It has been hypothesized that suppressed nocturnal
melatonin production is associated with an increased risk of
breast cancer, but results from several small prospective studies of the association have been inconclusive. We examined the association between nocturnal
melatonin and
breast cancer risk in a case-control study nested within the Guernsey III Study, a British prospective cohort study (1977-2009). Concentrations of
6-sulfatoxymelatonin were measured in prediagnostic first-morning urine samples from 251
breast cancer cases and 727 matched controls. Conditional logistic regression models were used to calculate odds ratios for
breast cancer in relation to
6-sulfatoxymelatonin level. No significant association was found between
6-sulfatoxymelatonin level and
breast cancer risk, either overall (for highest third vs. lowest, multivariable-adjusted odds ratio = 0.90, 95% confidence interval: 0.61, 1.33) or by menopausal status. However, in a meta-analysis of all published prospective data, including 1,113 cases from 5 studies, higher
6-sulfatoxymelatonin levels were associated with lower
breast cancer risk (for highest fourth vs. lowest, odds ratio = 0.81, 95% confidence interval: 0.66, 0.99). In summary, we found no evidence that
6-sulfatoxymelatonin level in a first-morning urine sample was associated with
breast cancer risk among British women. However, overall the published data suggest a modest inverse association between
melatonin levels and
breast cancer risk. Further data are needed to confirm this association.