Diet and Inflammation in Colorectal Cancer Prevention Open Access

Daniel, Carrie Rose (2008)

Permanent URL: https://etd.library.emory.edu/concern/etds/kk91fk76x?locale=en
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Abstract

There is no complete agreement as to which aspects of diet prevent or promote colorectal cancer (CRC). Some of the most salient mechanisms are related to growth and inflammation, but biomarkers are needed to bridge the gap between observational and experimental evidence.

We investigated the association between diet and CRC risk on two levels: in normal-appearing colorectal mucosa, where early risk is believed to be expressed, and in a U.S. cohort followed for CRC between 1999 and 2005. In the Markers of Adenomatous Polyps (MAP) II colonoscopy-based, case-control study (n=203), we investigated TGF-α, TGF-β1, and COX-2 expression as biomarkers of risk for incident sporadic colorectal adenoma. In the Cancer Prevention Study (CPS) II Nutrition Cohort, we prospectively investigated dietary intakes of omega-6 and omega-3 fatty acids, separately and in a ratio, with CRC incidence (778 cases in 96,152 men and women).

In the MAP II study, we found that expression of TGF-α, and the ratio of TGF-α to TGF-β1, was higher in cases than controls (Pdiff<0.05) and directly associated with adenoma (Odds Ratios: 2.23 and 1.40, respectively). COX-2 and TGF-α expression appeared to vary by nonsteroidal antiinflammatory drug (NSAID)-use; otherwise COX-2 did not differ by case-control status. All markers were associated with inflammatory risk factors for CRC. In the CPS II study, the ratio of omega-6 to omega-3 intake was not associated with CRC risk. In women, marine omega-3 intake was associated with a 20-30% lower risk, particularly in rare NSAID-users. Total omega-6 intake was inversely associated with CRC risk in men [Relative Risk (RR): 0.79; Ptrend = 0.07], and alpha-linolenic acid, the primary contributor to total omega-3 intake, was associated with increased risk in women (RR: 1.47; Ptrend=0.10).

TGF-α showed the most promise as a biomarker of risk for colorectal cancer, although other markers also appeared be modulated by inflammatory risk factors. In the U.S. cohort, marine omega-3 and omega-6 intake were associated with lower risk of CRC in women and men, respectively. Future epidemiologic research should continue to search for means to translate early pathways of risk within the colon to larger studies of diet and CRC.

Table of Contents

Chapter 1 Page 1 Introduction…………………………………………………………………………..1 Background and Significance………………………………………………………..2 Corresponding Figures 1-3………………………………………………......17 Chapter 2 Manuscripts 20 TGF-α expression as a potential biomarker of risk within the normal-appearing colorectal mucosa of patients with and without incident sporadic adenoma……...21 Corresponding Figures 1-3 and Tables 1-4…………………………………..41 Phenotypic expression of inflammation and growth mediators COX-2, TGF-β1, and TGF-α in human rectal mucosa………………………..….48

Corresponding Tables 1-3………………………………………………...….61

MAP II Study, Appendix Tables…………………………………………….64

Dietary intake of omega-6 and omega-3 fatty acids and risk of colorectal cancer in a prospective cohort of U.S. men and women………………………………………66

Corresponding Tables 1-5………………....………………84

Chapter 3 Conclusions and Future Directions 90 References


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