Parkinson's Disease and Melanoma: Co-Occurrence and Mechanisms

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder that is characterized by loss of dopaminergic neurons in the substantia nigra pars compacta, depletion of dopamine in the striatum and the presence of Lewy bodies. Cancer is uncontrolled growth of cells in the body and migration of these cells from their site of origin to other parts of the body. PD and cancer are two opposite diseases, one arising from cell proliferation and the other from cell degeneration. This fundamental difference is consistent with inverse comorbidity between most cancers and neurodegenerative diseases. However, a positive association of PD and melanoma has been reported which has recently become of significant interest. A link between PD and cancer has been supported by many epidemiological studies, most of which show that PD patients have a lower risk of developing most cancers than the general population. However, the mechanisms underlying this epidemiological observation are not known. In this review we focus on epidemiological studies correlating PD and melanoma and the possible mechanisms underlying the co-occurrence of the two diseases. We explore possible explanations for the important observations that more PD patients develop melanoma that would otherwise be expected and vice-versa.

Keywords: Parkinson’s disease; genetic factors; levodopa; melanin; melanoma; neuromelanin; pesticides; tyrosinase; tyrosine hydroxylase.

Fig. 2

Schematic representation of possible mechanisms that can explain the co-occurrence of PD and melanoma.

Fig. 1

Genes responsible for melanoma and PD. A) CYP2D6 or GSTM1, VDR, MC1R gene alterations are found in both PD and Melanoma, providing a potential link between PD and Melanoma. B) Mutations in parkin, α-synuclein, LRRK2, DJ-1, and other PARK genes may underlie the co-occurrence of PD and Melanoma. TRPM7 and p53 are additional genes altered in PD and melanoma.