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Grant Details

Grant Number: 5R01CA090899-10 Interpret this number
Primary Investigator: Zheng, Wei
Organization: Vanderbilt University
Project Title: Molecular Epidemiologic Study of Breast Cancer
Fiscal Year: 2009
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Abstract

Most epidemiological studies of breast cancer have focused on investigations of genetic polymorphisms in the genes involved in estrogen and carcinogen metabolism. A number of promising associations have been identified, many of which have yet to be replicated. In this competitive renewal application, we propose to confirm some of the promising associations identified in the initial funding cycle and extend our work to the investigation of other novel genes in estrogen metabolism and several major genes in the pathways of angiogenesis, extracellular matrix remodeling, inflammatory response, and prostaglandin synthesis. These genes are involved in regulating the tumor microenvironment and are likely related to, not only the prognosis, but also the risk of cancers large enough to be detected clinically. The proposed study will use data and biological samples collected from the Shanghai Breast Cancer Study (RO1CA64277). Genetic polymorphisms in approximately 25 candidate genes will initially be evaluated using both genotype- and haplotype-approaches in approximately 1200 cases and 1200 controls recruited from 1996 to 1998. Promising associations identified in the initial phase will be re-evaluated in the second set of subjects (1300 cases and 1300 controls) recruited since 2002 in the parent study. This 2-phase study design will effectively balance both Type I and Type 2 errors and provide credible results towards our understanding of the etiology of breast cancer. Results from this study will be valuable in identifying high risk women for primary and secondary prevention of breast cancer.

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Publications

Genome-wide association study identifies a common variant associated with risk of endometrial cancer.
Authors: Spurdle AB, Thompson DJ, Ahmed S, Ferguson K, Healey CS, O'Mara T, Walker LC, Montgomery SB, Dermitzakis ET, Australian National Endometrial Cancer Study Group, Fahey P, Montgomery GW, Webb PM, Fasching PA, Beckmann MW, Ekici AB, Hein A, Lambrechts D, Coenegrachts L, Vergote I, Amant F, Salvesen HB, Trovik J, Njolstad TS, Helland H, Scott RJ, Ashton K, Proietto T, Otton G, National Study of Endometrial Cancer Genetics Group, Tomlinson I, Gorman M, Howarth K, Hodgson S, Garcia-Closas M, Wentzensen N, Yang H, Chanock S, Hall P, Czene K, Liu J, Li J, Shu XO, Zheng W, Long J, Xiang YB, Shah M, Morrison J, Michailidou K, Pharoah PD, Dunning AM, Easton DF
Source: Nat Genet, 2011 May;43(5), p. 451-4.
EPub date: 2011 Apr 17.
PMID: 21499250
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The EGFR polymorphism rs884419 is associated with freedom from recurrence in patients with resected prostate cancer.
Authors: Perez CA, Chen H, Shyr Y, Courtney R, Zheng W, Cai Q, Hwang M, Jaboin J, Schleicher S, Moretti L, Wills M, Smith JA, Lu B
Source: J Urol, 2010 May;183(5), p. 2062-9.
EPub date: 2010 Mar 19.
PMID: 20303520
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Mutations in the mitochondrial DNA D-loop region and breast cancer risk.
Authors: Ye C, Shu XO, Pierce L, Wen W, Courtney R, Gao YT, Zheng W, Cai Q
Source: Breast Cancer Res Treat, 2010 Jan;119(2), p. 431-6.
EPub date: 2009 Apr 21.
PMID: 19381801
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Heritable variation of ERBB2 and breast cancer risk.
Authors: Breyer JP, Sanders ME, Airey DC, Cai Q, Yaspan BL, Schuyler PA, Dai Q, Boulos F, Olivares MG, Bradley KM, Gao YT, Page DL, Dupont WD, Zheng W, Smith JR
Source: Cancer Epidemiol Biomarkers Prev, 2009 Apr;18(4), p. 1252-8.
EPub date: 2009 Mar 31.
PMID: 19336545
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A two-stage case-control study of EGFR polymorphisms and breast cancer risk.
Authors: Hong YS, Deming SL, Gao YT, Long JR, Shu XO, Cai Q, Lu W, Zheng W
Source: Cancer Epidemiol Biomarkers Prev, 2009 Feb;18(2), p. 680-3.
EPub date: 2009 Feb 3.
PMID: 19190167
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Association of mitochondrial DNA displacement loop (CA)n dinucleotide repeat polymorphism with breast cancer risk and survival among Chinese women.
Authors: Ye C, Gao YT, Wen W, Breyer JP, Shu XO, Smith JR, Zheng W, Cai Q
Source: Cancer Epidemiol Biomarkers Prev, 2008 Aug;17(8), p. 2117-22.
PMID: 18708405
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Genetic polymorphisms of metastasis suppressor gene NME1 and breast cancer survival.
Authors: Qu S, Long J, Cai Q, Shu XO, Cai H, Gao YT, Zheng W
Source: Clin Cancer Res, 2008 Aug 1;14(15), p. 4787-93.
PMID: 18676749
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ERBB2 genetic polymorphism and breast cancer risk in Chinese women: a population-based case-control study.
Authors: Qu S, Cai Q, Gao YT, Lu W, Cai H, Su Y, Wang SE, Shu XO, Zheng W
Source: Breast Cancer Res Treat, 2008 Jul;110(1), p. 169-76.
EPub date: 2007 Aug 9.
PMID: 17687647
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Haplotype analysis of CYP11A1 identifies promoter variants associated with breast cancer risk.
Authors: Yaspan BL, Breyer JP, Cai Q, Dai Q, Elmore JB, Amundson I, Bradley KM, Shu XO, Gao YT, Dupont WD, Zheng W, Smith JR
Source: Cancer Res, 2007 Jun 15;67(12), p. 5673-82.
PMID: 17575134
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Expression patterns of the ATM gene in mammary tissues and their associations with breast cancer survival.
Authors: Ye C, Cai Q, Dai Q, Shu XO, Shin A, Gao YT, Zheng W
Source: Cancer, 2007 May 1;109(9), p. 1729-35.
PMID: 17366603
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Association of cyclin D1 genotype with breast cancer risk and survival.
Authors: Shu XO, Moore DB, Cai Q, Cheng J, Wen W, Pierce L, Cai H, Gao YT, Zheng W
Source: Cancer Epidemiol Biomarkers Prev, 2005 Jan;14(1), p. 91-7.
PMID: 15668481
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The long-term impact of medical and socio-demographic factors on the quality of life of breast cancer survivors among Chinese women.
Authors: Cui Y, Shu XO, Gao Y, Cai H, Wen W, Ruan ZX, Jin F, Zheng W
Source: Breast Cancer Res Treat, 2004 Sep;87(2), p. 135-47.
PMID: 15377838
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Oral contraceptive use and breast cancer risk: modification by NAD(P)H:quinone oxoreductase (NQO1) genetic polymorphisms.
Authors: Fowke JH, Shu XO, Dai Q, Jin F, Cai Q, Gao YT, Zheng W
Source: Cancer Epidemiol Biomarkers Prev, 2004 Aug;13(8), p. 1308-15.
PMID: 15298951
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Genetic polymorphisms in the human growth hormone-1 gene (GH1) and the risk of breast carcinoma.
Authors: Ren Z, Cai Q, Shu XO, Cai H, Cheng JR, Wen WQ, Gao YT, Zheng W
Source: Cancer, 2004 Jul 15;101(2), p. 251-7.
PMID: 15241820
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