Are some melanomas caused by artificial light?
Introduction
Cutaneous melanoma is a potentially lethal neoplasm with an incidence rate that has been increasing considerably worldwide in white-skinned populations over the past decades [1]. This incidence rate has risen more rapidly than that of any other cancer, with several authors referring to these trends as the “melanoma epidemic” [2]. Several risk factors for melanoma have been clearly established, such as exposure to ultraviolet radiation (UVR) [3]; phenotypic factors such as naevus count, freckling, and phototype; and familial history of the disease [4], [5]. However, these factors altogether may not wholly explain the epidemiological trends observed for this cancer, and it is essential to determine which other aspects may also play a role in the melanoma burden.
Melatonin is a pineal hormone with circadian production rhythm: secretion is maximal in the dark, and is inhibited by retinal exposure to light [6]. After its discovery by Lerner et al. in 1958 [7], melatonin has been shown to be involved in several biological processes, such as circadian and seasonal biorhythms, and sleep initiation. More recently, it has been shown that melatonin is also synthesized and metabolized locally at extrapineal sites, such as the skin [8]. Melatonin has also proven an efficient antioxidant and anti-carcinogenic agent in experimental studies; in the skin, this hormone was shown to exhibit anti-tumour and growth-suppressive effects, and to effectively reduce damage from exposure to UVR [8], [9], [10].
In 1978, Cohen et al. postulated that reduced function of the pineal gland might lead to the development of breast cancer, mainly on the grounds that, because of the inhibitory effect of melatonin on oestrogens, melatonin suppression could lead to increased oestrogen production and thus increased breast cancer [11].
Later, in 1987, Stevens proposed the Light-At-Night (LAN) theory, which postulates that the increasing use of artificial light-at-night, paralleling industrialization, may explain a part of the increasing breast cancer incidence by inhibiting melatonin secretion [12]. Suggestive evidence has then consistently accumulated in favour of this hypothesis: several studies reported a positive association between night-shift work and breast cancer risk; totally blind women have been shown to be at increased risk for breast cancer compared to normally sighted women; a modest inverse association has been reported between sleep duration and breast cancer risk; an increased breast cancer risk was reported in relation to increased bedroom light level at night; indigenous populations living at extreme northern latitudes were generally shown to be at decreased breast cancer risk; breast cancer incidence has been shown to be higher in communities with higher levels of night-time lighting; and rodent models confirmed anti-tumorigenic effects of melatonin, and its inhibition by exposure to light [13]. Recently, higher urinary melatonin levels were found to be associated with a lower risk of breast cancer in postmenopausal women [14], and particular clock genes polymorphisms were associated with breast cancer risk [15].
Recent evidence also suggests that the LAN theory may be applicable for other neoplasms such as prostate cancer [16], [17], [18], [19], [20], [21], endometrial cancer [22], [23], [24], and possibly colon cancer [25]. However, while the interaction between melatonin and skin is well established, the LAN theory has never been put forward to explain epidemiological trends for cutaneous melanoma. Here, we present the hypothesis that the increase in melanoma incidence over the past decades may be explained in part by the increasing use of artificial light, and we review and discuss supporting evidence from the existing literature.
Section snippets
The hypothesis
Since melatonin plays significant antioxidant and anti-carcinogenic roles in melanocytes (the skin cells from which melanomas arise) and considering that melatonin secretion is inhibited by the use of artificial light-at-night through a disruption of the circadian rhythm, we speculate that use of artificial light-at-night may increase the risk of melanoma by inducing loss of the cancer-preventive effects of melatonin. Alternatively, melatonin suppression may imply an imbalance in immune or
Experimental studies
Over the past 60 years, there has been increasing evidence suggesting that melatonin is synthesized not only by the pineal gland, but also at other sites such as the skin [8], [26], where it plays an important role in regulation of skin function and structure in response to different threats from the environment [8], [10]. Melatonin has also been shown to exhibit an important role in skin pigmentation and hair development: historically, melatonin was discovered because of its lightening effects
Discussion
Overall, the evidence reviewed above provides some support to the LAN hypothesis for increased melanoma risk. First, experimental studies show that melatonin is synthesised locally in the skin, where it plays important roles in skin function, structure, and the skin’s response to environmental stressors such as UVR. Melatonin receptors are expressed in melanocytes, where this hormone has been shown to exert anti-cancer properties, and melatonin has also been shown to have oncostatic effects on
Conflict of interest
None declared.
Funding source
Dr. Kvaskoff is supported by a Fondation de France postdoctoral fellowship.
Acknowledgements
The authors wish to thank Dr David Whiteman for his useful comments during the preparation of the manuscript.
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