Colorectal cancer is the third most common cancer and the second leading cause of cancer related mortality in the United States. Chronic inflammation and genotoxic free radicals are contributors to colorectal carcinogenesis. As such, our long-term goals are to identify and evaluate lifestyle and dietary factors that can reduce the risk of colorectal cancer through direct modulation of oxidative stress and chronic inflammation. Eicosapentanoic acid is an omega-3 polyunsaturated fatty acid found predominately in marine fish and has consistently demonstrated cancer inhibitory activity in animal models. Eicosapentanoic acid exhibits anti- inflammatory actions while arachidonic acid, an omega-6 polyunsaturated fatty acid, appears pro- inflammatory. Our overarching hypothesis is that individuals with increased dietary ratios of arachidonic acid to eicosapentanoic acid will have an increased risk of colorectal adenoma and that this increased risk is mediated through pro-inflammatory eicosanoids and increased oxidative stress.
The specific aims of this research proposal are: 1) To test the hypothesis that a greater erythrocyte phospholipid membrane arachidonic acid to eicosapentanoic acid ratio is associated with an increased risk of colorectal adenomas;2) To test the hypothesis that an increase in urinary levels of F2-isoprostanes is associated with an increase risk of colorectal adenomas while an increase in urinary levels of F3-isoprostanes is associated with a decreased risk of colorectal adenomas and;3) To test the hypothesis that a greater arachidonic acid to eicosapentanoic acid ratio is associated with increased levels of prostaglandin E2 and urinary F2-isoprostanes and decreased levels of urinary F3-isoprostanes. To complete these aims we will perform a case-control study of 700, non-advanced colorectal adenomas, 350 advanced colorectal adenoma cases and 1050 polyp-free controls using data collected as part of the Tennessee Colorectal Polyp Study. Our research team is uniquely qualified to complete these aims as all samples and clinical data needed for the study have been collected as part of the on-going Tennessee Colorectal Polyp Study, the largest colonoscopy-based adenoma case-control study in the United States. In addition, our colleagues at Vanderbilt University are global leaders in eicosanoid research. The results from these experiments will contribute to our understanding of the colorectal cancer protective ability of eicosapentanoic acid in humans as well as potential mechanisms underlying this effect.

Public Health Relevance

Colorectal cancer is the second leading cause of cancer related mortality in the United States. Omega-3 fatty acids, as found in fish and fish oil supplements, are being increasingly consumed because of their reported anti-inflammatory properties. The purpose of this study is to determine if omega-3 fatty acids reduce the risk of colorectal adenomas and diminishes the production of inflammatory and oxidative stress biomarkers.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA143288-02
Application #
8112012
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Seifried, Harold E
Project Start
2010-08-01
Project End
2014-05-31
Budget Start
2011-06-01
Budget End
2012-05-31
Support Year
2
Fiscal Year
2011
Total Cost
$302,493
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Murff, Harvey J; Roumie, Christianne L; Greevy, Robert A et al. (2018) Metformin use and incidence cancer risk: evidence for a selective protective effect against liver cancer. Cancer Causes Control 29:823-832
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
Coppola, John-Anthony; Shrubsole, Martha J; Cai, Qiuyin et al. (2015) Plasma lipid levels and colorectal adenoma risk. Cancer Causes Control 26:635-43
Murff, Harvey J; Edwards, Todd L (2014) Endogenous Production of Long-Chain Polyunsaturated Fatty Acids and Metabolic Disease Risk. Curr Cardiovasc Risk Rep 8:
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
Murff, Harvey J (2012) Cohort analysis finds that the proportion of people who meet high risk criteria for colorectal, breast or prostate cancer screening based on family history increases between age 30 and 50. Evid Based Med 17:50-1
Cohen, Sarah S; Murff, Harvey J; Signorello, Lisa B et al. (2012) Obesity and colorectal cancer screening among black and white adults. Cancer Causes Control 23:709-16
Edwards, Todd L; Shrubsole, Martha J; Cai, Qiuyin et al. (2012) A study of prostaglandin pathway genes and interactions with current nonsteroidal anti-inflammatory drug use in colorectal adenoma. Cancer Prev Res (Phila) 5:855-63
Dorjgochoo, Tsogzolmaa; Gao, Yu-Tang; Chow, Wong-Ho et al. (2011) Obesity, age, and oxidative stress in middle-aged and older women. Antioxid Redox Signal 14:2453-60
Murff, Harvey J; Shrubsole, Martha J; Chen, Zhi et al. (2011) Nonsteroidal anti-inflammatory drug use and risk of adenomatous and hyperplastic polyps. Cancer Prev Res (Phila) 4:1799-807

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