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

Grant Number: 5R01CA122676-03 Interpret this number
Primary Investigator: Zhu, Yong
Organization: Yale University
Project Title: Database of Functional Snps in Cancer-Related Environmentally Responsive Genes
Fiscal Year: 2009
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Abstract

DESCRIPTION (provided by applicant): With millions of single nucleotide polymorphisms (SNPs) identified, there is now a great need for prioritizing potential functional SNPs that are most likely to affect phenotypic functions and ultimately contribute to disease development. This proposal will explore the application of available bioinformatic methods in functional SNP selection by focusing on genes responsible for environmental responses. Validity of these approaches will be assessed by literature search and empirical confirmations. Specifically, the aims of this proposal are: 1) To identify SNPs with potential functional importance in approximately 700 environmentally responsive genes using SNPs collected from public SNP databases and screened by available bioinformatic tools. A functional SNP database will be constructed. 2).To survey previous publications examining SNP functionality and their roles in cancer case-control studies. Results will be integrated with the SNP database. 3) To determine to what extent the predictive value of SNP functionality is mirrored in findings from molecular epidemiologic studies. Since most of these environmentally responsive genes are involved in cancer development, our hypothesis is that SNPs predicted to have significant impact on protein function are more likely to be associated with cancer risk in terms of odds ratios detected in previous case-control studies. Functional SNPs generated from this interdisciplinary approach will become publicly available. Findings from this study will enhance the use of SNPs in future phenotypic studies and molecular epidemiologic approaches to address questions related to gene-environment interaction in disease risk estimate.

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Publications

Non-synonymous Polymorphisms In The Circadian Gene Npas2 And Breast Cancer Risk
Authors: Zhu Y. , Stevens R.G. , Leaderer D. , Hoffman A. , Holford T. , Zhang Y. , Brown H.N. , Zheng T. .
Source: Breast Cancer Research And Treatment, 2008 Feb; 107(3), p. 421-5.
PMID: 17453337
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Clock-cancer Connection In Non-hodgkin's Lymphoma
Authors: Zhu Y. , Zheng T. .
Source: Medical Hypotheses, 2008; 70(4), p. 788-92.
PMID: 17935900
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Correlating Observed Odds Ratios From Lung Cancer Case-control Studies To Snp Functional Scores Predicted By Bioinformatic Tools
Authors: Zhu Y. , Hoffman A. , Wu X. , Zhang H. , Zhang Y. , Leaderer D. , Zheng T. .
Source: Mutation Research, 2008-03-01 00:00:00.0; 639(1-2), p. 80-8.
PMID: 18191955
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The Circadian Gene Npas2, A Putative Tumor Suppressor, Is Involved In Dna Damage Response
Authors: Hoffman A.E. , Zheng T. , Ba Y. , Zhu Y. .
Source: Molecular Cancer Research : Mcr, 2008 Sep; 6(9), p. 1461-8.
PMID: 18819933
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A Snp In A Let-7 Microrna Complementary Site In The Kras 3' Untranslated Region Increases Non-small Cell Lung Cancer Risk
Authors: Chin L.J. , Ratner E. , Leng S. , Zhai R. , Nallur S. , Babar I. , Muller R.U. , Straka E. , Su L. , Burki E.A. , et al. .
Source: Cancer Research, 2008-10-15 00:00:00.0; 68(20), p. 8535-40.
PMID: 18922928
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Clock-cancer Connection In Non-hodgkin's Lymphoma: A Genetic Association Study And Pathway Analysis Of The Circadian Gene Cryptochrome 2
Authors: Hoffman A.E. , Zheng T. , Stevens R.G. , Ba Y. , Zhang Y. , Leaderer D. , Yi C. , Holford T.R. , Zhu Y. .
Source: Cancer Research, 2009-04-15 00:00:00.0; 69(8), p. 3605-13.
PMID: 19318546
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Cancer-related Transcriptional Targets Of The Circadian Gene Npas2 Identified By Genome-wide Chip-on-chip Analysis
Authors: Yi C.H. , Zheng T. , Leaderer D. , Hoffman A. , Zhu Y. .
Source: Cancer Letters, 2009-11-01 00:00:00.0; 284(2), p. 149-56.
PMID: 19457610
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Microrna Mir-196a-2 And Breast Cancer: A Genetic And Epigenetic Association Study And Functional Analysis
Authors: Hoffman A.E. , Zheng T. , Yi C. , Leaderer D. , Weidhaas J. , Slack F. , Zhang Y. , Paranjape T. , Zhu Y. .
Source: Cancer Research, 2009-07-15 00:00:00.0; 69(14), p. 5970-7.
PMID: 19567675
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The Circadian Gene Npas2 Is A Novel Prognostic Biomarker For Breast Cancer
Authors: Yi C. , Mu L. , de la Longrais I.A. , Sochirca O. , Arisio R. , Yu H. , Hoffman A.E. , Zhu Y. , Katsaro D. .
Source: Breast Cancer Research And Treatment, 2010 Apr; 120(3), p. 663-9.
PMID: 19649706
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Testing The Circadian Gene Hypothesis In Prostate Cancer: A Population-based Case-control Study
Authors: Zhu Y. , Stevens R.G. , Hoffman A.E. , Fitzgerald L.M. , Kwon E.M. , Ostrander E.A. , Davis S. , Zheng T. , Stanford J.L. .
Source: Cancer Research, 2009-12-15 00:00:00.0; 69(24), p. 9315-22.
PMID: 19934327
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Clock In Breast Tumorigenesis: Genetic, Epigenetic, And Transcriptional Profiling Analyses
Authors: Hoffman A.E. , Yi C.H. , Zheng T. , Stevens R.G. , Leaderer D. , Zhang Y. , Holford T.R. , Hansen J. , Paulson J. , Zhu Y. .
Source: Cancer Research, 2010-02-15 00:00:00.0; 70(4), p. 1459-68.
PMID: 20124474
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The Core Circadian Gene Cryptochrome 2 Influences Breast Cancer Risk, Possibly By Mediating Hormone Signaling
Authors: Hoffman A.E. , Zheng T. , Yi C.H. , Stevens R.G. , Ba Y. , Zhang Y. , Leaderer D. , Holford T. , Hansen J. , Zhu Y. .
Source: Cancer Prevention Research (philadelphia, Pa.), 2010 Apr; 3(4), p. 539-48.
PMID: 20233903
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Phenotypic Effects Of The Circadian Gene Cryptochrome 2 On Cancer-related Pathways
Authors: Hoffman A.E. , Zheng T. , Ba Y. , Stevens R.G. , Yi C.H. , Leaderer D. , Zhu Y. .
Source: Bmc Cancer, 2010; 10, p. 110.
PMID: 20334671
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Targetome Profiling, Pathway Analysis And Genetic Association Study Implicate Mir-202 In Lymphomagenesis
Authors: Hoffman A.E. , Liu R. , Fu A. , Zheng T. , Slack F. , Zhu Y. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2013 Mar; 22(3), p. 327-36.
PMID: 23334589
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Association Of Amp-activated Protein Kinase With Risk And Progression Of Non-hodgkin Lymphoma
Authors: Hoffman A.E. , Demanelis K. , Fu A. , Zheng T. , Zhu Y. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2013 Apr; 22(4), p. 736-44.
PMID: 23396962
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Potential Cancer-related Role Of Circadian Gene Timeless Suggested By Expression Profiling And In Vitro Analyses
Authors: Mao Y. , Fu A. , Leaderer D. , Zheng T. , Chen K. , Zhu Y. .
Source: Bmc Cancer, 2013; 13, p. 498.
PMID: 24161199
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Targetome Profiling And Functional Genetics Implicate Mir-618 In Lymphomagenesis
Authors: Fu A. , Hoffman A.E. , Liu R. , Jacobs D.I. , Zheng T. , Zhu Y. .
Source: Epigenetics, 2014 May; 9(5), p. 730-7.
PMID: 24503492
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