Inserm, CESP Centre for Research in Epidemiology and Population Health, U1018, Nutrition, Hormones and Women's Health Team, Institut Gustave Roussy, F-94805, Villejuif, France.
Med Hypotheses. 2010 Sep;75(3):305-11. doi: 10.1016/j.mehy.2010.03.010. Epub 2010 Mar 29.
The incidence rate of cutaneous melanoma has been increasing faster than that of any other cancer in white-skinned populations over the past decades. The main risk factors for melanoma (i.e. exposure to sunlight, naevus count, phototype, and family history of melanoma) may not wholly explain the epidemiological trends observed for this cancer. The light-at-night theory postulates that increasing use of artificial light-at-night may contribute to the increasing breast cancer incidence through suppressed secretion of melatonin (a hormone produced in the dark and inhibited by light, which regulates circadian rhythms). Here, we postulate that this theory may also apply to melanoma and that it may explain a part of this cancer burden. Consistent with our hypothesis is evidence from experimental studies suggesting a lightening effect of melatonin on frog skin and mammal hair during seasonal changes, its antioxidant and anti-carcinogenic effects in skin melanocytes, as well as the expression of melatonin receptors in melanocytes. Also, epidemiological data suggest lower melatonin concentrations in melanoma patients compared with controls; a potential therapeutic effect of melatonin in patients with metastatic disease; a higher prevalence of melanoma in pilots and aircrews, with increased risks with higher time zones travelled; and increased melanoma risks in office workers exposed to fluorescent lighting. Moreover, melanoma incidence and seasonal patterns are consistent with a reduction of melatonin secretion with intensity of exposure to light, although it remains difficult to distinguish the effect of melatonin disruption from that of sun exposure on the basis of ecological studies. Finally, the reported associations between hormonal factors and melanoma are consistent with melatonin inhibition increasing the risk of melanoma by increasing circulating oestrogen levels. Despite the existing suggestive evidence, the light-at-night hypothesis has never been directly tested for melanoma. Very few studies examined the potential associations between melanoma risk and shift work or melatonin concentrations, and we found no studies reporting on the relationship between melanoma and number of sleeping hours, use of melatonin supplements, blindness, night-time city light levels, bedroom light levels, or clock genes polymorphisms. Therefore, since several observations support our hypothesis and very little research has been undertaken on this subject, we strongly encourage analytic epidemiological studies to test the light-at-night theory for melanoma causation.
在过去几十年中,白种人群体中皮肤黑色素瘤的发病率增长速度比其他任何癌症都要快。黑色素瘤的主要危险因素(即暴露于阳光、痣的数量、肤色和黑色素瘤家族史)可能并不能完全解释这种癌症的流行病学趋势。夜间光照理论假设,夜间人工光照的增加可能会通过抑制褪黑素(一种在黑暗中产生并被光照抑制的激素,它调节昼夜节律)的分泌而导致乳腺癌发病率的上升。在这里,我们假设该理论也适用于黑色素瘤,并且它可能解释了这种癌症负担的一部分。与我们的假设一致的是,实验研究的证据表明,褪黑素在季节性变化期间对青蛙皮肤和哺乳动物毛发有提亮作用,它对皮肤黑素细胞的抗氧化和抗癌作用,以及黑素细胞中褪黑素受体的表达。此外,流行病学数据表明,与对照组相比,黑色素瘤患者的褪黑素浓度较低;褪黑素对转移性疾病患者的潜在治疗作用;飞行员和机组人员中黑色素瘤的患病率较高,随着飞行时区的增加,风险也随之增加;以及暴露于荧光灯的办公室工作人员中黑色素瘤风险增加。此外,黑色素瘤的发病率和季节性模式与褪黑素分泌随光照强度的降低而降低一致,尽管基于生态学研究,仍然很难区分褪黑素破坏与暴露于阳光下对黑色素瘤风险的影响。最后,荷尔蒙因素与黑色素瘤之间的关联报告与褪黑素抑制通过增加循环雌激素水平增加黑色素瘤风险的观点一致。尽管存在提示性证据,但夜间光照假说从未直接针对黑色素瘤进行过测试。很少有研究检查黑色素瘤风险与轮班工作或褪黑素浓度之间的潜在关联,我们也没有发现报告黑色素瘤与睡眠时间、使用褪黑素补充剂、失明、夜间城市灯光水平、卧室灯光水平或时钟基因多态性之间关系的研究。因此,由于有几项观察结果支持我们的假设,并且针对这一主题的研究很少,因此我们强烈鼓励分析性流行病学研究来测试夜间光照理论对黑色素瘤病因的作用。