Men with Parkinson's disease had a significantly increased risk of prostate cancer, which had a reciprocal association with the neurologic disorder, according to analyses of two large databases.
The prostate cancer excess ranged from 71% to 8%, declining as a relative's degree of separation from a proband increased. Analysis of prostate cancer cases showed an increased risk of Parkinson's disease, which ranged from 39% to 8%, depending on a relative's genetic distance from the primary case.
The analyses of Utah pioneers and descendants also confirmed a previously reported strong association between Parkinson's disease and melanoma, as reported in the September issue of Archives of Neurology.
"These results strongly support a genetic link," Lisa Cannon-Albright, PhD, of the University of Utah in Salt Lake City, and co-authors wrote. "This conclusion is further strengthened by observation of the reciprocal relationship, an increased risk for Parkinson's disease in relatives of individuals with melanoma or prostate cancer."
Most studies of the relationship between Parkinson's disease and cancer have shown reduced rates of cancer. Melanoma has represented the notable exception, as investigators in Europe and the U.S. have previously reported an increased prevalence of melanoma in patients with Parkinson's disease, according to the authors' background information.
Initially, the association between Parkinson's and melanoma appeared limited to patients treated with levodopa. Subsequent large population-based studies showed a broader relationship that was independent of levodopa. The association was strengthened by reports of an increased prevalence of Parkinson's disease in patients with melanoma, as well as in first-degree relatives.
More recently, investigators reported an association with prostate cancer among patients with Parkinson's disease treated with entacapone (Comtan), carbidopa (Lodosyn), or levodopa. The observation prompted the FDA to issue an alert about the association.
Cannon-Albright and colleagues continued the investigation of Parkinson's' relationship to cancer with an analysis of a computerized genealogy for Utah pioneers and descendants linked to statewide cancer and death records.
The Utah Population Database comprises birth, death, and family relationship data for 2 million individuals, dating as far back as 15 generations in some cases. The database includes genealogic information for Utah's original settlers. The genealogic data were linked to state death certificates dating to 1904 and to a state cancer registry, which was established in 1966.
From the genealogy data, the investigators identified 2,998 individuals whose death certificates listed Parkinson's disease as the cause of death. In the Parkinson's subgroup, 48 cases of melanoma were found, whereas only 24.6 cases would normally be expected. The difference represented a relative risk for melanoma of 1.95 (95% CI 1.44 to 2.59).
A melanoma excess persisted among relatives of all degree relationship to the person who died with Parkinson's disease. The relationship remained significant in first- and second-degree relatives.
Cannon-Albright and colleagues also estimated the reciprocal relative risk for Parkinson's disease among individuals with melanoma diagnoses and among their first-, second-, and third-degree relatives. The analysis identified 7,841 melanoma cases involving individuals with at least three generations of genealogy data.
The relative risk of death with Parkinson's disease was 1.65 (95% CI 1.22 to 2.19), and the risk of Parkinson's disease death remained significant among all relatives of individuals who had melanoma diagnoses.
Investigators estimated the relative risk of 35 additional types of cancer among the 2,998 people who died of Parkinson's disease. Prostate cancer emerged as the only cancer with a significant relationship to Parkinson's. The analysis identified 212 cases of prostate cancer, whereas 124.1 would have been expected (RR 1.71, 95% CI 1.49 to 1.96, P<0.01).
The authors also estimated the reciprocal relative risk of Parkinson's disease in 22,147 individuals with prostate cancer and at least three generations of genealogy.
The result was a statistically significant 39% increased risk of Parkinson's disease (RR 1.39, 95% CI 1.21 to 1.59). The association remained significant in first-, second-, and third-degree relatives.
The analysis also revealed four cancers that occurred less often than expected among individuals with Parkinson's disease: colorectal, lung/bronchus, pancreas, and stomach. The association was significant only for lung/bronchus cancer (P<0.001).
The findings add to existing evidence of common underlying causes for Parkinson's disease and certain types of cancer, the author of an accompanying editorial wrote. Because the strength of the associations decreased -- but remained significant -- as genetic distance increased, "the associations are more likely mediated by shared genetic factors than by shared environmental factors."
"Shared environmental exposures are expected to affect only first-degree relatives because they generally live in the same house for part of their life and thus share air, water, food, and other environmental factors," wrote Walter Rocca, MD, of the Mayo Clinic in Rochester, Minn.
Despite limitations inherent to retrospective analyses and lack of definitive information on cause of death, the Utah study "led us to a higher vista point," Rocca added. "We have made one more step toward weaving several apparently conflicting observations from different lines of research into a coherent theory.
"Unfortunately, as is often the case in science, from this new higher vista point, we also see a broader horizon rich with new complexities and new challenges."
The study was supported by the Utah Cancer Registry, the Utah State Department of Health, and the University of Utah.
Cannon-Albright disclosed relationships with the Huntsman Cancer Foundation and the National Cancer Institute. One or more co-authors disclosed relationships with the Noorda Foundation, the National Institute of Neurological Disorders and Stroke, and Athena Diagnostics.
Rocca had no disclosures.
- Reviewed by Dori F. Zaleznik, MD Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, BSN, RN, Nurse Planner
Archives of NeurologySource Reference: Kareus SA, et al "Shared predispositions of Parkinsonism and cancer. A population-based pedigree-linked study" Arch Neurol 2012; DOI:10.1001/archneurol.2012.2261.
Archives of NeurologySource Reference: Rocca WA "Families with Parkinson disease and cancer" Arch Neurol 2012; DOI:10.1001/archneurol.2012.2664.