A prospective study of plasma total cysteine and risk of breast cancer.

Cysteine is the precursor of glutathione, a powerful intracellular antioxidant and an important detoxifying agent of carcinogens. However, data relating plasma total cysteine to breast cancer risk are sparse. We conducted a prospective nested case-control study among 32826 women in the Nurses' Health Study who provided blood specimens during 1989-1990. Through 1996, a total of 712 incident breast cancer cases were identified and individually matched to 712 controls by year of birth, time of day that blood was drawn, fasting status, month of blood sampling, recent use of postmenopausal hormones at the time of blood collection, and menopausal status. Conditional logistic regression with adjustment for other risk factors for breast cancer was used to estimate the relative risks and 95% confidence intervals of breast cancer by levels of plasma total cysteine. Higher plasma total cysteine concentrations were significantly associated with a lower risk of breast cancer. For women in the highest quintile of plasma total cysteine, compared with those in the lowest quintile, the multivariate relative risk was 0.44 (95% confidence interval, 0.26-0.74). This association was dose dependent (P for trend = 0.002) and independent of plasma measures of folate, vitamin B(6), vitamin B(12), and total homocysteine. The inverse association between plasma total cysteine concentrations and risk of breast cancer was not significantly modified by other risk factors for breast cancer, except that a stronger association was observed among women who were leaner. The findings from this prospective study suggest that higher plasma concentrations of total cysteine predict a reduced risk of breast cancer. Cysteine or its precursors might have the potential to be chemopreventive against breast cancer.