The Reduction in Circulating Melatonin Level May Contribute to the Pathogenesis of Ovarian Cancer: A Retrospective Study

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 Abstract
Ovarian cancer is the third most common gynaecological malignancy. Changes in circadian rhythms such as bright light exposure may affect female reproductive physiology. Night shift work is associated with higher risks of developing gynaecological cancers. In addition, the season of birth is also suggested as an important environmental risk factor for developing gynaecological cancers. Melatonin may play an important role in this association as a marker of circadian rhythms. Serum from 96 women with ovarian cancer and 40 healthy women were collected and the level of melatonin was measured. In addition 277 women with ovarian cancer and 1076 controls were retrospectively collected for season of birth analysis over seven years. The serum levels of melatonin were significantly lower in women with ovarian cancer compared with healthy women (p<0.05). However there was no difference in melatonin levels in perimenopausal and postmenopausal patients. In addition, there is no statistically significant difference in seasonal distribution of birth between ovarian cancer patients and the control group. The melatonin levels in ovarian cancer patients and controls were not associated with the season of birth. Our results demonstrate the lower serum levels of melatonin in ovarian cancer patients which may contribute to the pathogenesis of ovarian cancer. The incidence of ovarian cancer was not associated with the season of birth. The serum levels of melatonin do not appear to be associated with season of birth in ovarian cancer patients.

Introduction

Ovarian cancer is the third most common gynaecological malignancy and the leading cause of death in gynaecological cancers globally and the incidence has been increasing in the last decade [1]. Although the pathogenesis of the ovarian cancer is unclear, studies have suggested that changes in circadian rhythms such as bright light exposure may affect female reproductive physiology [2]. Night shift work is associated with higher risks of developing breast [3-5] and endometrial cancer [6]. Other studies also suggested that the season of birth may be an important environmental risk factor for developing endometrial cancer [7]. However, the mechanism of this association and whether season of birth is also associated with developing ovarian cancer remain unknown.
One of the speculations for this association is the reduction in production of melatonin by pineal glands. Melatonin a marker of circadian rhythms is an endogenously-produced lipid soluble hormone whose level changes with circadian rhythm. It has been proposed that melatonin is synthesized in mitochondria at high levels [8] and has multifaceted functions, including direct free radical scavenging. In addition to pineal gland, melatonin is also produced by the ovaries, regulating the function of the ovaries [9, 10]......

 In conclusion, we demonstrate a reduction of melatonin levels in women with ovarian cancer at diagnosis. There is no association between the incidence of ovarian cancer and season of birth, and melatonin level in women with ovarian cancer at diagnosis is not subject to season of birth. Future prospective studies are needed to confirm our findings in this study.