cysteinylglycine and Obesity

Cysteinylglycine, a prooxidant generated during the catabolism of glutathione, has been suggested to induce oxidative stress and lipid peroxidation, leading to the development of human cancers. Observational data relating cysteinylglycine status to breast cancer risk are lacking. We prospectively evaluated plasma cysteinylglycine levels and invasive breast cancer risk among 812 case-control pairs nested in the Women's Health Study, a completed randomized trial evaluating low-dose aspirin and vitamin E in middle-aged and older women. We additionally evaluated the effect modification by risk factors for oxidative stress, such as vitamin E assignment, alcohol consumption, obesity, and postmenopausal hormone use. Logistic regression controlling for matching factors, as well as other risk factors for breast cancer, was used to estimate relative risks (RR) and 95% confidence intervals (95% CI). All statistical tests were two sided. We observed no overall association between plasma cysteinylglycine and invasive breast cancer risk. However, higher cysteinylglycine levels were marginally associated with an increased risk of breast cancer in the high oxidative stress groups. Women in the highest quintile group of cysteinylglycine relative to the lowest group had multivariate RRs (95% CIs) of 1.64 (1.01-2.66; P(trend) = 0.04) in the vitamin E placebo group, 2.51 (1.01-6.24; P(trend) = 0.07) in the high alcohol intake group (>or=9 g/day), and 1.66 (0.97-2.84; P(trend) = 0.03) in the overweight and obese group. Our findings suggest that women who are susceptible to experiencing oxidative stress may be at a greater risk for developing breast cancer.

Topics: Alcohol Drinking; Breast Neoplasms; Carcinoma, Ductal, Breast; Case-Control Studies; Dipeptides; Female; Humans; Middle Aged; Obesity; Oxidative Stress; Peptide Fragments; Postmenopause; Prospective Studies; Receptors, Antigen, T-Cell; Risk Factors; Vitamin E

We hypothesized that redox analysis could provide sensitive markers of the oxidative pathway associated to the presence of an increasing number of cardiovascular risk factors (RFs), independently of type. We classified 304 subjects without cardiovascular disease into 4 groups according to the total number of RFs (smoking, hypertension, hypercholesterolaemia, hyperhomocysteinaemia, diabetes, obesity, and their combination). Oxidative stress was evaluated by measuring plasma total and reduced homocysteine, cysteine (Cys), glutathione, cysteinylglycine, blood reduced glutathione, and malondialdehyde. Twenty-seven percent of subjects were in group 0 RF, 26% in 1 RF, 31% in 2 RF, and 16% in ≥ 3 RF. By multivariable ordinal regression analysis, plasma total Cys was associated to a higher number of RF (OR = 1.068; 95% CI = 1.027-1.110, P = 0.002). Total RF burden is associated with increased total Cys levels. These findings support a prooxidant effect of Cys in conjunction with RF burden, and shed light on the pathophysiologic role of redox state unbalance in preclinical atherosclerosis.

Topics: Adult; Analysis of Variance; Cardiovascular Diseases; Cysteine; Diabetes Complications; Dipeptides; Female; Glutathione; Humans; Hypercholesterolemia; Hyperhomocysteinemia; Hypertension; Logistic Models; Male; Malondialdehyde; Middle Aged; Obesity; Oxidation-Reduction; Oxidative Stress; Prospective Studies; Risk Assessment; Risk Factors; Smoking