Oxidative Stress, Gamma-tocopherol and Colorectal Adenoma Open Access

Huang, Dina (2015)

Permanent URL: https://etd.library.emory.edu/concern/etds/1g05fc21z?locale=en


Background: Oxidative stress is considered both the initiator and promoter of colorectal carcinogenesis. In this study we examined the use of gamma-tocopherol, a major isoform of vitamin E, as an oxidative biomarker and assessed its association with incident, sporadic colorectal adenoma. We conducted these analyses because the blood levels gamma-tocopherol serve as a reflection of metabolic response to oxidative stress and inflammation rather than a reflection of vitamin E intake. We also extended our analyses by assessing the associations of gamma-tocopherol with oxidative balance score (OBS), and several other biomarkers of oxidative stress and inflammation including F2-isoprostanes (FIP), fluorescent oxidation products (FOP), and C-reactive protein (CRP).

Methods: The research data were obtained from two previous case-control studies of incident, sporadic colorectal adenoma conducted several years apart using similar protocols in two different U.S. states. Gamma-tocopherol levels were categorized into tertile intervals, and OBS was divided into three equal intervals. Gamma-tocopherol and biomarker levels were also dichotomized based on median values among controls. Unconditional logistic regression was used to calculate adjusted odds ratios (ORs) and corresponding 95% Confidence Intervals (95% CIs).

Results: There were no significant associations between gamma-tocopherol (used as a continuous, dichotomized, or three-level variable) and incident, sporadic colorectal adenoma. In the analysis of the association between OBS and gamma-tocopherol, the OR for the middle vs. lowest OBS interval was 0.57 (95% CI: 0.31- 1.04), and the corresponding OR for the highest vs. lowest interval was 0.17 (95% CI: 0.07-0.41; P trend<0.001). FIP was significantly associated with plasma concentrations of gamma-tocopherol; and adjusted ORs for the medium and high levels of gamma-tocopherol were 1.51 (95% CI: 0.79-2.87) and 3.28 (95% CI: 1.58, 6.80) compared to low gamma-tocopherol concentration. None of the corresponding estimates for FOP and CRP were significantly different from the null value.

Conclusion: Although gamma-tocopherol was not associated with colorectal adenoma directly, the significant associations between gamma-tocopherol and OBS/FIP indicate that gamma-tocopehrol may be capable of reflecting oxidation levels. A cohort study is needed to further evaluate this issue.

Table of Contents

Introduction. 1

Oxidative stress and carcinogenesis. 1

Markers of oxidative stress and inflammation and their association with colorectal tumors. 2

Gamma-tocopherol. 4

ocopherols and colon tumors in human population studies. 5

Oxidative Balance Score. 6

Methods. 7

Study population. 7

Data collection and laboratory analyses. 7

Oxidative Balance Score. 9

Statistical analysis. 10

Results. 11

Discussion. 13

References. 16

Tables . 23

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