Abstract
A40
Background: Cysteinylglycine (CysGly), a prooxidant and generated during the catabolism of glutathione (GSH), has been suggested to induce oxidative stress and lipid peroxidation, leading to the development of human cancers. Observational data relating CysGly status to breast cancer risk are lacking. >Methods: We prospectively evaluated plasma CysGly levels and invasive breast cancer risk in the Women’s Health Study (WHS), a completed randomized trial evaluating low-dose aspirin and vitamin E for the primary prevention of cancer and cardiovascular disease among women aged >= 45 years and free of cancer and cardiovascular disease at the time of enrollment beginning in 1992. Blood samples were collected at baseline from 28,345 women. We included, in the analysis, 812 incident cases of invasive breast cancer identified as of 2004 and 812 individually matched control subjects. We additionally evaluated the effect modification by risk factors for oxidative stress such as randomized vitamin E treatment assignment (600 IU administered every other day, placebo), alcohol consumption (less or greater than 9 gm/day, 75th percentile among drinkers), and obesity (less or greater than 25 kg/m2). Logistic regression controlling for matching factors as well as other risk factors for breast cancer was used to estimate relative risks (RRs) and 95% confidence intervals (CIs). Tests for multiplicative interactions between CysGly levels and modifiers were performed by entering each product term into the multivariate model. All statistical tests were two-sided. >Results: We observed no overall association between plasma CysGly and invasive breast cancer risk. However, higher CysGly levels were marginally associated with an increased risk of breast cancer in several high oxidative-stress groups. Women in the higher 4 quintile groups of CysGly relative to the lowest group had multivariate RRs (95% CIs) of 1.44 (0.87-2.39), 0.89 (0.54-1.47), 1.57 (0.95-2.61), and 1.64 (1.01-2.66) in the vitamin E placebo group (p for trend=0.04), of 1.91 (0.75-4.89), 1.48 (0.59-3.73), 1.75 (0.65-4.74), and 2.51 (1.01-6.24) in the high alcohol intake group (p for trend=0.07), and of 1.08 (0.61-1.89), 1.19 (0.67-2.12), 1.38 (0.77-2.47), and 1.66 (0.97-2.84) in the overweight and obese group (p for trend=0.03). >Conclusions: Our findings suggest that higher CysGly levels, a prooxidant produced by the catabolism of GSH, may predict an increased risk for developing breast cancer among women exposed to peroxidation-prone environments such as high alcohol consumption, low antioxidant intake, or excess weight.
Sixth AACR International Conference on Frontiers in Cancer Prevention Research-- Dec 5-8, 2007; Philadelphia, PA