Progress and Prospects in Parkinson's Research/Causes/Infection/Melanoma

"There appear to be a growing consensus of epidemiological evidence for a link between the risk of melanoma and the risk of PD. There is as yet no working hypothesis to explain this although the common themes of UV processing of Vitamin D3 may be significant."

Background
Melanoma is the most dangerous form of skin cancer and is frequently fatal. The risk of getting it increases with age and once initiated it can spread very rapidly. It can have genetic associations but the principle causative factor is exposure of the skin to sunlight or tanning machines and in particular over-exposure to ultra-violet radiation.

Research
2005

Freedman, et al followed 1.9 million cancer survivors who were diagnosed between 1973 and 2000 and who survived at least 1 year, through the year 2000.

"In this exploratory study, we observed a modest, significant association between melanoma and both ALS and Parkinson's disease mortality. It would be useful to explore these findings in other large national databases."

2006

Olsen et al carried out a Danish study which investigated the prevalence of malignant melanoma, skin carcinoma, and other cancers before a first hospitalization or outpatient visit for Parkinson disease.

"We observed an increased prevalence of malignant melanoma and skin carcinoma prior to the first hospital contact for Parkinson disease, with overall odds ratios of 1.44 (95% confidence intervals = 1.03-2.01) and 1.26 (1.11-1.43), respectively."

2007

Baade et al conducted a study of all people diagnosed as having melanoma in Australia since 1982 (n = 127,037). They then compared their mortality risk of amyotrophic lateral sclerosis (ALS) and PD to that of the general population. There were a total of 53 ALS deaths and 129 deaths due to PD. Although the absolute risk is small, the melanoma cohort had a risk of death due to ALS 70% higher (standardised mortality ratio = 169.4, 95% CI = 127-221) than the general population, and nearly a 3-fold increased risk of dying from PD (standardised mortality ratio = 266.3, 95% CI = 222-317).

2009

Gao et al examined the associations between a family history of melanoma and PD among 157,036 men and women. Their conclusions state:-

“In this prospective analysis, we found an approximately twofold increase in risk of PD among individuals who reported a family history of melanoma in a first-degree relative, as compared with those without such a family history”

Gao et al examined whether hair colour, one of the most important phenotypes of pigmentation and a risk factor for melanoma, was associated with PD risk. They found that:- "PD risk increased with decreasing darkness of hair color. Pooled RRs for PD were 1 (reference), 1.40, 1.61, and 1.93 (95% confidence interval, 1.1-3.4) for black, brown, blond, and red hair, respectively, after adjusting for age, smoking, ethnicity, and other covariates. The associations between hair color and PD were particularly strong for relatively younger onset of PD (<70 yr) (adjusted RR for red vs black hair = 3.83; 95% confidence interval, 1.7-8.7). In the case-control study, participants with Cys/Cys genotype, which was associated with red hair, had a greater PD risk, relative to the Arg/Arg genotype (adjusted RR, 3.15; 95% confidence interval, 1.1-9.4)."

2011

These conclusions were supported by research by Pan et al whose findings stated that:-

''On the basis of published findings, we conclude that (i) changes in pigmentation including melanin synthesis and/or melanin synthesis enzymes, such as tyrosinase and tyrosine hydroxylase, play important roles in altered vulnerability for both PD and melanoma; (ii) changes of PD-related genes such as Parkin, LRRK2 and α-synuclein may increase the risk of melanoma; (iii) changes in some low-penetrance genes such as cytochrome p450 debrisoquine hydroxylase locus, glutathione S-transferase M1 and vitamin D receptor could increase the risk for both PD and melanoma and (iv) impaired autophagy in both PD and melanoma could also explain the association between PD and melanoma.... ... 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.''

Rui et al assessed the epidemiological evidence for a relationship and melanoma. The outcome:-

''Collective epidemiologic evidence supports an association of PD with melanoma. Further research is needed to examine the nature and mechanisms of this relationship.''

2012

Pan et al evaluated the relationship of the alpha synuclein protein and melanin in dopaminergic cells. Their findings:-

" We found that α-Syn expression reduced UVB light-induced increase of melanin synthesis and that melanin content was lower when melanoma cells were expressed with α-Syn, indicating that α-Syn may have inhibitory effects on melanin synthesis in melanoma cells……We concluded that α-Syn could be one of the points responsible for the positive association between PD and melanoma via its differential roles in melanin synthesis in melanoma cells and in dopaminergic neuronal cells."

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Vitamin D