A summary measure of pro- and anti-oxidant exposures and risk of incident, sporadic, colorectal adenomas

Abstract

Despite compelling basic science evidence, the search for causal associations linking specific pro- and anti-oxidants to presumably oxidative stress-related neoplasms, such as colorectal adenoma, has produced inconsistent results. We developed an oxidative balance score (OBS) to characterize the pro-oxidant and anti-oxidant exposures of 2,305 participants in a case-control study of colorectal adenoma that used both endoscopy-confirmed and community controls. Twelve lifestyle medical and dietary factors with known pro- or anti-oxidant properties were considered. Each high anti-oxidant exposure and low pro-oxidant exposure was awarded one or two points depending on the level of exposure, and the points for each OBS component were summed. We observed a significant inverse association between OBS (continuous variable) and colorectal adenoma in the analyses with either community, or endoscopy controls (each p-trend < 0.01). When the OBS was treated as an ordinal variable and a score of <or=3 points was used as the referent category, in the analyses with the endoscopy controls the adjusted odds ratios for scores of 4-6, 7-9, 10-12, 13-15, and 16+, were 0.42, 0.32, 0.22, 0.20, and 0.19, respectively, with all 95% confidence intervals excluding 1.0. The corresponding analysis for community controls showed a similar trend. Our findings are in line with the basic science evidence supporting the role of oxidative stress in colorectal neoplasia.

DNA Damage Is a Potential Marker for TP53 Mutation in Colorectal Carcinogenesis

“…A direct proportion between oxidative DNA damage in normal and tumor tissues, with a significant increase in tumor lesions were found in this study. These results are in agreement with previous findings in literature, showing higher oxidative DNA damage in the neoplastic tissues when compared to normal tissues [1,3,5,6,19,22,23,26,29]. Similarly, two times higher levels of 8-OHdG have been reported in the tumor tissues of CRC patients when compared with normal tissues [22].…”

“…Leung et al also demonstrated that in CRC, oxidative stress increases during the progression of liver metastases from resectable to unresectable lesions, as observed by depletion of antioxidant vitamins and increased lipid peroxidation [30]. Oxidative DNA damage increases from normal tissues to adenoma and furthermore from adenoma to adenocarcinoma, in agreement with existing literature [1,5,6,19,22,23,29]. Mucosal exposure to ROS promotes oxidative DNA damage in colonic cells.…”

“…The close relationship between chronic inflammatory bowel disease and CRC [4][5][6] as well as between ROS, gastritis, and gastric cancer [12] support the hypothesis that chronic inflammation may be the initial event in carcinogenesis [17,28,30]. Researchers have previously demonstrated an association between oxidative imbalance and colorectal adenoma [1,29]. Leung et al also demonstrated that in CRC, oxidative stress increases during the progression of liver metastases from resectable to unresectable lesions, as observed by depletion of antioxidant vitamins and increased lipid peroxidation [30].…”

Antioxidant Micronutrients and Biomarkers of Oxidative Stress and Inflammation in Colorectal Adenoma Patients: Results from a Randomized, Controlled Clinical Trial

“…Diets high in fruits, vegetables, and antioxidants have been associated with a lower risk of cancer (11), especially colorectal cancer (29)(30)(31). In addition, colorectal epithelial cell proliferation, a potential biomarker of risk for colorectal cancer, was reduced by several antioxidant micronutrients, such as vitamins A, C, and E and β-carotene (12,32,33).…”

Oxidative balance score and oxidative stress biomarkers in a study of Whites, African Americans, and African immigrants

“…Previous studies found that a higher OBS was associated with lower risk of colorectal adenoma (Goodman et al, 2008; Trichopoulou et al, 1995), colorectal cancer (Dash, 2010), and mortality (Van Hoydonck et al, 2002). By contrast, an OBS was not associated with prostate cancer risk (Agalliu et al, 2011), indicating that the role of oxidative stress in human chronic disease pathophysiology may be organ or disease specific.…”