Urinary Melatonin in Relation to Postmenopausal Breast Cancer Risk According to Melatonin 1 Receptor Status

Background: Urinary melatonin levels have been associated with a reduced risk of breast cancer in postmenopausal women, but this association might vary according to tumor melatonin 1 receptor (MT1R) expression.Methods: We conducted a nested case-control study among 1,354 postmenopausal women in the Nurses' Health Study, who were cancer free when they provided first-morning spot urine samples in 2000 to 2002; urine samples were assayed for 6-sulfatoxymelatonin (aMT6s, a major metabolite of melatonin). Five-hundred fifty-five of these women developed breast cancer before May 31, 2012, and were matched to 799 control subjects. In a subset of cases, immunohistochemistry was used to determine MT1R status of tumor tissue. We used multivariable-adjusted conditional logistic regression to estimate the relative risk (RR) of breast cancer [with 95% confidence intervals (CI)] across quartiles of creatinine-standardized urinary aMT6s level, including by MT1R subtype.Results: Higher urinary melatonin levels were suggestively associated with a lower overall risk of breast cancer (multivariable-adjusted RR = 0.78; 95% CI = 0.61-0.99, comparing quartile 4 vs. quartile 1; P_trend = 0.08); this association was similar for invasive vs. in situ tumors (P_{heterogeneity} = 0.12). There was no evidence that associations differed according to MT1R status of the tumor (e.g., P_{heterogeneity for overall breast cancer} = 0.88).Conclusions: Higher urinary melatonin levels were associated with reduced breast cancer risk in this cohort of postmenopausal women, and the association was not modified by MT1R subtype.Impact: Urinary melatonin levels appear to predict the risk of breast cancer in postmenopausal women. However, future research should evaluate these associations with longer-term follow-up and among premenopausal women. Cancer Epidemiol Biomarkers Prev; 26(3); 413-9. ©2016 AACR.