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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

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 Oct 25;13, p. 498.
EPub date: 2013 Oct 25.
PMID: 24161199
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Association of AMP-activated protein kinase with risk and progression of non-Hodgkin lymphoma.
Authors: Hoffman AE, Demanelis K, Fu A, Zheng T, Zhu Y
Source: Cancer Epidemiol Biomarkers Prev, 2013 Apr;22(4), p. 736-44.
EPub date: 2013 Feb 8.
PMID: 23396962
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Targetome profiling, pathway analysis and genetic association study implicate miR-202 in lymphomagenesis.
Authors: Hoffman AE, Liu R, Fu A, Zheng T, Slack F, Zhu Y
Source: Cancer Epidemiol Biomarkers Prev, 2013 Mar;22(3), p. 327-36.
EPub date: 2013 Jan 18.
PMID: 23334589
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Phenotypic effects of the circadian gene Cryptochrome 2 on cancer-related pathways.
Authors: Hoffman AE, Zheng T, Ba Y, Stevens RG, Yi CH, Leaderer D, Zhu Y
Source: BMC Cancer, 2010 Mar 24;10, p. 110.
EPub date: 2010 Mar 24.
PMID: 20334671
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The core circadian gene Cryptochrome 2 influences breast cancer risk, possibly by mediating hormone signaling.
Authors: Hoffman AE, Zheng T, Yi CH, Stevens RG, Ba Y, Zhang Y, Leaderer D, Holford T, Hansen J, Zhu Y
Source: Cancer Prev Res (Phila), 2010 Apr;3(4), p. 539-48.
EPub date: 2010 Mar 16.
PMID: 20233903
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CLOCK in breast tumorigenesis: genetic, epigenetic, and transcriptional profiling analyses.
Authors: Hoffman AE, Yi CH, Zheng T, Stevens RG, Leaderer D, Zhang Y, Holford TR, Hansen J, Paulson J, Zhu Y
Source: Cancer Res, 2010 Feb 15;70(4), p. 1459-68.
EPub date: 2010 Feb 2.
PMID: 20124474
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Testing the circadian gene hypothesis in prostate cancer: a population-based case-control study.
Authors: Zhu Y, Stevens RG, Hoffman AE, Fitzgerald LM, Kwon EM, Ostrander EA, Davis S, Zheng T, Stanford JL
Source: Cancer Res, 2009 Dec 15;69(24), p. 9315-22.
PMID: 19934327
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The circadian gene NPAS2 is a novel prognostic biomarker for breast cancer.
Authors: Yi C, Mu L, de la Longrais IA, Sochirca O, Arisio R, Yu H, Hoffman AE, Zhu Y, Katsaro D
Source: Breast Cancer Res Treat, 2010 Apr;120(3), p. 663-9.
EPub date: 2009 Aug 1.
PMID: 19649706
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microRNA miR-196a-2 and breast cancer: a genetic and epigenetic association study and functional analysis.
Authors: Hoffman AE, Zheng T, Yi C, Leaderer D, Weidhaas J, Slack F, Zhang Y, Paranjape T, Zhu Y
Source: Cancer Res, 2009 Jul 15;69(14), p. 5970-7.
EPub date: 2009 Jun 30.
PMID: 19567675
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Cancer-related transcriptional targets of the circadian gene NPAS2 identified by genome-wide ChIP-on-chip analysis.
Authors: Yi CH, Zheng T, Leaderer D, Hoffman A, Zhu Y
Source: Cancer Lett, 2009 Nov 1;284(2), p. 149-56.
EPub date: 2009 May 19.
PMID: 19457610
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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 AE, Zheng T, Stevens RG, Ba Y, Zhang Y, Leaderer D, Yi C, Holford TR, Zhu Y
Source: Cancer Res, 2009 Apr 15;69(8), p. 3605-13.
EPub date: 2009 Mar 24.
PMID: 19318546
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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 LJ, Ratner E, Leng S, Zhai R, Nallur S, Babar I, Muller RU, Straka E, Su L, Burki EA, Crowell RE, Patel R, Kulkarni T, Homer R, Zelterman D, Kidd KK, Zhu Y, Christiani DC, Belinsky SA, Slack FJ, Weidhaas JB
Source: Cancer Res, 2008 Oct 15;68(20), p. 8535-40.
PMID: 18922928
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The circadian gene NPAS2, a putative tumor suppressor, is involved in DNA damage response.
Authors: Hoffman AE, Zheng T, Ba Y, Zhu Y
Source: Mol Cancer Res, 2008 Sep;6(9), p. 1461-8.
PMID: 18819933
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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: Mutat Res, 2008 Mar 1;639(1-2), p. 80-8.
EPub date: 2007 Nov 26.
PMID: 18191955
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Clock-cancer connection in non-Hodgkin's lymphoma.
Authors: Zhu Y, Zheng T
Source: Med Hypotheses, 2008;70(4), p. 788-92.
EPub date: 2007 Nov 1.
PMID: 17935900
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Non-synonymous polymorphisms in the circadian gene NPAS2 and breast cancer risk.
Authors: Zhu Y, Stevens RG, Leaderer D, Hoffman A, Holford T, Zhang Y, Brown HN, Zheng T
Source: Breast Cancer Res Treat, 2008 Feb;107(3), p. 421-5.
EPub date: 2007 Apr 24.
PMID: 17453337
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