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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


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 -86¿C. 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.


Associations of Circulating 25-Hydroxyvitamin D3 Concentrations With Incident, Sporadic Colorectal Adenoma Risk According to Common Vitamin D-Binding Protein Isoforms.
Authors: Gibbs D.C. , Fedirko V. , Um C. , Gross M.D. , Thyagarajan B. , Bostick R.M. .
Source: American journal of epidemiology, 2018-09-01; 187(9), p. 1923-1930.
PMID: 29788105
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Associations of mitochondrial polymorphisms with sporadic colorectal adenoma.
Authors: Thyagarajan B. , Guan W. , Fedirko V. , Barcelo H. , Ramasubramaian R. , Gross M. , Goodman M. , Bostick R.M. .
Source: Molecular carcinogenesis, 2018 May; 57(5), p. 598-605.
EPub date: 2018-02-01.
PMID: 29323753
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A Novel Application of Structural Equation Modeling Estimates the Association between Oxidative Stress and Colorectal Adenoma.
Authors: Eldridge R.C. , Goodman M. , Bostick R.M. , Fedirko V. , Gross M. , Thyagarajan B. , Flanders W.D. .
Source: Cancer prevention research (Philadelphia, Pa.), 2018 Jan; 11(1), p. 52-58.
EPub date: 2017-10-26.
PMID: 29074536
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DNA base excision repair genetic risk scores, oxidative balance, and incident, sporadic colorectal adenoma.
Authors: Wang T. , Goodman M. , Sun Y.V. , Thyagarajan B. , Gross M. , Bostick R.M. .
Source: Molecular carcinogenesis, 2017 Jun; 56(6), p. 1642-1652.
EPub date: 2017-02-23.
PMID: 28120344
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Associations of Calcium and Milk Product Intakes with Incident, Sporadic Colorectal Adenomas.
Authors: Um C.Y. , Fedirko V. , Flanders W.D. , Judd S.E. , Bostick R.M. .
Source: Nutrition and cancer, 2017 Apr; 69(3), p. 416-427.
EPub date: 2017-01-27.
PMID: 28128980
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Paleolithic and Mediterranean Diet Pattern Scores Are Inversely Associated with Biomarkers of Inflammation and Oxidative Balance in Adults.
Authors: Whalen K.A. , McCullough M.L. , Flanders W.D. , Hartman T.J. , Judd S. , Bostick R.M. .
Source: The Journal of nutrition, 2016 Jun; 146(6), p. 1217-26.
EPub date: 2016-04-20.
PMID: 27099230
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Effects of supplemental vitamin D and calcium on normal colon tissue and circulating biomarkers of risk for colorectal neoplasms.
Authors: Bostick R.M. .
Source: The Journal of steroid biochemistry and molecular biology, 2015 Apr; 148, p. 86-95.
EPub date: 2015-01-15.
PMID: 25597952
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Oxidative balance score, colorectal adenoma, and markers of oxidative stress and inflammation.
Authors: Kong S.Y. , Bostick R.M. , Flanders W.D. , McClellan W.M. , Thyagarajan B. , Gross M.D. , Judd S. , Goodman M. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2014 Mar; 23(3), p. 545-54.
EPub date: 2014-01-17.
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 M.D. , Fedirko V. , Goodman M. , Bostick R.M. .
Source: Molecular carcinogenesis, 2014 Feb; 53 Suppl 1, p. E193-200.
EPub date: 2013-09-21.
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 M.D. , Goodman M. , Sun Y.V. , Bostick R.M. .
Source: Molecular carcinogenesis, 2014 Feb; 53 Suppl 1, p. E187-92.
EPub date: 2013-06-18.
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 W.D. , Mink P.J. , McCullough M.L. , Bostick R.M. .
Source: American journal of epidemiology, 2013-08-15; 178(4), p. 610-24.
EPub date: 2013-05-02.
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 R.M. .
Source: Annals of epidemiology, 2013 Apr; 23(4), p. 223-6.
EPub date: 2013-01-03.
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 R.M. , Gross M. , Thyagarajan B. , Dash C. , Flanders W.D. .
Source: Annals of epidemiology, 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 R.M. , Goodman M. , Flanders W.D. , Gross M.D. .
Source: American journal of epidemiology, 2010-09-01; 172(5), p. 489-500.
EPub date: 2010-07-22.
PMID: 20650953
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Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status.
Authors: Oz G. , Hutter D. , Tkác I. , Clark H.B. , Gross M.D. , Jiang H. , Eberly L.E. , Bushara K.O. , Gomez C.M. .
Source: Movement disorders : official journal of the Movement Disorder Society, 2010-07-15; 25(9), p. 1253-61.
PMID: 20310029
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