Parkinson's disease (PD) is a neurodegenerative disorder characterized by a loss of melanin-positive, dopaminergic neurons in the substantia nigra (SN). 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. Based on published findings, we conclude that (1) changes in pigmentation including melanin synthesis and/or melanin synthesis enzymes such as tyrosinase (TYR) and tyrosine hydroxylase (TH), play important roles in altered vulnerability for both PD and melanoma; (2) Changes of PD-related genes such as Parkin, LRRK2, and α-synuclein may increase the risk of melanoma; (3) changes in some low-penetrance genes such as cytochrome p450 debrisoquine hydroxylase locus (CYP2D6), glutathione S-transferase M1 (GSTM1) and vitamin D receptor (VDR) could increase the risk for both PD and melanoma; (4) 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.

PMID: 21207412 [PubMed - as supplied by publisher] Source: National Library of Medicine.