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

Grant Number: 5R01CA131324-04 Interpret this number
Primary Investigator: Shete, Sanjay
Organization: University Of Tx Md Anderson Can Ctr
Project Title: Genome Wide Association Study of Head and Neck Cancer
Fiscal Year: 2012
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Abstract

DESCRIPTION (provided by applicant): Head and neck cancers have well-documented associations with tobacco and alcohol exposure, but the disease develops in only a small fraction of users, which implies an important role for genetic susceptibility. Therefore, head and neck cancers are an excellent model for studying genetic susceptibility to environmental carcinogens. The primary goal of this R01 application is to perform a comprehensive two-stage, high-density, genome-wide single-nucleotide polymorphism (SNP) analysis of head and neck cancer cases and corresponding frequency matched controls to identify novel genetic risk factors for head and neck cancer. This proposal builds upon a well-annotated existing DNA repository of cases and controls. One of the unique features of our study is the availability of DNA repair assay data on most of the cases and controls in this study, which will allow us to conduct genotype/phenotype analyses. We also have access to genome-wide association data from 1200 white control subjects from the same source population. In aim 1, we will perform genotyping on 1000 randomly selected head and neck cancer cases and 500 controls using a 370K Illumina Infinium HapMap HumanCNV370-Duo SNP Chip. We will perform association analyses (1000 cases and 1700 controls) in the first stage using outcome variable as case-control status as well as DNA repair capacity assay data. Our second aim is to perform second-stage analysis of the SNPs selected in stage 1 using 900 additional cases and corresponding controls from the same source and from UCLA. We will use efficient joint analysis of cases and controls from the first and second aims, for a total of 1900 cases and 2600 controls. Finally, in aim 3, we will apply novel statistical tools such as the latent variable approach with Tukey's one-degree-of-freedom test and support vector machines to identify gene-gene and gene-environment (using environmental factors such as smoking and alcohol use) interactions that contribute to the risk of head and neck cancer. We are an experienced investigative team proposing a comprehensive analysis that incorporates epidemiological, behavioral, and functional data. Identification of novel genetic risk factors and their interactions with environmental factors will contribute to the early diagnosis of head and neck cancers. PUBLIC HEALTH RELEVANCE: The identification of novel genetic risk factors and their interactions with environmental factors will contribute to the early diagnosis of the disease and help identify individuals at highest risk for the development of head and neck cancer on the basis of their personal exposure patterns and their genetic risk profiles.

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Publications

Effects Of Measured Susceptibility Genes On Cancer Risk In Family Studies
Authors: Wu C.C. , Strong L.C. , Shete S. .
Source: Human Genetics, 2010 Mar; 127(3), p. 349-57.
PMID: 20039063
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Using Both Cases And Controls For Testing Hardy-weinberg Proportions In A Genetic Association Study
Authors: Wang,J. , Shete,S. .
Source: Human Heredity, 2010; 69(3), p. 212-8.
PMID: 20203526
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Mediating Effects Of Smoking And Chronic Obstructive Pulmonary Disease On The Relation Between The Chrna5-a3 Genetic Locus And Lung Cancer Risk
Authors: Wang J. , Spitz M.R. , Amos C.I. , Wilkinson A.V. , Wu X. , Shete S. .
Source: Cancer, 2010-07-15 00:00:00.0; 116(14), p. 3458-62.
PMID: 20564069
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A Powerful Hybrid Approach To Select Top Single-nucleotide Polymorphisms For Genome-wide Association Study
Authors: Wang,J. , Shete,S. .
Source: Bmc Genetics, 2011; 12, p. 3.
PMID: 21211033
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Estimation Of Odds Ratios Of Genetic Variants For The Secondary Phenotypes Associated With Primary Diseases
Authors: Wang,J. , Shete,S. .
Source: Genetic Epidemiology, 2011 Apr; 35(3), p. 190-200.
PMID: 21308766
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Power And Type I Error Results For A Bias-correction Approach Recently Shown To Provide Accurate Odds Ratios Of Genetic Variants For The Secondary Phenotypes Associated With Primary Diseases
Authors: Wang,J. , Shete,S. .
Source: Genetic Epidemiology, 2011 Nov; 35(7), p. 739-43.
PMID: 21769937
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Testing Hardy-weinberg Proportions In A Frequency-matched Case-control Genetic Association Study
Authors: Wang,J. , Shete,S. .
Source: Plos One, 2011; 6(11), p. e27642.
PMID: 22110703
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Using Ascertainment For Targeted Resequencing To Increase Power To Identify Causal Variants
Authors: Swartz M.D. , Peng B. , Reyes-Gibby C. , Shete S. .
Source: Statistics And Its Interface, 2011; 4(3), p. 285-294.
PMID: 22468169
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Analysis Of Secondary Phenotype Involving The Interactive Effect Of The Secondary Phenotype And Genetic Variants On The Primary Disease
Authors: Wang J. , Shete S. .
Source: Annals Of Human Genetics, 2012 Nov; 76(6), p. 484-99.
PMID: 22881407
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False-negative-rate Based Approach For Selecting Top Single-nucleotide Polymorphisms In The First Stage Of A Two-stage Genome-wide Association Study
Authors: Huang Z. , Wang J. , Wu C.C. , Houlston R.S. , Bondy M.L. , Shete S. .
Source: Statistics And Its Interface, 2011; 4(3), p. 359-371.
PMID: 23060946
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Method For Evaluating Multiple Mediators: Mediating Effects Of Smoking And Copd On The Association Between The Chrna5-a3 Variant And Lung Cancer Risk
Authors: Wang J. , Spitz M.R. , Amos C.I. , Wu X. , Wetter D.W. , Cinciripini P.M. , Shete S. .
Source: Plos One, 2012; 7(10), p. e47705.
PMID: 23077662
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Calculation Of Exact P-values When Snps Are Tested Using Multiple Genetic Models
Authors: Talluri R. , Wang J. , Shete S. .
Source: Bmc Genetics, 2014; 15, p. 75.
PMID: 24950707
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X-chromosome Genetic Association Test Accounting For X-inactivation, Skewed X-inactivation, And Escape From X-inactivation
Authors: Wang J. , Yu R. , Shete S. .
Source: Genetic Epidemiology, 2014 Sep; 38(6), p. 483-93.
PMID: 25043884
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A Risk Prediction Model For Smoking Experimentation In Mexican American Youth
Authors: Talluri R. , Wilkinson A.V. , Spitz M.R. , Shete S. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2014 Oct; 23(10), p. 2165-74.
PMID: 25063521
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Evaluating Methods For Modeling Epistasis Networks With Application To Head And Neck Cancer
Authors: Talluri R. , Shete S. .
Source: Cancer Informatics, 2015; 14(Suppl 2), p. 17-23.
PMID: 25733798
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Mapk1/erk2 As Novel Target Genes For Pain In Head And Neck Cancer Patients
Authors: Reyes-Gibby C.C. , Wang J. , Silvas M.R. , Yu R. , Yeung S.C. , Shete S. .
Source: Bmc Genetics, 2016; 17(1), p. 40.
PMID: 26872611
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Empirical Estimation Of Sequencing Error Rates Using Smoothing Splines
Authors: Zhu X. , Wang J. , Peng B. , Shete S. .
Source: Bmc Bioinformatics, 2016; 17, p. 177.
PMID: 27102907
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