September 4, 2012 — Researchers from Utah have uncovered a novel association between Parkinson's disease (PD) and prostate cancer, which extends to close and distant relatives. The relationship appears reciprocal, with relatives of individuals with prostate cancer at increased risk for PD.
In addition, the study confirms the known association between PD and melanoma, has extended it to close and distant relatives, and has determined that it, too, is reciprocal.
These results "strongly support a genetic link" between PD and these cancers, the authors note.
"The clinical implications suggest screening for melanoma and prostate cancer in appropriate PD patients and perhaps vice versa," study coauthor Lisa Cannon-Albright, PhD, from the University of Utah, in Salt Lake City, told Medscape Medical News.
Dr. Lisa A. Cannon-Albright
Their findings are published online September 3 in Archives of Neurology.
Unique Data Source
Data for the study came from the Utah Population Database, which includes the genealogy of Utah pioneers and their descendants, consisting of more than 2 million individuals with some records dating back more than 15 generations. This information was linked to data from the Utah Cancer Registry, which was established in 1966.
"This unique data resource has allowed us to ask quite complicated questions about disease associations that may have a genetic component by looking for congregation of the diseases in the cases and their relatives," Dr. Cannon-Albright explained.
Among 2998 patients with genealogy data whose death certificate listed PD as the cause of death, researchers observed 48 cases of melanoma, compared with only 24.6 expected cases. The estimated relative risk (RR) for melanoma in individuals with PD was 1.95 (95% confidence interval [CI], 1.44 - 2.59).
This finding supports a recent meta-analysis, published in Neurology and reported by Medscape Medical News, which found a 2-fold increased risk for melanoma in association with PD.
The Utah study also reported a statistically significant increased risk for melanoma among first-, second-, and third-degree relatives of individuals with PD.
Table. Estimated Risk for Melanoma With PD
| Relationship | Observed | Expected | RR (95% CI) |
| 1st degree | 217 | 176.8 | 1.23 (1.07 - 1.40) |
| 2nd degree | 429 | 383.1 | 1.12 (1.02 - 1.23) |
| 3rd degree | 1013 | 958.4 | 1.06 (0.99 - 1.12) |
CI, confidence interval; PD, Parkinson's disease; RR, relative risk.
Among 7841 individuals with the diagnosis of melanoma who had at least 3 generations of genealogy, a significantly increased risk for death with PD was noted among the melanoma cases themselves (RR, 1.65; 95% CI, 1.22 - 2.19) and among all relatives.
Prostate cancer was the only other cancer observed in excess (P < .01), the researchers say. They observed 212 cases in individuals with PD, against an expected 124 cases (RR, 1.71; 95% CI, 1.49 - 1.96). A significantly elevated risk for prostate cancer was also observed in relatives of individuals with PD.
Table. Estimated Risk for Prostate Cancer With PD
| Relationship | Observed | Expected | RR (95% CI) |
| 1st degree | 765 | 613.6 | 1.25 (1.16 - 1.34) |
| 2nd degree | 1194 | 1098.7 | 1.09 (1.03 - 1.15) |
| 3rd degree | 3504 | 3251.1 | 1.08 (1.04 - 1.11) |
CI, confidence interval; PD, Parkinson's disease; RR, relative risk.
Among 22,147 individuals with a diagnosis of prostate cancer and at least 3 generations of genealogy, a significantly increased risk for death with PD was noted among prostate cancer cases (RR, 1.39; 95% CI, 1.21 - 1.59), as well as their close and distant relatives.
Environment or Genetics?
In an editorial published with the study, Walter A. Rocca, MD, MPH, points out that the strength of these associations declined with a more distant genetic relationship but remained statistically significant, with greater strength for first-degree than for second-degree relatives, and for second-degree than for third-degree relatives.
This suggests that the associations are "more likely mediated by shared genetic factors than by shared environmental exposures," writes Dr. Rocca, from the Division of Epidemiology, Department of Health Sciences Research at Mayo Clinic, in Rochester, Minnesota.
He says that findings from this study, coupled with other findings, suggest that some families have a "genetic predisposition that can manifest as PD, as other types of parkinsonism, as essential tremor, as cognitive impairment or dementia, as amyotrophic lateral sclerosis, as anxiety disorders, as depressive disorders, or as nonneurological conditions such as melanoma and prostate cancer."
"This theory has both clinical and research implications," Dr. Rocca says. "Clinically, it is important to explain to patients with PD and their family members that the genetic predisposition to PD is restricted to patients with younger onset of symptoms. In addition, within the few families with a genetic predisposition to PD, family members may experience a wide range of clinical manifestations, not simply PD. Knowledge of this clustering of disease within families may also guide preventive interventions (such as particular screening tests) for family members of patients with PD, who may be at particularly high risk," he writes.
From a research perspective, Dr. Rocca says that it is important to understand the mechanisms that cause this clustering of conditions.
"If the mechanisms are primarily genetic, as suggested by the Utah study, then it may be possible to identify genetic variants that predispose to accelerated neurodegeneration and to increased oncogenesis in the same individual or among members of some particular families," Dr. Rocca concludes. "However, if PD is multifactorial at the individual level, dimorphic in men and women, and heterogeneous at the population level, the search for one or several genetic variants may not be productive."
The study was supported by the Utah Cancer Registry, which is funded by the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program; additional support was provided by the National Cancer Institute, the Utah State Department of Health, and the University of Utah. The authors and Dr. Rocca have disclosed no relevant financial relationships.
Arch Neurol. Published online September 3, 2012. Abstract Editorial
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