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.