Journal of the National Cancer Institute Advance Access published online on June 10, 2008
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djn171
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© The Author 2008. Published by Oxford University Press.
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Urinary 6-Sulfatoxymelatonin Levels and Risk of Breast Cancer in Postmenopausal Women
Affiliations of authors: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (ESS); Department of Epidemiology, Harvard School of Public Health, Boston, MA (ESS); LBI-ACR and ACR-ITR VIEnna/CEADDP, Vienna, Austria (ESS); Department of Preventive and Predictive Medicine (FB, GS, EV, AC), Nutritional Epidemiology Unit (VK, S. Sieri), and Descriptive Epidemiology and Health Planning Unit (AM), Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale Tumori, Milan, Italy; Department of Social and Preventive Medicine, SPHHP, University at Buffalo (CTS, HJS); Molecular Chemoprevention Unit, Scientific Director Department (S. Strano), Istituto Nazionale Tumori Regina Elena IRCCS (HJS, PM), Rome, Italy; Department of Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada (HJS)
Correspondence to: Eva S. Schernhammer, MD, DrPH, Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Ave, Boston, MA 02115 (e-mail: eva.schernhammer{at}channing.harvard.edu).
Background: Low urinary melatonin levels have been associated with an increased risk of breast cancer in premenopausal women. However, the association between melatonin levels and breast cancer risk in postmenopausal women remains unclear.
Methods: We investigated the association between melatonin levels and breast cancer risk in postmenopausal women in a prospective case–control study nested in the Hormones and Diet in the Etiology of Breast Cancer Risk cohort, which included 3966 eligible postmenopausal women. The concentration of melatonin's major metabolite, 6-sulfatoxymelatonin, was measured in a baseline 12-hour overnight urine sample from 178 women who later developed incident breast cancer and from 710 matched control subjects. We used multivariable-adjusted conditional logistic regression models to investigate associations. Relative risks are reported as odds ratios (ORs). All statistical tests were two-sided.
Results: Increased melatonin levels were associated with a statistically significantly lower risk of invasive breast cancer in postmenopausal women (for women in the highest quartile of total overnight 6-sulfatoxymelatonin output vs the lowest quartile, multivariable OR also adjusted for testosterone = 0.56, 95% confidence interval [CI] = 0.33 to 0.97; Ptrend = .02). This association was strongest among never and past smokers (OR = 0.38, 95% CI = 0.20 to 0.74; Ptrend = .001) and after excluding women who were diagnosed with invasive breast cancer within 4 years after urine collection (OR = 0.34, 95% CI = 0.15 to 0.75; Ptrend = .002). We did not observe substantial variation in relative risks by hormone receptor status of breast tumors. Among the 3966 women in the cohort, 40 of the 992 women in the highest quartile of 6-sulfatoxymelatonin developed breast cancer during follow-up, compared with 56 of the 992 women in the lowest quartile of 6-sulfatoxymelatonin.
Conclusion: Results from this prospective study provide evidence for a statistically significant inverse association between melatonin levels, as measured in overnight morning urine, and invasive breast cancer risk in postmenopausal women.
| CONTEXT AND CAVEATS Prior knowledge Low levels of urinary melatonin have been associated with an increased risk of breast cancer in premenopausal women, but the risk in postmenopausal women remains unclear. Study design Prospective case–control study nested in the Hormones and Diet in the Etiology of Breast Cancer Risk cohort. Contribution Increased melatonin levels were associated with a statistically significantly lower risk of invasive breast cancer in postmenopausal women. Among the 992 women in the highest 6-sulfatoxymelatonin quartile, 40 developed breast cancer during follow-up, compared with 56 of the 992 women in the lowest 6-sulfatoxymelatonin quartile. Implications Further investigation into the primary mechanisms for the association between melatonin and breast cancer risk is warranted. Limitations Information on light exposure at night was lacking. The authors could not correct for errors in laboratory measurement of melatonin and within-person variability in melatonin measurements.
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Manuscript received February 4, 2008; revised April 2, 2008; accepted April 25, 2008.
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J Natl Cancer Inst 2008 100: 829.
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