• Ruth C Travis, Diane S Allen, Ian S Fentiman, and Timothy J Key.
• Cancer Research UK, Epidemiology Unit, University of Oxford, Oxford, UK. ruth.travis@cancer.org.uk
• J. Natl. Cancer Inst. 2004 Mar 17; 96 (6): 475-82.

BackgroundExperimental data from animals suggest a protective role for the pineal hormone melatonin in the etiology of breast cancer, but results from the few retrospective case-control studies that examined the association in humans have been inconsistent. To determine whether low levels of endogenous melatonin are associated with an increased risk for developing breast cancer, we conducted a prospective nested case-control study among British women.MethodsConcentrations of 6-sulfatoxymelatonin, the main metabolite of melatonin in urine and a validated marker of circulating melatonin levels, were measured by radioimmunoassay in 24-hour urine samples collected from women shortly after enrollment in the prospective Guernsey III Study. Levels of 6-sulfatoxymelatonin were compared among 127 patients diagnosed with breast cancer during follow-up and among 353 control subjects, matched for age, recruitment date, menopausal status, and day of menstrual cycle for premenopausal women or number of years postmenopausal for postmenopausal women. Associations were examined by analyses of covariance and conditional logistic regression. All tests of statistical significance were two-sided.ResultsNo statistically significant differences in urinary 6-sulfatoxymelatonin concentrations were observed between women who developed breast cancer and control subjects among premenopausal or postmenopausal women (P=.8 and P=.9, respectively). When data from premenopausal and postmenopausal women were combined in a multivariable analysis adjusted for potential confounders and grouped into three categories defined by 6-sulfatoxymelatonin tertiles of control subjects, the level of 6-sulfatoxymelatonin excreted was not statistically significantly associated with the risk of breast cancer (odds ratio [OR] for breast cancer = 0.95, 95% confidence interval [CI] = 0.55 to 1.65, comparing the middle category with the lowest category of 6-sulfatoxymelatonin concentration, and OR = 0.99, 95% CI = 0.58 to 1.70, comparing the highest category with the lowest category).ConclusionWe found no evidence that the level of melatonin is strongly associated with the risk for breast cancer.

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