Meta-analysis of the relationship between Parkinson disease and melanoma

Abstract

Objective: To assess the epidemiologic evidence on melanoma in relation to Parkinson disease (PD) via systematic review and meta-analysis.Methods: Epidemiologic studies on melanoma and PD were searched using PubMed, Web of Science, Scoups, and Embase (1965 through June 2010). Eligible studies were those that reported risk estimates of melanoma among patients with PD or vice versa. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. Results:We identified 12 eligible publications on melanoma and PD: 8 had fewer than 10 cases with both PD and melanoma, and 7 provided gender-specific results. The pooled OR was 2.11 (95% CI 1.26-3.54) overall, 2.04 (1.55-2.69) for men, and 1.52 (0.85-2.75) for women. Analyses by temporal relationship found that melanoma occurrence was significantly higher after the diagnosis of PD (OR 3.61, 95% CI 1.49-8.77), but not before PD diagnosis (OR 1.07, 95% CI 0.62-1.84). Further analyses revealed that the lack of significance in the latter analysis was due to one study, which when excluded resulted in a significant association (OR 1.44, 95% CI 1.06-1.96). We also analyzed nonmelanoma skin cancers in relation to PD and found no significant relationship (OR 1.11, 95% CI 0.94-1.30). Conclusions:Collective epidemiologic evidence supports an association of PD with melanoma.Further research is needed to examine the nature and mechanisms of this relationship. Neurology Accumulating epidemiologic evidence suggests a low occurrence of most cancer types in patients with Parkinson disease (PD).1 Intriguingly, melanoma is among the few cancer types that are more likely to occur among patients with PD.2,3 A link between melanoma and PD was first suspected following a case report of recurrent malignant melanoma in a patient with PD treated with levodopa. 4 Since then, a number of case reports have suggested that levodopa therapy increased the risk of melanoma. Reviews of these case reports have concluded, however, that the relationship between levodopa therapy and melanoma was "coincidental rather than causal." 4 Although suspicions surrounding levodopa therapy and increased risk of melanoma were largely dismissed, findings from recent clinical and epidemiologic studies increasingly suggest that PD is associated with a higher risk of melanoma and vice versa. The evidence from these studies, however, is not conclusive. Both malignant melanoma and PD are rare, and most available studies had fewer than 10 cases with both diseases occurring in the same individual, thus reducing the statistical power to adequately analyze the relationship. In addition, variations in study design, disease identification, and other methodologic limitations further weaken the ability of individual studies to draw a solid conclusion. We therefore conducted a system-

Parkinson’s Disease, Melanoma, and Keratinocyte Carcinoma: A Population-Based Study

“…This is in contrast to a meta-analysis of 6 studies where PD at baseline was associated with a pooled OR of 3.61 (95% CI 1.49–8.77) for melanoma [6]. Interestingly, this meta-analysis and a more recent publication [21] found no positive association for melanoma preceding PD.…”

“…Most previous studies attempted to examine the temporal relationship between PD and melanoma in both directions. While such analyses may provide insights into how these 2 conditions are connected, their insidious onset and presumed long latency period make it difficult to extract a temporal sequence based on the available literature that suggests that these 2 conditions tended to co-occur without a clear temporal order [6]. …”

Genetic perspective on the role of the autophagy-lysosome pathway in Parkinson disease

“…7,9 Interestingly, GPNMB is an important gene in melanoma, 187 a skin malignancy that is associated with PD. 188 The GPNMB protein localizes mainly to melanosomes and to a lesser extent to lysosomes in melanoma cells; however, in other cells it localizes to lysosomes. 31 Furthermore, GPNMB is involved in phagocytosis, and is essential for recruitment of the autophagy protein LC3-II to the phagosome.…”

A Common Variant in the MC1R Gene (p.V92M) is associated with Alzheimer’s Disease Risk

“…Interestingly, two MC1R variants related to red hair color phenotype modulate the risk to develop PD [22,29]. These findings partially explain the previous epidemiological evidence describing a bidirectional link between PD and CM [21]. In contrast to PD, an increased incidence of CM among AD patients and overrepresentation of individuals with natural red hair within AD patients compared to control population has not been reported.…”

“…It has been established that several MC1R polymorphisms constitute a risk factor to develop skin cancer (melanoma and non-melanoma skin cancer) [18,19], in part, by promoting an increased oxidative stress in skin cells [20]. Notably, co-occurrence of Parkinson's disease (PD) and cutaneous melanoma (CM) has been reported in epidemiological studies [21] and previous evidence indicates that MC1R is involved in the bidirectional link between both diseases [22,23]. Thus, we hypothesized that certain MC1R variants may increase the oxidative damage and/or deregulate inflammatory processes in brain cells, which consequently, increase the susceptibility of developing other neurodegenerative disorders beyond PD.…”