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Grant Details

Grant Number: 5R01CA097386-05 Interpret this number
Primary Investigator: Zheng, Wei
Organization: Vanderbilt University
Project Title: Tumor Markers and Recurrent Adenomas: a Follow-Up Study
Fiscal Year: 2006
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Abstract

DESCRIPTION (provided by applicant): Most colorectal cancers arise from adenomatous polyps, and a large proportion of patients with adenomas will develop recurrent adenomas. There is considerable controversy regarding the appropriate surveillance interval following initial colonoscopy. Studies assessing predictors for recurrent adenomas will provide valuable information for designing individualized surveillance strategies, particularly for patients with either multiple adenomas or pathologically advanced adenoma. We propose in this application to recruit and follow 2000 patients diagnosed in 1996 to 2001 with incident multiple or advanced adenomas to evaluate the utility of a panel of promising tumor markers in predicting the risk of adenoma recurrence. The tumor markers proposed for this study reflect major events that occur during the formation and progression of adenomas. Specifically, we will evaluate the following four groups of tumor markers in relation to the risk of adenoma recurrence: 1) proliferation and apoptosis, including the apoptosis index (TUNEL assay) and the expression of Ki-67 (Mibl), epidermal growth factor receptor (EGFR), and transforming growth factor B receptor type II (TGF-J3 RI]); 2) genomic instability - loss of heterozygosity (LOH) events on chromosomes 5q, l7p, 15q, ip, and 18q; 3) Wingless/Writ signaling pathway - expression of the CTTNB1 (Beta-catenin gene), Cyclin D1 CMYC, and COX2 gene products; and 4) DNA methylation - methylation status of the promoters of the MLH1, MGMT, CDKN2A/P16, and APC. Study patients will be followed through a combination of telephone interviews and medical chart reviews. Paraffin-embedded blocks of initial adenomas will be retrieved for bioassays of tumor markers. The diagnosis of initial and recurrent adenomas will be reviewed and confirmed by study pathologists. This study is likely to provide valuable information for identifying high-risk adenoma patients for close surveillance and chemoprevention.

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Publications

Inhibition of 11beta-hydroxysteroid dehydrogenase type II selectively blocks the tumor COX-2 pathway and suppresses colon carcinogenesis in mice and humans.
Authors: Zhang MZ, Xu J, Yao B, Yin H, Cai Q, Shrubsole MJ, Chen X, Kon V, Zheng W, Pozzi A, Harris RC
Source: J Clin Invest, 2009 Apr;119(4), p. 876-85.
EPub date: 2009 Mar 23.
PMID: 19307727
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The relation of magnesium and calcium intakes and a genetic polymorphism in the magnesium transporter to colorectal neoplasia risk.
Authors: Dai Q, Shrubsole MJ, Ness RM, Schlundt D, Cai Q, Smalley WE, Li M, Shyr Y, Zheng W
Source: Am J Clin Nutr, 2007 Sep;86(3), p. 743-51.
PMID: 17823441
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The interaction of age and hormone replacement therapy on colon adenoma risk.
Authors: Murff HJ, Shrubsole MJ, Smalley WE, Wu H, Shyr Y, Ness RM, Zheng W
Source: Cancer Detect Prev, 2007;31(2), p. 161-5.
EPub date: 2007 Apr 11.
PMID: 17433566
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Meat and meat-mutagen intake, doneness preference and the risk of colorectal polyps: the Tennessee Colorectal Polyp Study.
Authors: Shin A, Shrubsole MJ, Ness RM, Wu H, Sinha R, Smalley WE, Shyr Y, Zheng W
Source: Int J Cancer, 2007 Jul 1;121(1), p. 136-42.
PMID: 17354224
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Immunohistochemical expressions of Ki-67, cyclin D1, beta-catenin, cyclooxygenase-2, and epidermal growth factor receptor in human colorectal adenoma: a validation study of tissue microarrays.
Authors: Su Y, Shrubsole MJ, Ness RM, Cai Q, Kataoka N, Washington K, Zheng W
Source: Cancer Epidemiol Biomarkers Prev, 2006 Sep;15(9), p. 1719-26.
PMID: 16985035
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