1st Department of Neurology, Eginition Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece.
Nuclear Medicine Unit, Attikon Hospital, 12462 Athens, Greece.
Medicina (Kaunas). 2023 Jul 25;59(8):1360. doi: 10.3390/medicina59081360.
Previous epidemiological evidence has established the co-occurrence of malignant melanoma (MM) and Parkinson's disease (PD). Shared molecular mechanisms have been proposed to be implicated in this relationship. The aim of the present study was to assess the prevalence of MM in patients with sporadic and genetic types of PD, as well as in asymptomatic carriers of PD-related genes. Data regarding past medical history and concomitant disease of 1416 patients with PD (including 20 participants with prodromal disease who phenoconverted to PD), 275 healthy controls (HCs) and 670 asymptomatic carriers of PD-related genes were obtained from the database of the Parkinson's Progression Markers Initiative (PPMI). Focus was placed on information about a medical record of MM. We also retrieved data regarding the genetic status of selected PPMI participants with a positive MM history. In total, 46 patients with PD reported a positive MM history. Concerning the genetic forms of PD, nine of these PD patients (2.47%) carried a Leucine Rich Repeat Kinase 2 (LRRK2) gene mutation (mainly the G2019S), while eight (4.49%) harbored a Glucocerebrosidase (GBA) gene mutation (mainly the N370S). No alpha-synuclein (SNCA) gene mutation was identified in patients with an MM history. The remaining 29 PD patients (3.5%) were genetically undetermined. In total, 18 asymptomatic carriers of PD-related genes had a positive medical history for MM: among them, 10 carried an LRRK2 gene mutation (2.69%) and 10 a GBA gene mutation (3.51%) (2 were dual carriers). MM history was identified for seven HCs (2.5%). We replicated the previously reported association between genetically undetermined PD (GU-PD) and MM. A correlation of LRRK2 mutations with the development of MM could not be verified in either symptomatic PD patients or asymptomatic carriers, implicating distinct pathogenetic mechanisms as compared to GU-PD. Importantly, despite the limited literature evidence on Gaucher disease, this study highlights for the first time the relatively high prevalence of MM among asymptomatic and symptomatic PD GBA mutation carriers, with potential clinical implications.
先前的流行病学证据表明，恶性黑色素瘤（MM）和帕金森病（PD）同时发生。已提出共同的分子机制与此相关。本研究旨在评估散发性和遗传性 PD 患者、PD 相关基因无症状携带者中 MM 的患病率。从帕金森病进展标志物倡议（PPMI）数据库中获取了 1416 名 PD 患者（包括 20 名疾病前患者，这些患者已转化为 PD）、275 名健康对照（HC）和 670 名 PD 相关基因无症状携带者的既往病史和合并症数据。重点是有关 MM 病历的信息。我们还检索了具有 MM 阳性病史的选定 PPMI 参与者的遗传状况数据。共有 46 名 PD 患者报告了 MM 阳性病史。关于 PD 的遗传形式，这些 PD 患者中有 9 人（2.47%）携带富亮氨酸重复激酶 2（LRRK2）基因突变（主要是 G2019S），而 8 人（4.49%）携带葡萄糖脑苷脂酶（GBA）基因突变（主要是 N370S）。在有 MM 病史的患者中未发现 alpha-突触核蛋白（SNCA）基因突变。其余 29 名 PD 患者（3.5%）遗传未确定。共有 18 名 PD 相关基因的无症状携带者有 MM 的阳性病史：其中 10 人携带 LRRK2 基因突变（2.69%），10 人携带 GBA 基因突变（3.51%）（2 人为双重携带者）。在 7 名 HC（2.5%）中发现了 MM 病史。我们复制了先前报道的遗传未确定 PD（GU-PD）与 MM 之间的关联。在有症状的 PD 患者或无症状携带者中，LRRK2 突变与 MM 的发展之间没有相关性，这表明与 GU-PD 相比存在不同的发病机制。重要的是，尽管关于戈谢病的文献证据有限，但本研究首次强调了无症状和有症状的 PD GBA 突变携带者中 MM 的相对高发率，这具有潜在的临床意义。
