Focus on melanoma
Focus on melanoma
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DOI：
10.1016/s1535-6108(02)00161-7
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发表时间：
2002-10-01
期刊：
影响因子：
50.3
通讯作者：
Polsky, D
中科院分区：
文献类型：
--
作者：
Houghton, AN;Polsky, D
过去 50 年来，大多数发达国家黑色素瘤的发病率上升速度超过任何其他癌症类型。曾经是一种罕见的癌症，其发病率在 20 世纪 30 年代至 1970 年间急剧上升（每年 10%，每十年翻一番），在过去 30 年中减慢至目前的每年 05%（图 1）（Berwick 和 Halpern，1997 年；Oliveria 等人，2001 年）。死亡率也大幅上升，但速度较慢。在美国，每 82 名女性中就有 1 名以及每 58 名男性中就有 1 名会患上黑色素瘤。与大多数癌症不同，黑色素瘤的发病率并不强烈依赖于年龄，黑色素瘤是 20-35 岁年龄段癌症和癌症死亡的最常见原因之一。因此，对青壮年来说，社会经济和心理影响是巨大的。黑色素瘤提供了遗传和环境在癌症发病机制中如何相互作用的最佳例子之一。发病率受到种族和地理位置的强烈影响（Balch 等，2002）。黑色素瘤主要是一种色素沉着较浅的人群（即白种人）的疾病，而肤色较深的人群（例如非洲人、东亚人、西班牙人）的发病率要低 5 至 20 倍（见图 1）。在高加索人群中，发病率受到靠近赤道的影响，这表明与阳光照射有关。例如，美国南部的黑色素瘤发病率比美国北部高出两到三倍。移民研究进一步强调了环境的作用，因为当移民从高发地区迁移到低发地区时，仍然存在高风险。黑素细胞痣（痣）是黑素细胞的良性簇，作为潜在的前体病变而受到特别关注。然而，白种人平均每人有15-35个良性痣，单个良性痣变成黑色素瘤的风险极小。此外，只有010%–20%的原发性黑色素瘤与痣有关，这表明绝大多数原发性黑色素瘤并非由痣引起。另一方面，所谓的“非典型痣”是黑色素瘤风险增加的标志。例如，患有> 100个明显的非典型痣并且有黑色素瘤家族史的人患黑色素瘤的可能性非常高（终生风险接近100%）。然而，非典型痣的临床诊断标准都不是精确的或高度可重复的。非典型痣在白种人群体中普遍存在（高达 18%）。这些“非典型”病变迫切需要更可靠的分子定义标记。毫无争议的前兆病变是恶性雀斑样痣，这是一种良性色素病变，发生在严重暴露在阳光下的皮肤上，通常发生在老年人身上。据估计，5%–30% 的恶性雀斑样病变会进展为侵袭性恶性雀斑样黑色素瘤，将长期日晒与这种特殊类型的黑色素瘤联系起来。
Over the past 50 years, the incidence of melanoma in most developed countries has risen faster than any other cancer type. Once a rare cancer, incidence rose dramatically between the 1930s and 1970 (010%/year, doubling every ten years), slowing to its present rate of 05%/year over the last 30 years (Figure 1)(Berwick and Halpern, 1997; Oliveria et al., 2001). Mortality rates have also risen substantially, although at a slower rate. In the US, 1 in 82 women and 1 in 58 men will develop melanoma. Unlike the majority of cancers, melanoma incidence is not strongly dependent on age, and melanoma is one of the most common causes of cancer and cancer deaths between the ages of 20–35. Thus, by afflicting young and middle-aged adults, the socioeconomic and psychological impact is great. Melanoma provides one of the best examples of how genetics and environment interact in the pathogenesis of cancer. Incidence is strongly affected by race and geographic location (Balch et al., 2002). Melanoma is predominantly a disease of populations with lighter pigmentation (ie, Caucasians) and incidence is 5-to 20-fold lower in populations with darker skin color (eg, Africans, East Asians, Hispanics)(see Figure 1). Within Caucasian populations, incidence is influenced by proximity to the equator, suggesting a link to solar exposure. For instance, melanoma incidence in the southern US is two to three times higher than the northern US Studies of migrants further emphasize the role of environment, based on retained high-risk when migrants moved from high incidence to lower incidence areas. Melanocytic nevi (moles), benign clusters of melanocytes, have drawn special attention as potential precursor lesions. However, Caucasians have an average of 15–35 benign common nevi per person, and the risk of an individual benign common nevus becoming melanoma is extremely small. In addition, only 010%–20% of primary melanomas are associated with nevi, suggesting that the large majority of primary melanomas do not arise from nevi. On the other hand, so-called “atypical nevi” are a marker for increased risk for melanoma. For instance, persons with> 100 flagrant atypical nevi and a family history of melanoma have a very high probability (lifetime risks approaching 100%) of developing melanoma. However, none of the clinical diagnostic criteria for atypical nevi are precise or highly reproducible. Atypical nevi are prevalent in Caucasian populations (as high as 18% of individuals). There is a desperate need for more reliable, molecularly defined markers for these “atypical” lesions. An undisputed precursor lesion is lentigo maligna, a benign pigmented lesion occurring on heavily sun-exposed skin usually in elderly individuals. It is estimated that 5%–30% of lentigo maligna lesions progress to invasive lentigo maligna melanoma, linking chronic sun exposure to this special type of melanoma.