Diana Helis Henry Medical Research Foundation, New Orleans, LA, USA.
Int J Cancer. 2011 May 15;128(10):2251-60. doi: 10.1002/ijc.25912. Epub 2011 Mar 14.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by a loss of melanin-positive, dopaminergic neurons in the substantia nigra. Although there is convincing epidemiologic evidence of a negative association between PD and most cancers, a notable exception to this is that melanoma, a malignant tumor of melanin-producing cells in skin, occurs with higher-than-expected frequency among subjects with PD and that melanoma patients are more likely to have PD. A clear biological explanation for this epidemiological observation is lacking. Here, we present a comprehensive review of published literature exploring the association between PD and melanoma. On the basis of published findings, we conclude that (i) changes in pigmentation including melanin synthesis and/or melanin synthesis enzymes, such as tyrosinase and tyrosine hydroxylase, play important roles in altered vulnerability for both PD and melanoma; (ii) changes of PD-related genes such as Parkin, LRRK2 and α-synuclein may increase the risk of melanoma; (iii) changes in some low-penetrance genes such as cytochrome p450 debrisoquine hydroxylase locus, glutathione S-transferase M1 and vitamin D receptor could increase the risk for both PD and melanoma and (iv) impaired autophagy in both PD and melanoma could also explain the association between PD and melanoma. Future studies are required to address whether altered pigmentation, PD- or melanoma-related gene changes and/or changes in autophagy function induce oncogenesis or apoptosis. From a clinical point of view, early diagnosis of melanoma in PD patients is critical and can be enhanced by periodic dermatological surveillance, including skin biopsies.
帕金森病（PD）是一种神经退行性疾病，其特征是黑质中黑色素阳性、多巴胺能神经元丧失。尽管有令人信服的流行病学证据表明 PD 与大多数癌症之间存在负相关，但有一个显著的例外，即黑色素瘤，一种皮肤中黑色素产生细胞的恶性肿瘤，在 PD 患者中比预期更频繁地发生，并且黑色素瘤患者更有可能患有 PD。目前缺乏对这一流行病学观察结果的明确生物学解释。在这里，我们对已发表的文献进行了全面回顾，探讨了 PD 和黑色素瘤之间的关联。基于已发表的研究结果，我们得出结论：（i）包括黑色素合成和/或黑色素合成酶（如酪氨酸酶和酪氨酸羟化酶）在内的色素变化在 PD 和黑色素瘤的易感性改变中起着重要作用；（ii）PD 相关基因的改变，如 Parkin、LRRK2 和 α-突触核蛋白，可能会增加黑色素瘤的风险；（iii）一些低外显率基因的改变，如细胞色素 p450 脱异丙基酶羟化酶基因座、谷胱甘肽 S-转移酶 M1 和维生素 D 受体，可能会增加 PD 和黑色素瘤的风险；（iv）PD 和黑色素瘤中自噬的改变也可以解释 PD 和黑色素瘤之间的关联。需要进一步的研究来确定色素改变、PD 或黑色素瘤相关基因改变和/或自噬功能改变是否会导致肿瘤发生或细胞凋亡。从临床角度来看，早期诊断 PD 患者的黑色素瘤至关重要，可以通过定期的皮肤科监测，包括皮肤活检来增强。
