One major area of etiological research to which the Cooperative Family Registry for Colorectal Cancer Studies (Colon CFR) is committed is candidate gene association studies. The present application addresses genotypes as well as biomarkers involved in the oxidative stress pathway. We have the following specific aims. 1. To conduct a family-based case-control association study of oxidative stress-related genes, including myeloperoxidase (MPO), endothelial cell nitric oxide synthase (ecNOS), manganese superoxide dismutase (MnSOD), selenium-dependent glutathione peroxidase (GPX1), catalase (CAT), glutathione S- transferase A1 (GSTA1), glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), glutathione S-transferase P1 (GSTP1), NAD(P)H:quinone oxidoreductase (NQ01), catechol-O-methyl transferase (COMT), paraoxonase 1 (PON1), heme oxygenase (HO1), and peroxisome proliferator activated receptor gamma (PPARg), in colorectal cancer development. 1.1. To assess the potential modifying effects of the candidate genes on protective factors for colorectal cancer, including marine n-3 fatty acids, non-steroidal anti-inflammatory drugs (NSAIDs), physical exercise, dietary isothiocyanates (ITC), vitamin D and calcium, and folate. 1.2. To assess the potential modifying effects of the candidate genes on the positive association between alcohol intake and colorectal cancer risk. 2. To determine if certain protective (marine n-3 fatty acids, NSAIDs, physical exercise, ITC, vitamin D and calcium, and folate) and risk-enhancing (alcohol intake) factors for colorectal cancer are associated with plasma lipid peroxidation products [malondialdehyde, (MDA) and lipid peroxides] among controls. 2.1. To determine if oxidative stress- related genes are associated with lipid peroxidation products (MDA and lipid peroxides) among control subjects. 2.2. To determine if the protective/risk factor-lipid peroxidation associations are modified by oxidative stress-related genes. 3. To conduct a family-based case-control association study to assess the role of plasma lipid peroxidation products in colorectal cancer development using an exploratory analyses with a latent variable approach. 4. To conduct a case-case association study to determine if morphological markers of apoptosis in tumor and surrounding free tissue differ among cases with varying exposure levels of a given putative environmental/genetic risk factor. ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA114472-02
Application #
7278179
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Sansbury, Leah B
Project Start
2006-09-01
Project End
2010-07-31
Budget Start
2007-08-01
Budget End
2008-07-31
Support Year
2
Fiscal Year
2007
Total Cost
$528,375
Indirect Cost
Name
University of Southern California
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
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Gago-Dominguez, Manuela; Castelao, Jose Esteban (2008) Role of lipid peroxidation and oxidative stress in the association between thyroid diseases and breast cancer. Crit Rev Oncol Hematol 68:107-14
Gago-Dominguez, Manuela; Jiang, Xuejuan; Castelao, J Esteban (2007) Lipid peroxidation, oxidative stress genes and dietary factors in breast cancer protection: a hypothesis. Breast Cancer Res 9:201