Biomarkers of Oxidative Stress and Risk of Developing Colorectal Cancer: A Cohort-nested Case-Control Study in the European Prospective Investigation Into Cancer and Nutrition

Abstract

Oxidative stress has been shown to play an important role in carcinogenesis, but prospective evidence for an association between biomarkers of oxidative stress and colorectal cancer (CRC) risk is limited. The authors investigated the association between prediagnostic serum levels of oxidative stress indicators (i.e., reactive oxygen metabolites (ROM) and ferric reducing ability of plasma (FRAP)) and CRC risk. This was examined in a nested case-control study (1,064 CRC cases, 1,064 matched controls) in the European Prospective Investigation Into Cancer and Nutrition cohort (1992-2003). Incidence rate ratios and 95% confidence intervals were calculated using conditional logistic regression analyses. ROM were associated with overall CRC risk (highest tertile vs. lowest: adjusted incidence rate ratio (IRR adj) ¼ 1.91, 95% confidence interval (CI): 1.47, 2.48), proximal (IRR adj ¼ 1.89, 95% CI: 1.06, 3.36) and distal (IRR adj ¼ 2.31, 95% CI: 1.37, 3.89) colon cancer, and rectal cancer (IRR adj ¼ 1.69, 95% CI: 1.05, 2.72). When results were stratified by tertile of follow-up time, the association remained significant only in participants with less than 2.63 years of follow-up (IRR adj ¼ 2.28, 95% CI: 1.78, 2.94; P-heterogeneity < 0.01). FRAP was not associated with CRC risk. In conclusion, prediagnostic serum ROM levels were associated with increased risk of CRC. However, this association was seen only in subjects with relatively short follow-up, suggesting that the association results from production of reactive oxygen species by preclinical tumors. biological markers; case-control studies; colorectal neoplasms; oxidative stress Abbreviations: CI, confidence interval; CRC, colorectal cancer; FRAP, ferric reducing ability of plasma; ICD-10, International Classification of Diseases, Tenth Revision; IRR, incidence rate ratio; ROM, reactive oxygen metabolites; ROS, reactive oxygen species. Worldwide, colorectal cancer (CRC) is the third most common cancer, accounting for approximately 1.2 million new cases and 608,000 deaths per year (1). Several endogenous factors, as well as lifestyle and dietary factors, related to CRC risk have been identified (2). A diet rich in fruit and vegetables and containing antioxidants in abundance has been shown to be associated with a lower risk of cancer, including CRC (3, 4). Moreover, oxidative

Plasma and dietary carotenoids and vitamins A, C and E and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition

“…This likely indicates a certain degree of reverse causality, possibly caused by the oxidative stress induced by the subclinical cancer as was suggested in the association between ROM and CRC previously within EPIC. 32,36 The associations of dietary b-carotene and vitamins C and E were not ratified by their plasma counterparts. The inconsistency in associations between dietary and plasma measures may exist because biomarkers seem to better reflect internal dose than questionnaire data, which may correlate stronger with lifestyle factors and the intake of other components derived from the dietary questionnaire related to fruit and vegetable consumption.…”

“…Stratification of the observed associations by geographical region [Scandinavia (Denmark, Norway, Sweden), Central Europe (France, Germany, Netherlands and UK) and Mediterranean (Greece, Italy, Spain)] was performed to determine whether associations were consistent throughout these regions. Additionally, in case-control sets with reactive oxygen metabolites (ROMs) concentration available (488 colon and 290 rectum case-control sets) from a previous study within the EPIC study, 32 observed associations were additionally adjusted for ROM status to examine whether the association could be explained by their antioxidant properties.…”

The Role of Biomarkers of Oxidative Stress in Breast Cancer Risk and Prognosis: A Systematic Review of the Epidemiologic Literature

“…9,13 While nested case-control studies can help minimize this limitation, the concern that oxidative stress may be generated by the preclinical tumor remains. 32 This potential bias can be evaluated by stratifying associations by length of follow-up time, which was rarely done in the identified reports. Another limitation is that breast cancer has been shown to be an etiologically heterogeneous disease, with studies showing modification of known associations by tumor subtype.…”

“…20,28 Biomarkers of oxidative stress have been investigated for their association with the development and progression of several cancer types, and in particular breast cancer, as oxidative stress mechanisms may be involved in several known breast cancer risk factors, including obesity and daily alcohol intake, and circulating estrogen levels. [29][30][31][32][33][34] Breast cancer cells have been shown to be susceptible to oxidative damage and have high levels of oxidative stress, including protein damage, DNA damage, and lipid peroxidation. 9,35 Furthermore, several breast cancer risk factors may alter levels of endogenous oxidative stress.…”

Short-Term Stability of Biomarkers of Oxidative Stress and Antioxidant Status in Human Serum

“…A faster and cheaper way for the determination of the total antioxidant capacity is to perform only one assay in which all components contribute to an integrating value [2][3][4]. The biomarkers of oxidative stress and antioxidant status are important to assess a physiologically altered state [5], to detect adverse nutritional habits [6] or an increased disease state [7,8].…”