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. ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA116795-02
Application #
7414074
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Mahabir, Somdat
Project Start
2007-05-01
Project End
2010-04-30
Budget Start
2008-05-01
Budget End
2009-04-30
Support Year
2
Fiscal Year
2008
Total Cost
$286,379
Indirect Cost
Name
Emory University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Eldridge, Ronald C; Goodman, Michael; Bostick, Roberd M et al. (2018) A Novel Application of Structural Equation Modeling Estimates the Association between Oxidative Stress and Colorectal Adenoma. Cancer Prev Res (Phila) 11:52-58
Thyagarajan, Bharat; Guan, Weihua; Fedirko, Veronika et al. (2018) Associations of mitochondrial polymorphisms with sporadic colorectal adenoma. Mol Carcinog 57:598-605
Gibbs, David C; Fedirko, Veronika; Um, Caroline et al. (2018) Associations of Circulating 25-Hydroxyvitamin D3 Concentrations With Incident, Sporadic Colorectal Adenoma Risk According to Common Vitamin D-Binding Protein Isoforms. Am J Epidemiol 187:1923-1930
Wang, Tengteng; Goodman, Michael; Sun, Yan V et al. (2017) DNA base excision repair genetic risk scores, oxidative balance, and incident, sporadic colorectal adenoma. Mol Carcinog 56:1642-1652
Bostick, Roberd M (2015) Effects of supplemental vitamin D and calcium on normal colon tissue and circulating biomarkers of risk for colorectal neoplasms. J Steroid Biochem Mol Biol 148:86-95
Yang, Baiyu; Thyagarajan, Bharat; Gross, Myron D et al. (2014) No evidence that associations of incident, sporadic colorectal adenoma with its major modifiable risk factors differ by chromosome 8q24 region rs6983267 genotype. Mol Carcinog 53 Suppl 1:E193-200
Kong, So Yeon J; Bostick, Roberd M; Flanders, W Dana et al. (2014) Oxidative balance score, colorectal adenoma, and markers of oxidative stress and inflammation. Cancer Epidemiol Biomarkers Prev 23:545-54
Yang, Baiyu; Thyagarajan, Bharat; Gross, Myron D et al. (2014) Genetic variants at chromosome 8q24, colorectal epithelial cell proliferation, and risk for incident, sporadic colorectal adenomas. Mol Carcinog 53 Suppl 1:E187-92
Labadie, Julia; Goodman, Michael; Thyagarajan, Bharat et al. (2013) Associations of oxidative balance-related exposures with incident, sporadic colorectal adenoma according to antioxidant enzyme genotypes. Ann Epidemiol 23:223-6
Dash, Chiranjeev; Goodman, Michael; Flanders, W Dana et al. (2013) Using pathway-specific comprehensive exposure scores in epidemiology: application to oxidative balance in a pooled case-control study of incident, sporadic colorectal adenomas. Am J Epidemiol 178:610-24

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