Urinary melatonin levels, sleep disruption, and risk of prostate cancer in elderly men

Lara G Sigurdardottir¹, Sarah C Markt², Jennifer R Rider³, Sebastien Haneuse⁴, Katja Fall⁵, Eva S Schernhammer³, Rulla M Tamimi³, Erin Flynn-Evans⁶, Julie L Batista³, Lenore Launer⁷, Tamara Harris⁷, Thor Aspelund⁸, Meir J Stampfer³, Vilmundur Gudnason⁹, Charles A Czeisler⁶, Steven W Lockley⁶, Unnur A Valdimarsdottir¹⁰, Lorelei A Mucci¹¹

Affiliations

¹ Centre of Public Health Sciences, University of Iceland, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland; The Icelandic Cancer Society, Reykjavik, Iceland.
² Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. Electronic address: sec110@mail.harvard.edu.
³ Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁴ Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA.
⁵ Centre of Public Health Sciences, University of Iceland, Reykjavik, Iceland; Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Clinical Epidemiology Unit, Örebro University and Örebro University Hospital, Örebro, Sweden.
⁶ Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA; Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA, USA.
⁷ Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD, USA.
⁸ Centre of Public Health Sciences, University of Iceland, Reykjavik, Iceland; Icelandic Heart Association, Kopavogur, Iceland.
⁹ Faculty of Medicine, University of Iceland, Reykjavik, Iceland; Icelandic Heart Association, Kopavogur, Iceland.
¹⁰ Centre of Public Health Sciences, University of Iceland, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland; Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
¹¹ Centre of Public Health Sciences, University of Iceland, Reykjavik, Iceland; Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

PMID: 25107635
PMCID: PMC4318783
DOI: 10.1016/j.eururo.2014.07.008

Urinary melatonin levels, sleep disruption, and risk of prostate cancer in elderly men

Lara G Sigurdardottir et al. Eur Urol. 2015 Feb.

. 2015 Feb;67(2):191-4.

doi: 10.1016/j.eururo.2014.07.008. Epub 2014 Aug 5.

Authors

Affiliations

¹ Centre of Public Health Sciences, University of Iceland, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland; The Icelandic Cancer Society, Reykjavik, Iceland.
² Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. Electronic address: sec110@mail.harvard.edu.
³ Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁴ Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA.
⁵ Centre of Public Health Sciences, University of Iceland, Reykjavik, Iceland; Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Clinical Epidemiology Unit, Örebro University and Örebro University Hospital, Örebro, Sweden.
⁶ Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA; Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA, USA.
⁷ Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD, USA.
⁸ Centre of Public Health Sciences, University of Iceland, Reykjavik, Iceland; Icelandic Heart Association, Kopavogur, Iceland.
⁹ Faculty of Medicine, University of Iceland, Reykjavik, Iceland; Icelandic Heart Association, Kopavogur, Iceland.
¹⁰ Centre of Public Health Sciences, University of Iceland, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland; Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
¹¹ Centre of Public Health Sciences, University of Iceland, Reykjavik, Iceland; Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

PMID: 25107635
PMCID: PMC4318783
DOI: 10.1016/j.eururo.2014.07.008

Abstract

Melatonin has anticarcinogenic properties in experimental models. We undertook a case-cohort study of 928 Icelandic men without prostate cancer (PCa) nested within the Age, Gene/Environment Susceptibility (AGES)-Reykjavik cohort to investigate the prospective association between first morning-void urinary 6-sulfatoxymelatonin (aMT6s) levels and the subsequent risk for PCa, under the hypothesis that men with lower aMT6s levels have an increased risk for advanced PCa. We used weighted Cox proportional hazards models to assess the association between first morning-void aMT6s levels and PCa risk, adjusting for potential confounders. A total of 111 men were diagnosed with incident PCa, including 24 with advanced disease. Men who reported sleep problems at baseline had lower morning aMT6s levels compared with those who reported no sleep problems. Men with morning aMT6s levels below the median had a fourfold statistically significant increased risk for advanced disease compared with men with levels above the median (hazard ratio: 4.04; 95% confidence interval, 1.26-12.98). These results require replication in larger prospective studies with longer follow-up.

Patient summary: In this report, we evaluated the prospective association between urinary aMT6s levels and risk of PCa in an Icelandic population. We found that lower levels of aMT6s were associated with an increased risk for advanced PCa.

Keywords: Circadian rhythm; Melatonin levels; Prostate cancer.

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Figures

**Fig. 1**
Percent of people in each sleep disruption category with low 6-sulfatoxymelatonin (6-STM) levels in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik case–cohort study. *In men without sleep problems (n = 309), the distribution of 6-STM was as follows: mean = 22.0 ng/ml, median = 18.8 ng/ml, 25th percentile = 11.1 ng/ml, and 10th percentile = 6.5 ng/ml. **Low 6-STM: 6-STM levels below the 25th percentile in men without sleep problems (11.1 ng/ml). † Number of men with low 6-STM levels (ie, <11.1 ng/ml).

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Comment in

Melatonin, sleep, and prostate cancer in elderly men: study, hypothesis development, and icelandic options.
Erren TC, Slanger TE, Groß JV, Reiter RJ. Erren TC, et al. Eur Urol. 2015 Feb;67(2):195-7. doi: 10.1016/j.eururo.2014.09.033. Epub 2014 Oct 1. Eur Urol. 2015. PMID: 25282366 No abstract available.

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Urinary melatonin levels, sleep disruption, and risk of prostate cancer in elderly men

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Urinary melatonin levels, sleep disruption, and risk of prostate cancer in elderly men

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