Are People With Parkinson’s at Higher Risk for Melanoma?

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

Comments

  1. It was exciting to read the paper by Liu and colleagues, one for which I had been waiting. When researching the literature for the meta-analysis I wrote on PD and non-melanoma cancers (showing reduced cancer risk ratios with relative risk of 0.73 and a 95 percent confidence interval of 0.63-0.83; referenced by Liu et al.), I came across many studies that individually showed an increased risk of melanoma in PD patients. By summing the studies available on the subject, the work by Liu et al. affirms the idea that an association between melanoma and PD exists. It is unclear why there is a reduced risk of some cancers (e.g., lung cancer, leukemias and lymphomas, colorectal cancer) and an increased risk of melanoma, and how these cancers are linked to PD. Certainly, future studies attempting to delineate the biological mechanism underlying these questions are warranted.

    View all comments by Archna Bajaj

  2. I would note that since the overall prevalence of melanoma in Parkinson's disease (PD) is pretty low, it is difficult to see a large role for melanoma-related mechanisms in PD, or vice versa.

    Also, the extra medical attention that a subject gets after being diagnosed with a disease like PD may lead to increased detection of melanoma.

    Finally, the PD cases in these clinical epidemiological studies were not verified neuropathologically, so there is an approximate 15-35 percent error rate built into the classification of PD versus non-PD (see Hughes et al., 2001 for clinical diagnostic accuracy rate).

    In our Banner Sun Health Research Institute Brain and Body Donation Program, we have 121 neuropathologically verified cases of PD, of which three had a history of melanoma. Of the 750 subjects without neuropathologically verified PD, 23 subjects had melanoma. This comes out to a rate of 2.36 cases of melanoma to 100 PD subjects and 3.07 cases of melanoma per 100 cases of non-PD.

    References:

    Hughes AJ, Ben-Shlomo Y, Daniel SE, Lees AJ. What features improve the accuracy of clinical diagnosis in Parkinson's disease: a clinicopathologic study. 1992. Neurology. 2001 Nov;57(10 Suppl 3):S34-8. PubMed.

    View all comments by Thomas Beach

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References

News Citations

  1. Putting the Squeeze on Vascularization—A Link Between Cancer and Aβ?

Paper Citations

  1. Inzelberg R, Israeli-Korn SD. The particular relationship between Parkinson's disease and malignancy: a focus on skin cancers. J Neural Transm. 2009 Nov;116(11):1503-7. PubMed.
  2. Ferreira JJ, Neutel D, Mestre T, Coelho M, Rosa MM, Rascol O, Sampaio C. Skin cancer and Parkinson's disease. Mov Disord. 2010 Jan 30;25(2):139-48. PubMed.
  3. Fiala KH, Whetteckey J, Manyam BV. Malignant melanoma and levodopa in Parkinson's disease: causality or coincidence?. Parkinsonism Relat Disord. 2003 Aug;9(6):321-7. PubMed.
  4. Herrero Hernández E. Pigmentation genes link Parkinson's disease to melanoma, opening a window on both etiologies. Med Hypotheses. 2009 Mar;72(3):280-4. PubMed.
  5. Paisán-Ruiz C, Houlden H. Common pathogenic pathways in melanoma and Parkinson disease. Neurology. 2010 Nov 2;75(18):1653-5. PubMed.
  6. Matsuo Y, Kamitani T. Parkinson's disease-related protein, alpha-synuclein, in malignant melanoma. PLoS One. 2010;5(5):e10481. PubMed.
  8. Bajaj A, Driver JA, Schernhammer ES. Parkinson's disease and cancer risk: a systematic review and meta-analysis. Cancer Causes Control. 2010 May;21(5):697-707. PubMed.

External Citations

  1. melanocortin-1 receptor
  2. Skin Cancer Foundation

Further Reading

Primary Papers

  1. 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. PubMed.

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