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;Ptrend= 0.08); this association was similar for invasive vs.in situtumors (Pheterogeneity= 0.12). There was no evidence that associations differed according to MT1R status of the tumor (e.g.,Pheterogeneity 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.
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. nheed@channing.harvard.edu.
Elizabeth E
EE
Devore
Clinical Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts.
Erica T
ET
Warner
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
A Heather
AH
Eliassen
Division of Biostatistics and Epidemiology, University of Massachusetts Amherst, Amherst, Massachusetts.
Susan B
SB
Brown
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
Andrew H
AH
Beck
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.|Division of Biostatistics and Epidemiology, University of Massachusetts Amherst, Amherst, Massachusetts.
Susan E
SE
Hankinson
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.|Department of Epidemiology, Center for Public Health, Medical University of Vienna, Vienna, Austria.
Eva S
ES
Schernhammer
D000368:Aged; D014408:Biomarkers, Tumor / Q000652:urine*; D001943:Breast Neoplasms / Q000737:chemistry / Q000453:epidemiology / Q000652:urine*; D016022:Case-Control Studies; D003401:Creatine / Q000652:urine; D005260:Female; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008137:Longitudinal Studies; D008550:Melatonin / Q000652:urine*; D008875:Middle Aged; D017698:Postmenopause / Q000652:urine; D044122:Receptor, Melatonin, MT1 / Q000032:analysis*; D012307:Risk Factors
D014408:Biomarkers, Tumor; D044122:Receptor, Melatonin, MT1; D008550:Melatonin; D003401:Creatine