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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Epidemiology and Disease Control Subcommittee 2 (EDC)
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Gillanders, Elizabeth
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Vanderbilt University Medical Center
Internal Medicine/Medicine
Schools of Medicine
United States
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Davenport, James R; Su, Timothy; Zhao, Zhiguo et al. (2018) Modifiable lifestyle factors associated with risk of sessile serrated polyps, conventional adenomas and hyperplastic polyps. Gut 67:456-465
Rifkin, Samara B; Shrubsole, Martha J; Cai, Qiuyin et al. (2017) PUFA levels in erythrocyte membrane phospholipids are differentially associated with colorectal adenoma risk. Br J Nutr 117:1615-1622
Su, Timothy; Washington, M Kay; Ness, Reid M et al. (2017) Comparison of biomarker expression between proximal and distal colorectal adenomas: The Tennessee-Indiana Adenoma Recurrence Study. Mol Carcinog 56:761-773
Davenport, James R; Cai, Qiuyin; Ness, Reid M et al. (2016) Evaluation of pro-inflammatory markers plasma C-reactive protein and urinary prostaglandin-E2 metabolite in colorectal adenoma risk. Mol Carcinog 55:1251-61
Coppola, John-Anthony; Shrubsole, Martha J; Cai, Qiuyin et al. (2015) Plasma lipid levels and colorectal adenoma risk. Cancer Causes Control 26:635-43
Coleman, Helen G; Ness, Reid M; Smalley, Walter E et al. (2015) Aspects of dietary carbohydrate intake are not related to risk of colorectal polyps in the Tennessee Colorectal Polyp Study. Cancer Causes Control 26:1197-202
Shrubsole, Martha J; Wagner, Conrad; Zhu, Xiangzhu et al. (2015) Associations between S-adenosylmethionine, S-adenosylhomocysteine, and colorectal adenoma risk are modified by sex. Am J Cancer Res 5:458-65
Fu, Zhenming; Shrubsole, Martha J; Smalley, Walter E et al. (2014) Associations between dietary fiber and colorectal polyp risk differ by polyp type and smoking status. J Nutr 144:592-8
Fu, Zhenming; Shrubsole, Martha J; Li, Guoliang et al. (2013) Interaction of cigarette smoking and carcinogen-metabolizing polymorphisms in the risk of colorectal polyps. Carcinogenesis 34:779-86
Murff, Harvey J; Shrubsole, Martha J; Cai, Qiuyin et al. (2012) Dietary intake of PUFAs and colorectal polyp risk. Am J Clin Nutr 95:703-12

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