Increased Odds of Melanoma: Parkinson's Disease, Essential Tremor, Dystonia versus Controls

Abstract

Objective: Patients with Parkinson's disease (PD) have an increased risk of melanoma, although the mechanisms are unclear. We are unaware of studies that have assessed the association between other movement disorders, such as essential tremor (ET) and dystonia, and melanoma. In this study, we assessed the association between ET, PD, dystonia and cancer (esp. melanoma). Methods: One hundred and eight PD cases, 139 ET cases, and 54 dystonia cases, and 124 controls were enrolled in a research study of the epidemiology of movement disorders (total n = 425). The groups were frequency matched on age and gender. Cancer diagnoses were made based on self-reports. Melanoma diagnoses were further validated. Results: The prevalence of melanoma was higher in PD cases than controls (13.9 vs. 1.6%, p < 0.001), and was marginally higher in ET cases (5.8%, p = 0.08) and dystonia cases (7.4%, p = 0.06) than controls. In adjusted logistic regression models, the odds of melanoma was 7.09-9.84 times higher in PD cases than controls (p values 0.01-0.003), 3.73-4.10 times higher in ET cases than controls (p values 0.08-0.10), and 4.88-5.27 times higher in dystonia cases than controls (p values 0.06-0.07). Conclusion: The links between neurological disorders and melanoma, long-known, may not be specific to PD and may extend to other movement disorders.

Essential Tremor and Parkinson’s Disease: Exploring the Relationship

“…Mood disturbances and apathy, similar to those in PD, have also been reported at an increased frequency in ET patients 46–50. This, however, may not be specific as there are many other disorders associated with depression and other mood changes.…”

“…rest tremor, cogwheeling, postural instability26,28–30,58Slowed reaction times31,32Preserved olfaction in tremor dominant PD patients with family history of tremor41Cognitive dysfunction (primarily frontal/executive problems)42–46Increased frequency of anxiety, depression, and apathy45,47,112,113Increased frequency of RBD and daytime somnolence22,45,47,48Emergence of PD after long-standing ET27PD asymmetry correlating with historical tremor asymmetry and severity27,36Increased incidence of rest and action tremor in ET–PD group versus PD38Increased cerebellar signs and more diffuse tremor in ET–PD patients than isolated PD patients39Increased risk of melanoma in PD and ET49,50Decreased risk of PD and ET among smokers51–53EpidemiologicIncreased prevalence of PD in ET patients relative to general population54–57Increased prevalence of ET in family members of PD patients60–65Increased prevalence of tremor dominant PD in ET families37Increased family history of tremor in relatives of ET–PD patients than isolated PD patients38,40ImagingHyperechogenicity in substantia nigra of ET patients associated with progression to PD68Reduced striatal dopamine uptake on DaTscan69–71PathologicOverlapping cerebellar pathology of changes in climbing fiber density and torpedoes74,75,77,78Lewy bodies in brains of ET patients75,77Genetic (strong family history and putative genes) LINGO1 93–96 LINGO2 96,97 HS1BP3 98,99 DNAJC13 100 HTRA2 102 NAACP-Rep1 103 CACNA1G (Cav3.1) Abbreviations...…”

“…While not symptoms per se , other similarities between ET and PD populations include a greater risk in developing melanoma,49,50 and a decreased risk of in both conditions among smokers 51–53…”

Systematic analysis of genetic variants in patients with essential tremor

“…The putative association between the potential risk variants of PD and the development of ET was investigated in ET patients and ethnically matched normal controls for a common genetic link, due to the considerable epidemiological, clinical, imaging, genetic, and neuropathological overlaps between ET and PD (Thenganatt & Jankovic, ). PD patients are reported to have an increased odds of melanoma, and the MC1R gene variants in humans are related to an increased risk of melanoma and PD (Chen, Chen, et al, ; Shalaby & Louis, ). This study suggests that the MC1R rs34090186 variant may be associated with ET in a Han Chinese population.…”

“…Epidemiologic, clinical, imaging, genetic, and pathologic features support a conclusion of a relationship between ET and PD, showing possible common mechanisms shared in two tremor disorders (Jimenez‐Jimenez et al, ; Louis, Clark, & Ottman, ; Thenganatt & Jankovic, ). In this scenario, association studies performed in PD patients are extended to studies in ET cases (He et al, ; Shalaby & Louis, ; Unal Gulsuner et al, ; Yuan, Song, Deng, Zheng, Guo, et al, ; Yuan, Song, Deng, Zheng, Yang, et al, ).…”