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Plasma Cysteinylglycine Levels and Breast Cancer Risk in Women

¹ Division of Preventive Medicine, ² Channing Laboratory, Department of Medicine, and ³ Department of Ambulatory Care and Prevention, Brigham and Women's Hospital and Harvard Medical School; ⁴ Department of Epidemiology, Harvard School of Public Health; and ⁵ Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts

Requests for reprints: Jennifer Lin, Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Avenue East, Boston, MA 02215. Phone: 617-278-0894; Fax: 617-232-3541; E-mail: jhlin{at}rics.bwh.harvard.edu.

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 (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. [Cancer Res 2007;67(23):11123–7]