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Grant Details

Grant Number: 5R01CA116795-03 Interpret this number
Primary Investigator: Goodman, Michael
Organization: Emory University
Project Title: Oxidative Stress, DNA Repair & Colorectal Adenoma Risk
Fiscal Year: 2009
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Abstract

DESCRIPTION (provided by applicant): The objective of the proposed study is to examine the association between colorectal adenoma and determinants of oxidative stress including dietary habits, serum ferritin (marker of iron intake), biomarkers of oxidative damage, serum antioxidant levels, as well as genetic variation in antioxidant, arachidonic acid- metabolizing (inflammation-related) and DNA repair enzymes. The proposed scope of work (referred to as the 'New Study') is limited to laboratory and statistical analyses using biological samples and questionnaire data from a two previously conducted, and methodologically very similar, colonoscopy-based case-control studies of sporadic colorectal adenoma (Parent studies): one conducted in North Carolina and another conducted in Minnesota. None of the analyses proposed for the New Study were part of the Parent Studies design and scope. Cases included in the Parent Studies were pathology-confirmed, incident adenomatous polyp patients, and controls were patients with no previous history of adenomatous polyps who underwent colonoscopy and were found to be free of adenomatous polyps. The final sample size included 778 cases and 920 controls. All participants completed mailed questionnaires, which included information on family history of polyps or colon cancer, dietary information (through use of a Willett Food Frequency Questionnaire), physical activity, reproductive variables, body fat distribution, and their reason(s) for and the sequence of events leading to colonoscopy. Blood was drawn, processed by various protocols, and stored as Buffy coats, nuclear pellets, serum, and plasma at -86C. The laboratory analysis for the New Study will include measuring biomarkers of oxidative DNA damage (8-OHdG) and lipid peroxidation (isoprostanes), levels of lipid-soluble carotenoids and tocopherols (antioxidants) and serum ferritin (marker of potentially pro- oxidant iron intake), and genotyping for polymorphisms of five antioxidant genes (GSTT1, GSTM1, MnSOD, EC-SOD, and GPX1) and five arachidonic acid-metabolizing genes (COX-2, LOX-5, LOX-12, LOX15 and PPAR-y). We will also evaluate the SNPs of the main genes involved in DNA base excision repair including OGG1, APE1, XRCC1, ERCC5 and several others. The resulting data will be analyzed using multivariate unconditional logistic regression models. Particular attention will be paid to identification of potential gene- gene, gene-lifestyle, and gene-phenotype interactions.

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Publications

Oxidative balance score, colorectal adenoma, and markers of oxidative stress and inflammation.
Authors: Kong SY, Bostick RM, Flanders WD, McClellan WM, Thyagarajan B, Gross MD, Judd S, Goodman M
Source: Cancer Epidemiol Biomarkers Prev, 2014 Mar;23(3), p. 545-54.
EPub date: 2014 Jan 17.
PMID: 24443405
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No evidence that associations of incident, sporadic colorectal adenoma with its major modifiable risk factors differ by chromosome 8q24 region rs6983267 genotype.
Authors: Yang B, Thyagarajan B, Gross MD, Fedirko V, Goodman M, Bostick RM
Source: Mol Carcinog, 2014 Feb;53 Suppl 1, p. E193-200.
EPub date: 2013 Sep 21.
PMID: 24115145
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Genetic variants at chromosome 8q24, colorectal epithelial cell proliferation, and risk for incident, sporadic colorectal adenomas.
Authors: Yang B, Thyagarajan B, Gross MD, Goodman M, Sun YV, Bostick RM
Source: Mol Carcinog, 2014 Feb;53 Suppl 1, p. E187-92.
EPub date: 2013 Jun 18.
PMID: 23776012
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Using pathway-specific comprehensive exposure scores in epidemiology: application to oxidative balance in a pooled case-control study of incident, sporadic colorectal adenomas.
Authors: Dash C, Goodman M, Flanders WD, Mink PJ, McCullough ML, Bostick RM
Source: Am J Epidemiol, 2013 Aug 15;178(4), p. 610-24.
EPub date: 2013 May 2.
PMID: 23639935
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Associations of oxidative balance-related exposures with incident, sporadic colorectal adenoma according to antioxidant enzyme genotypes.
Authors: Labadie J, Goodman M, Thyagarajan B, Gross M, Sun Y, Fedirko V, Bostick RM
Source: Ann Epidemiol, 2013 Apr;23(4), p. 223-6.
EPub date: 2013 Jan 3.
PMID: 23290999
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Combined measure of pro- and anti-oxidant exposures in relation to prostate cancer and colorectal adenoma risk: an update.
Authors: Goodman M, Bostick RM, Gross M, Thyagarajan B, Dash C, Flanders WD
Source: Ann Epidemiol, 2010 Dec;20(12), p. 955-7.
PMID: 21074110
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Blood 25-hydroxyvitamin D3 concentrations and incident sporadic colorectal adenoma risk: a pooled case-control study.
Authors: Fedirko V, Bostick RM, Goodman M, Flanders WD, Gross MD
Source: Am J Epidemiol, 2010 Sep 1;172(5), p. 489-500.
EPub date: 2010 Jul 22.
PMID: 20650953
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Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status.
Authors: Oz G, Hutter D, Tkc I, Clark HB, Gross MD, Jiang H, Eberly LE, Bushara KO, Gomez CM
Source: Mov Disord, 2010 Jul 15;25(9), p. 1253-61.
PMID: 20310029
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