Grant Number:	1R01CA131324-01A2 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:	2009

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.




Potentially functional variants of CHMP4A and PANX1 in the pyroptosis-related pathway predict survival of patients with non-oropharyngeal head and neck squamous cell carcinoma.
Authors: Tang X. , Wang H. , Liu H. , Li G. , Sturgis E.M. , Shete S. , Wei Q. .
Source: Molecular Carcinogenesis, 2024 Sep; 63(9), p. 1712-1721.
EPub date: 2024-06-11 00:00:00.0.
PMID: 38860607
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An Approach to Identifying Spatial Variability in Observed Infectious Disease Spread in a Prospective Time-Space Series with Applications to COVID-19 and Dengue Incidence.
Authors: Wu C.C. , Chen C.H. , Wang S.R. , Shete S. .
Source: Research Square, 2024-01-24 00:00:00.0; , .
EPub date: 2024-01-24 00:00:00.0.
PMID: 38343818
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Genetic variants in CYP2B6 and HSD17B12 associated with risk of squamous cell carcinoma of the head and neck.
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Source: International Journal Of Cancer, 2022-04-11 00:00:00.0; , .
EPub date: 2022-04-11 00:00:00.0.
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Oral microbiome and onset of oral mucositis in patients with squamous cell carcinoma of the head and neck.
Authors: Reyes-Gibby C.C. , Wang J. , Zhang L. , Peterson C.B. , Do K.A. , Jenq R.R. , Shelburne S. , Shah D.P. , Chambers M.S. , Hanna E.Y. , et al. .
Source: Cancer, 2020-09-05 00:00:00.0; , .
EPub date: 2020-09-05 00:00:00.0.
PMID: 32888342
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A Genome-Wide Association Study Identifies Two Novel Susceptible Regions for Squamous Cell Carcinoma of the Head and Neck.
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Source: Cancer Research, 2020-06-15 00:00:00.0; 80(12), p. 2451-2460.
EPub date: 2020-04-10 00:00:00.0.
PMID: 32276964
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An approach to estimate bidirectional mediation effects with application to body mass index and fasting glucose.
Authors: Talluri R. , Shete S. .
Source: Annals Of Human Genetics, 2018-07-11 00:00:00.0; , .
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Authors: Reyes-Gibby C.C. , Wang J. , Silvas M.R. , Yu R.K. , Hanna E.Y. , Shete S. .
Source: Scientific Reports, 2016-09-27 00:00:00.0; 6, p. 34206.
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Time-varying Smart Design And Data Analysis Methods For Evaluating Adaptive Intervention Effects
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Using The Weighted Area Under The Net Benefit Curve For Decision Curve Analysis
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Source: Bmc Medical Informatics And Decision Making, 2016-07-18 00:00:00.0; 16, p. 94.
PMID: 27431531
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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, 2016-04-22 00:00:00.0; 17, p. 177.
EPub date: 2016-04-22 00:00:00.0.
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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, 2016-02-13 00:00:00.0; 17, p. 40.
EPub date: 2016-02-13 00:00:00.0.
PMID: 26872611
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Evaluating Methods For Modeling Epistasis Networks With Application To Head And Neck Cancer
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Source: Cancer Informatics, 2015; 14(Suppl 2), p. 17-23.
PMID: 25733798
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Informative gene network for chemotherapy-induced peripheral neuropathy.
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Source: Biodata Mining, 2015; 8, p. 24.
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A Risk Prediction Model For Smoking Experimentation In Mexican American Youth
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A linkage disequilibrium-based approach to selecting disease-associated rare variants.
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