Experimental biology evidence demonstrating that antioxidants can reverse the effects of oxidative stress-induced damage is not well supported by human studies. Previous research found that combining individual pro- and anti-oxidant factors into a comprehensive oxidative balance score (OBS) can be more strongly associated with various conditions than any individual factor. In three thematically related studies I investigated the associations of OBS with prostate cancer risk (Study 1), with biomarkers of oxidative stress (Study 2), and with indicators of inflammation and cardiovascular health (Study 3).
Study 1 used the Cancer Prevention Study-II Nutrition Cohort (n=43,325). The data on OBS were obtained from baseline questionnaires and prostate cancer cases were ascertained via active follow up. Contrary to expectation, there was no inverse association between OBS and prostate cancer risk.
In Study 2 I investigated the association between OBS and three biomarkers of oxidative stress: F2-isoprostanes (FIP), fluorescent oxidative products (FOP) and mitochondrial DNA (mtDNA) copy number, in the cross-sectional Study of Race, Stress, and Hypertension (n=321). Odds ratios (95% confidence intervals) comparing the highest to lowest OBS tertile for FIP and FOP were 0.10 (0.04 - 0.26; p-trend<0.05), and 3.01 (1.51 - 6.04; p-trend <0.05), respectively.
Using data from the Reasons for Geographic and Racial Differences in Stroke cohort (Study 3), I investigated the relation of OBS to indicators of inflammation (C-reactive protein, white blood cell count, albumin) and cardiovascular health (cholesterol, LDL, HDL, and triglycerides). The odds ratios (95% confidence intervals) comparing the highest to the lowest OBS equal interval categories were 0.50 (0.38-0.66) for CRP, 0.50 (0.36-0.71) for WBC, and 0.75 (0.58-0.98) for LDL; all three p-values for trend <0.001. Gender modified the association between OBS and low HDL with significant inverse association observed only among women.
Although OBS was associated with cancer outcomes in previous studies, our results indicate that OBS does not play a role in prostate carcinogenesis. We found that OBS may be associated with some, but not all, biomarkers of inflammation and cardiovascular health. The associations of OBS with FIP and FOP were in the opposite directions; a finding that cannot be readily explained at this time.
Table of Contents
Chapter 1 Page 1
Corresponding Figures 1-3 and Tables 1-4...16
Chapter 2 Manuscripts 23
Oxidative Balance Score and the Risk of Incident Prostate Cancer in a Prospective U.S. Cohort Study...23
Corresponding Tables 1-5...39
Oxidative Balance Score and Oxidative Stress Biomarkers in a Study of Whites, African Americans, and African Immigrants...45
Corresponding Tables 1-9...61
Oxidative Stress, Inflammation, and Markers of Cardiovascular Health...70
Corresponding Tables 1-12...87
Chapter 3 Conclusions and Future Directions...110
About this Dissertation
|Committee Chair / Thesis Advisor|
|Oxidative Stress and Health Outcomes ()||2018-08-28||