28151704

PMC5336486

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 2000–2002; 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).

Conclusion

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.

CDC Public Access

P01 CA087969/CA/NCI NIH HHS/United States
R01 OH009803/OH/NIOSH CDC HHS/United States
UM1 CA186107/CA/NCI NIH HHS/United States