Variations in the ‘Ginger Hair’ Gene May Link Melanoma and Parkinson’s Disease

The MC1R gene is associated with ginger hair and fair skin and has been considered a risk factor for melanoma (skin cancer). Now, a new study hypothesizes that this gene also may increase the risk of Parkinson’s disease by affecting dopamine production.

The study “The Melanoma-Linked “Redhead” MC1R Influences Dopaminergic Neuron Survival” was published in the journal Annals of Neurology.

Parkinson’s disease patients are more likely to develop melanoma, and patients with melanoma also are at higher risk of developing Parkinson’s disease.

Melanoma has been associated with variations in the MC1R gene, which is involved in skin pigmentation. (When the gene is active, there is greater production of a darker skin pigment, but when it’s inactive, individuals have fairer skin and ginger hair.) This led researchers to wonder if such variations also could be related to Parkinson’s disease.

Using mice carrying a mutation that inactivates the MC1R gene, researchers observed that dopamine production was decreased in a brain area called the substantia nigra, which is affected in patients with Parkinson’s disease. Also, neurons in this area were more susceptible to toxins known to damage their function.

However, treatment of these animals with a selective activator of the MC1R protein protected neurons against induced toxicity.

“This study is the first to show direct influences of the melanoma-linked MC1R gene on dopaminergic neurons in the brain and may provide evidence for targeting MC1R as a novel therapeutic strategy for PD,” Xiqun Chen, MD, PhD and study’s senior author, said in a press release. “It also forms a foundation for further interdisciplinary investigations into the dual role of this gene in tumorigenesis within melanocytes — the pigment cells in which melanoma develops — and the degeneration of dopaminergic neurons, improving our understanding of why and how melanoma and Parkinson’s disease are linked.”

“Since MC1R regulates pigmentation and red hair is a shared risk factor for both melanoma and Parkinson’s disease, it is possible that, in both conditions, MC1R’s role involves pigmentation and related oxidative stress,” said Chen, whose team did its investigation at Massachusetts General Hospital.

“Our findings suggest further investigation into the potential of MC1R-activating agents as novel neuroprotective therapies for [Parkinson’s disease], and together with epidemiological evidence, may offer information that could guide those carrying MC1R variants to seek advice from dermatologists or neurologists about their personal risk for melanoma and Parkinson’s disease.”