Armstrong Bruce K, Cust Anne E
Cancer Epidemiology and Prevention Research Group, School of Public Health, The University of Sydney, NSW, Australia; School of Global and Population Health, The University of Western Australia, Perth, WA, Australia.
Cancer Epidemiology and Prevention Research Group, School of Public Health, The University of Sydney, NSW, Australia; The Melanoma Institute Australia, North Sydney, NSW, Australia.
Cancer Epidemiol. 2017 Jun;48:147-156. doi: 10.1016/j.canep.2017.04.004. Epub 2017 May 3.
Sunlight has been known as an important cause of skin cancer since around the turn of the 20th Century. A 1977 landmark paper of US scientists Fears, Scotto, and Schneiderman advanced a novel hypothesis whereby cutaneous melanoma was primarily caused by intermittent sun exposure (i.e. periodic, brief episodes of exposure to high-intensity ultraviolet radiation) while the keratinocyte cancers, squamous cell carcinoma and basal cell carcinoma, were primarily caused by progressive accumulation of sun exposure. With respect to cutaneous melanoma, this became known as the intermittent exposure hypothesis. The hypothesis stemmed from analysis of measured ambient ultraviolet radiation and age-specific incidence rates of melanoma and keratinocyte cancers collected as an extension to the US Third National Cancer Survey in several US States. In this perspective paper, we put this novel hypothesis into the context of knowledge at the time, and describe subsequent epidemiological and molecular research into melanoma that elaborated the intermittent exposure hypothesis and ultimately replaced it with a dual pathway hypothesis. Our present understanding is of two distinct biological pathways by which cutaneous melanoma might develop; a nevus prone pathway initiated by early sun exposure and promoted by intermittent sun exposure or possibly host factors; and a chronic sun exposure pathway in sun sensitive people who progressively accumulate sun exposure to the sites of future melanomas.
自20世纪之交以来，阳光一直被认为是皮肤癌的一个重要病因。1977年，美国科学家菲尔斯、斯科托和施奈德曼发表了一篇具有里程碑意义的论文，提出了一个新的假说，即皮肤黑素瘤主要是由间歇性阳光照射（即周期性、短暂暴露于高强度紫外线辐射）引起的，而角质形成细胞癌，即鳞状细胞癌和基底细胞癌，则主要是由阳光照射的逐渐积累引起的。关于皮肤黑素瘤，这一假说被称为间歇性暴露假说。该假说源于对测量的环境紫外线辐射以及作为美国第三次全国癌症调查扩展部分收集的几个美国州黑素瘤和角质形成细胞癌的年龄特异性发病率的分析。在这篇观点论文中，我们将这一新假说置于当时的知识背景下，并描述了随后对黑素瘤的流行病学和分子研究，这些研究阐述了间歇性暴露假说，并最终用双途径假说取代了它。我们目前的认识是，皮肤黑素瘤可能通过两种不同的生物学途径发展；一种是痣倾向途径，由早期阳光照射引发，并由间歇性阳光照射或可能的宿主因素促进；另一种是慢性阳光照射途径，发生在对阳光敏感的人群中，他们逐渐将阳光照射积累到未来黑素瘤的发病部位。
