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Higher urinary melatonin levels had a significant inverse association with risk of aggressive prostate cancer, data from a cohort study showed.
Men with the higher levels of 6-sulfatoxymelatonin had a 75% lower risk of aggressive prostate cancer than men who had levels below the median.
Urinary melatonin had a near-significant association with overall prostate cancer risk, Sarah Markt, MPH, of the Harvard School of Public Health, reported at the Conference on Advances in Prostate Cancer Research in San Diego, which was co-sponsored by the American Association for Cancer Research and the Prostate Cancer Foundation.
"These are preliminary, unpublished results that definitely require replication in further prospective studies, but the findings do provide support for the public health implication of maintaining a stable light-dark and sleep-wake cycle," Markt told MedPage Today. "Because melatonin levels are potentially modifiable, further studies of melatonin and prostate cancer risk and progression are warranted."
Melatonin is a key hormonal output of circadian rhythm and may influence the output or production of other hormones. Circadian rhythm affects a number of biological processes but is perhaps best known for its influence on sleep and wakefulness.
Some evidence has suggested that melatonin's hormonal influences extend to certain types of cancer, including breast and prostate cancer. In prostate cancer cell lines, for example, melatonin has demonstrated activity consistent with chemopreventive effects, including inhibition of proliferation, promotion of apoptosis, and arrest of cell-cycle progression, said Markt.
Additional supporting evidence has come from epidemiologic studies in other types of cancer. As an example, higher levels of 6-sulfatoxymelatonin are associated with a lower risk of breast cancer.
However, no studies had prospectively examined the relationship between melatonin levels and prostate cancer risk.
Markt and colleagues analyzed data on 928 men enrolled in the Age, Genes/Susceptibility (AGES)-Reykjavik cohort in Iceland. Participants provided first-morning voided urine samples for ascertainment of baseline 6-sulfatoxymelatonin levels.
Altogether, the cohort had a median 6-sulfatoxymelatonin level of 17.14 ng/mL. The investigators found that almost 15% of the AGES-Reykjavik cohort reported trouble falling asleep, 20% reported difficulty staying asleep, and almost a third reported using sleep medications.
Men who reported any sleep-related problems (including use of sleep medications) had significantly lower levels of the melatonin metabolite.
The men were followed for 3 to 7 years, during which time 111 participants had new prostate cancer diagnoses, including 24 cases of advanced disease at diagnosis.
Men with 6-sulfatoxymelatonin levels higher than the median value had a 31% lower risk of developing prostate cancer compared with men who had levels lower than the median, but the difference did not achieve statistical significance (HR 0.69, 95% CI 0.44-1.08).
Higher-than-median levels of 6-sulfatoxymelatonin were associated with a 75% reduction in the risk of aggressive prostate cancer as compared with lower levels, a difference that did reach statistical significance (HR 0.25, 95% CI 0.08-0.80).
"We think there are three possibly inter-related pathways by which circadian disruption could be associated with prostate cancer," said Markt. "One is through disrupted melatonin, one is through disrupted sleep, and the last is through disruption in the circadian rhythm itself, due to light exposure."
Explanations other than those cited by Markt also could be plausible, said William Nelson, MD, of Johns Hopkins.
"The mechanism could be through melatonin action on its receptors, through its anti-oxidant properties, or through indirect effects on the immune system and other host physiology," Nelson, co-chair of the conference program committee said in an email. "Further study will be needed to elucidate the mode by which melatonin affects prostate cancer progression."
The findings are provocative, even though they did not come from a clinical trial of melatonin and require validation.
"Men threatened by prostate cancer could be counseled to allot enough time for healthy, restful, sleep," said Nelson.
Markt and colleagues reported no relevant disclosures.
- Reviewed by F. Perry Wilson, MD, MSCE Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner
AACR-Prostate Cancer Foundation Conference on Advances in Prostate Cancer ResearchSource Reference: Markt SC, et al "Urinary melatonin levels, sleep disruption, and risk of prostate cancer" Prostate Cancer Res 2014 Abstract 270322_1.