Estimating Penetrance Of Rare Mutations Of A Disease-susceptibility Gene
Authors: Gong G. , Whittemore A.S. .
Source: Genetic Epidemiology, 2003 Apr; 24(3), p. 173-80.
PMID: 12652521
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Genetic Association Tests For Family Data With Missing Parental Genotypes: A Comparison
Authors: Whittemore A.S. , Halpern J. .
Source: Genetic Epidemiology, 2003 Jul; 25(1), p. 80-91.
PMID: 12813729
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Classifying Disease Chromosomes Arising From Multiple Founders, With Application To Fine-scale Haplotype Mapping
Authors: Yu K. , Martin R.B. , Whittemore A.S. .
Source: Genetic Epidemiology, 2004 Nov; 27(3), p. 173-81.
PMID: 15389930
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Covariate Adjustment In Family-based Association Studies
Authors: Whittemore A.S. , Halpern J. , Ahsan H. .
Source: Genetic Epidemiology, 2005 Apr; 28(3), p. 244-55.
PMID: 15593089
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Prevalence Of Brca1 Mutation Carriers Among U.s. Non-hispanic Whites
Authors: Whittemore A.S. , Gong G. , John E.M. , McGuire V. , Li F.P. , Ostrow K.L. , Dicioccio R. , Felberg A. , West D.W. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2004 Dec; 13(12), p. 2078-83.
PMID: 15598764
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Prostate Specific Antigen Levels In Young Adulthood Predict Prostate Cancer Risk: Results From A Cohort Of Black And White Americans
Authors: Whittemore A.S. , Cirillo P.M. , Feldman D. , Cohn B.A. .
Source: The Journal Of Urology, 2005 Sep; 174(3), p. 872-6; discussion 876.
PMID: 16093978
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Getting More From Digital Snp Data
Authors: El Karoui N. , Zhou W. , Whittemore A.S. .
Source: Statistics In Medicine, 2006-09-30 00:00:00.0; 25(18), p. 3124-33.
PMID: 16397858
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Nonparametric Linkage Analysis Using Person-specific Covariates
Authors: Whittemore A.S. , Halpern J. .
Source: Genetic Epidemiology, 2006 Jul; 30(5), p. 369-79.
PMID: 16671107
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Sex Steroid Hormones In Young Manhood And The Risk Of Subsequent Prostate Cancer: A Longitudinal Study In African-americans And Caucasians (united States)
Authors: Tsai C.J. , Cohn B.A. , Cirillo P.M. , Feldman D. , Stanczyk F.Z. , Whittemore A.S. .
Source: Cancer Causes & Control : Ccc, 2006 Dec; 17(10), p. 1237-44.
PMID: 17111254
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Assessing Environmental Modifiers Of Disease Risk Associated With Rare Mutations
Authors: Whittemore A.S. .
Source: Human Heredity, 2007; 63(2), p. 134-43.
PMID: 17283442
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Comparison Of Admixture And Association Mapping In Admixed Families
Authors: Clarke G. , Whittemore A.S. .
Source: Genetic Epidemiology, 2007 Nov; 31(7), p. 763-75.
PMID: 17508341
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Significance Levels For Studies With Correlated Test Statistics
Authors: Shi J. , Levinson D.F. , Whittemore A.S. .
Source: Biostatistics (oxford, England), 2008 Jul; 9(3), p. 458-66.
PMID: 18089626
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Prevalence Of Pathogenic Brca1 Mutation Carriers In 5 Us Racial/ethnic Groups
Authors: John E.M. , Miron A. , Gong G. , Phipps A.I. , Felberg A. , Li F.P. , West D.W. , Whittemore A.S. .
Source: Jama, 2007-12-26 00:00:00.0; 298(24), p. 2869-76.
PMID: 18159056
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Performance Of Prediction Models For Brca Mutation Carriage In Three Racial/ethnic Groups: Findings From The Northern California Breast Cancer Family Registry
Authors: Kurian A.W. , Gong G.D. , John E.M. , Miron A. , Felberg A. , Phipps A.I. , West D.W. , Whittemore A.S. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2009 Apr; 18(4), p. 1084-91.
PMID: 19336551
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