title: Urinary excretion of melatonin and association with breast cancer: meta-analysis and review of the literature.
abstract: BACKGROUND
  Melatonin is an endocrine hormone secreted by the pineal gland during night hours that provides several biological functions in the circadian rhythm of humans. Due to anti-estrogenic properties, melatonin is considered to exhibit a protective role against the development of breast cancer (BC). Moreover, disruption of melatonin production through environmental influences, such as night work, is assumed to be a risk factor for BC.
  
  
  METHODS
  We reviewed recent findings concerning biological effects of melatonin on BC and conducted a meta-analysis to evaluate the association between melatonin and BC incidence. In random and fixed effects statistical models, concentrations (tertiles, quartiles) of the primary urinary metabolite of melatonin, 6-sulfatoxymelatonin (aMT6s), were tested for the assumption that women with the highest values would exhibit a lower risk of BC.
  
  
  RESULTS
  Statistical analysis of data from 5 prospective case-control studies indicates an inverse association between BC risk and the highest levels of urinary aMT6s. This effect seems to be influenced by lag intervals between aMT6s collection and the occurrence of BC, timing and methods of urine sampling, as well as genetic and environmental factors.
  
  
  CONCLUSIONS
  On the basis of the results of our meta-analysis, melatonin is likely to affect BC occurrence in women. However, methodological dissonances may require further studies.
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland ; Department of Gynecology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Michelle
authors.initials: M
authors.lastname: Basler
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Jetter
authors.affiliation: Department of Gynecology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Fink
authors.affiliation: Division of Biostatistics, Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Seifert
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Gerd A
authors.initials: GA
authors.lastname: Kullak-Ublick
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland ; Breast-Center Zürich and Onkozentrum Klinik im Park, Zurich, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Trojan
keywords: Breast cancer; Melatonin; Meta-analysis; Urinary excretion; aMT6s