10 June 2011. Neurodegenerative conditions such as Alzheimer’s disease and Parkinson’s disease are typically linked to a lower risk of getting cancer, but a new study shows there are exceptions to this rule. Researchers led by Honglei Chen at the National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, report in the June Neurology that people with PD have about double the chance of having melanoma, the most dangerous form of skin cancer. It is unclear why this might be, but Chen and colleagues suggest the two disorders may share common pathways, and that further research into the phenomenon might yield clues to the causes of both diseases.
Previous studies have found a higher occurrence of melanoma among people with PD, and vice versa (see, e.g., Inzelberg and Israeli-Korn, 2009; Ferreira et al., 2010). They were small, however, usually including fewer than 10 participants who had both conditions, and the results were not conclusive. To overcome this limitation, Chen and colleagues performed a meta-analysis of 12 publications. The combined data showed that melanoma cases were about twice as common among PD patients as in the control population. The researchers saw no clear temporal relationship, finding that melanomas occurred before PD diagnosis as well as after. The increased occurrence was specific to melanoma, with no consistent association between PD and other types of skin cancer. The PD-melanoma link occurred in both men and women, although the data were stronger for men.
Earlier case reports had suggested that people with PD might be more vulnerable to melanoma because they receive the drug levodopa, which can stimulate the production of melanin. However, later studies have not supported this idea (see Fiala et al., 2003), and the finding that many melanomas form before Parkinson’s is diagnosed, as well as in patients who do not take levodopa, suggests the drug cannot explain the association, the authors note.
Instead, Chen and colleagues suggest that Parkinson’s and melanoma may share some biological pathways, a hypothesis also proposed by others (see, e.g., Herrero Hernández, 2009; Paisán-Ruiz and Houlden, 2010). The authors point out that neurons and melanocytes, the cells responsible for melanoma, have a common embryonic origin. Both dopamine and melanin pigments are synthesized from the amino acid tyrosine, although by separate enzymatic routes. Dopaminergic neurons in the substantia nigra produce a form of melanin, neuromelanin, which gives the cells their dark color. The main protein in Parkinson’s deposits, α-synuclein, also appears in melanocytic lesions (see Matsuo and Kamitani, 2010). Perhaps most tellingly, a genetic variation in the melanocortin-1 receptor is linked both to red hair and to a two- to threefold higher risk of PD (see Gao et al., 2009).
Chen and colleagues plan to use clinical and epidemiological studies to explore whether genetic and environmental factors can explain the relationship between PD and melanoma. “We need to understand why and how these two conditions are correlated; this may eventually help us understand the etiologies of both,” he wrote. He would also like to see larger epidemiological studies that include more women and better-defined dates of PD onset to help tease out temporal and gender relationships between the disorders. Animal research will also be needed to dissect the biological mechanisms, Chen added.
The populations included in this meta-analysis were predominantly light-skinned, all from Europe or North America. Melanoma risk is about 20 times lower in dark-skinned populations, as their high levels of melanin protect them from the ultraviolet radiation damage that promotes melanoma. “We need more research among minorities, particularly in African-Americans,” Chen wrote to ARF, but he noted that such studies will be difficult because of the lower incidence of PD among this population.
In terms of public health, Chen noted that clinicians should be alerted to watch for melanoma in PD patients, “but as both PD and melanoma are relatively rare, no one should be alarmed.” When caught early, the survival rate for melanoma is 99 percent, according to figures from the Skin Cancer Foundation.
It is not clear why people with PD have a low risk for most other forms of cancer (see review from Bajaj et al., 2010). AD patients are also less likely to get cancer. One proposed explanation is that the AD brain creates an anti-angiogenic environment (see ARF related news story). Cathy Roe at the University of Washington in St. Louis, Missouri, who studies the AD-cancer connection, notes that it is hard to get good datasets for examining the associations between specific types of cancer and AD, but adds that such studies will be important for identifying common pathways that might help researchers tackle the disorders.—Madolyn Bowman Rogers.
Liu R, Gao X, Lu Y, Chen H. Meta-analysis of the relationship between Parkinson disease and melanoma. Neurology. 2011 Jun 7;76(23):2002-9. Abstract