MELANOMA AND PARKINSON DISEASE INTERCONNECTED

Patients with Parkinson's disease (PD) have about a 4-fold increased risk of having preexisting melanoma and those with melanoma have a similar risk of developing PD, according to new retrospective, case-control analyses.

Despite the significantly heightened risks, the authors of the combined study stopped short of strongly recommending screening for all such patients.

Instead, they had less emphatic advice: "Physicians may consider counseling patients with melanoma about PD risk and implementing cutaneous and ocular melanoma surveillance in patients with PD."

"I think that the results of the study have to be replicated by others before coming out with stronger guidelines," said senior author, Jose Pulido, MD, MPH, from the Mayo Clinic in Rochester, Minnesota.

"In the meantime, I think that this should at least raise our awareness of the possible reciprocal association," he told Medscape Medical News.

The new study was published in the July issue of Mayo Clinic Proceedings.

Dating back to the early 1970s, there has been speculation about the relationship between PD and melanoma, the authors write. The initial theory was that the PD drug levodopa created a risk for the skin cancer. But subsequent randomized controlled trials and prospective studies did not confirm the hypothesis.

However, multiple other studies have since found an increased risk for melanoma in patients with PD, including a 7-fold increase in a recent prospective North American study (Mov Disord. 2014;29:263-265). 

PD and the Risk for Melanoma

To shed more light on the subject, the Mayo investigators performed a two-part, case-control study using their comprehensive medical records database of residents in local Olmsted County, Minnesota (the well-known Rochester Epidemiology Project).

In part 1 (dubbed the PD Cohort), they identified 974 PD cases diagnosed between 1976 and 2014 and examined the prevalence of melanoma in those patients compared with a control group of 2922 residents without PD.

Notably, all patients with PD were treated with continuous carbidopa-levodopa.

The team found 32 total cases of melanoma in the PD cohort and 63 cases in the control group.

In the PD group, only 6 melanomas were diagnosed after PD diagnosis. Thus, there were 26 "pre–index date" melanomas. (For each case, the index date was the time of the PD diagnosis, whereas for each control, the index date was the time at which the event occurred for the matched case.)

Examining pre–index date melanomas alone, the researchers performed logistic regression analysis, which revealed a 3.8-fold increased likelihood of patients with PD having a history of melanoma compared with controls (95% confidence interval [CI], 2.1 - 6.8; P < .001).

Melanoma is a curable disease if detected and treated early, the authors point out. "Thus, a compelling argument can be made for more aggressive melanoma-screening protocols in patients with PD," they write.

The authors also note that most melanomas diagnosed in the PD group were diagnosed before the diagnosis or treatment of PD. This is in contrast to the control group, in which most (42 of 63) melanomas were diagnosed after the index date.

"This makes a compelling case for a genetic association between melanoma and PD and argues against any role of levodopa in increasing melanoma risk," they assert.

Melanoma and the Risk for PD

In part 2 (dubbed the Melanoma Cohort), the investigators identified 1544 patients diagnosed with melanoma between 1976 and 2014 and compared them with a control group of 1544 residents without melanoma to assess the prevalence of PD.

There were 43 cases of PD in the melanoma cohort and 14 cases of PD in the control group. Again, the researchers tweaked the numbers according to index dates. In the end, using a Cox proportional hazards model, the researchers found that the melanoma cohort had a 4.2-fold increased risk for PD after the index date compared with controls (95% CI, 2.0 - 8.8; P < .001).

Common Abnormalities

In discussing both cohorts, the authors say that the results "provide supportive evidence for an association between PD and melanoma and discourage acceptance of previous suggestions that levodopa is the root cause of this link."

So what is at work here? The authors speculate that "it is more likely that there are common environmental, genetic, or immunologic abnormalities underlying both conditions in these patients."

As Dr Pulido commented, it is premature to state just exactly how clinicians should go about screening such patients. He and his coauthors conclude: "For now, because of the apparent increase in incidence of both diseases and their reciprocal relationships, it is important for physicians to be vigilant for 1 disease in the context of the other."

This study was made possible by the Rochester Epidemiology Project , which is supported by the National Institute on Aging. During the investigation, study authors received funding from a variety of potentially competing sources, including the VitreoRetinal Surgery Foundation, Research to Prevent Blindness, Paul Family, and Deshong Family.

Mayo Clin Proc.  2017;92:1070-1079. Abstract