Low urinary levels of melatonin are associated with an increased risk of advanced prostate cancer (PCa), new findings suggest.

In a prospective study, researchers measured first morning void urinary levels of 6-sulfatoxymelatonin (6-STM), the primary melatonin metabolite, in a cohort of 928 Icelandic men who did not have PCa. During the study period, 111 men were diagnosed with PCa, including 24 with advanced disease.  Men with morning 6-STM levels below the median had a significant 4-fold increased risk for advanced PCa compared with men with levels above the median, according to findings published online ahead of print in European Urology. The median follow-up time from urine collection to PCa diagnosis was 2.3 years.

Men who reported sleep problems at baseline had lower morning 6-STM levels compared with those who reported no sleep problems.

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“The study adds to accumulating epidemiologic data investigating associations between circadian disruption or sleep loss and PCa, and provides a potential mechanism and framework for understanding prior results,” the authors noted.

The researchers, led by Sarah C. Markt, ScD, of the Harvard School of Public Health in Boston, noted that the International Agency for Research on Cancer categorized night-shift work as a probable human carcinogen based primarily on breast cancer data. Night-shift work disrupts circadian rhythms and suppresses melatonin secretion through nocturnal exposure to artificial light, they explained. Previous studies have demonstrated that night-shift work is associated with an increased risk of PCa and elevated PSA among men without PCa.

For example, a study by Marie-Élise Parent, PhD, of INRS-Institut Armand-Frappier, a component of the University of Quebec in Laval, found that men who had ever worked at night had a 2.8 times increased PCa risk compared with men who never worked at night, after adjusting for potential confounders.

The study, published in the American Journal of Epidemiology (2012;176:751-759), examined data from a population-based, case-control study conducted in Montreal that elicited information about job histories—including work hours—from 3,137 men with various incident cancers and 512 controls.

Dr. Markt’s group acknowledged some study limitations. Their study results rest on a single morning urinary 6-STM measurement, which may not represent long-term levels, they noted. Other limitations included the small number of cases of advanced PCa that were diagnosed and a short follow-up.

Additionally, men may have had underlying disease at the time of exposure assessment and the study was restricted to elderly men in Iceland. Melatonin levels in this population may differ from those of other populations. Despite the study’s limitations, the researchers said “it is unlikely that underlying biologic impact on PCa pathogenesis would differ.”

The men in the study were participants in the Age, Gene/Environment Susceptibility-Reykjavik study, which collected information by physical examination, questionnaire, and biologic specimens during a 2-day assessment from 2002 to 2006. PCa diagnoses and causes of death were ascertained by linkage with the Icelandic Cancer Registry and Statistics Iceland, the main official institute providing statistics on the country.

The researchers defined advanced PCa as extraprostatic stage T3a or higher, N1/M1, or death from PCa).