A Prospective Study of Plasma Total Cysteine and Risk of Breast Cancer
- Shumin M. Zhang123,
- Walter C. Willett234,
- Jacob Selhub5,
- JoAnn E. Manson123,
- Graham A. Colditz23 and
- Susan E. Hankinson23
- 1Division of Preventive Medicine and
- 2Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts; Departments of
- 3Epidemiology and
- 4Nutrition, Harvard School of Public Health, Boston, Massachusetts; and
- 5Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts
Abstract
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 32,826 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 B6, vitamin B12, 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.
Footnotes
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Grant support: Supported by research grants from the Breast Cancer Research Foundation and the Massachusetts Breast Cancer Research Grants Program and NIH Grants CA87969 and CA49449 and supported in part by the National Cancer Institute Specialized Program of Research Excellence (SPORE) in breast cancer at Brigham and Women’s Hospital and federal funds from the United States Department of Agriculture under agreement No. 58-1950-9-001.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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Requests for reprints: Shumin M. Zhang, Division of Preventive Medicine, Brigham and Women’s Hospital and Harvard Medical School, 900 Commonwealth Avenue East, Boston, Massachusetts 02215. Phone: (617) 278-0856; Fax: (617) 731-3843; E-mail: Shumin.Zhang{at}channing.harvard.edu
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↵6 The abbreviations used are: RR, relative risk; CI, confidence interval.
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- Accepted August 22, 1903.
- Received March 7, 1903.
- Revision received July 2, 1903.
